105年會論文摘要集 by Endo 電子書上傳區

Contents

Floor Plan of Conference Rooms........................................................................... 3

Daily Program Schedule.......................................................................................... 4

Opening Remarks..................................................................................................... 6

Board of Directors..................................................................................................... 8

Sponsors.................................................................................................................... 9

Agenda...................................................................................................................... 10

CV & Abstract: Plenary Lecture New Developments in Cushing’s Syndrome............................................................ 38

DAROC-TADE Joint Symposium 2016 Taiwan Diabetes Prevention, Treatment and Prospect of a New Realm........ 42

Symposium-1 The International Voice............................................................................................ 50

Symposium-2 Bone Metabolism & Osteoporosis Symposium........................................................ 56

Symposium-3 Adrenal Symposium................................................................................................. 62

Symposium-4 Thyroid Symposium................................................................................................. 70

Symposium-5 ESROC-KES Joint Symposium............................................................................... 76

Educational Lecture-1 Gender and Medicine.............................................................................................. 84

Education Lecture-2 Iodine Nutrition in Taiwan......................................................................................... 86

Oral Presentation-2................................................................................................. 88 Poster Presentation................................................................................................ 98 2016 Award............................................................................................................. 139

Floor Plan of Conference Rooms

The

th Annual Meeting of March 19-20, 2016 The Endocrine Society and The Diabetes Association of the R.O.C. (Taiwan)

37th Annual Meeting of The Endocrine Society and The Diabetes Association of the R.O.C. (Taiwan) Date: 19-20 March 2016 / Venue: Taipei Veterans General Hospital

Program March 19, 2016 (Sat) Time

08:55-12:00

1st

Conference Room

3rd

Conference Room

4th

MSD

LS-2

AstraZeneca

LS-3

Takeda

Sym-1

13:10-14:40

The International Voice

14:40-15:10

Coffee Break / Group Picture Oral-1

15:10-16:10

International Speech Contest Sym-2

16:10-17:00

17:00-17:30

Bone Metabolism & Osteoporosis Sym

Educational lecture-1

Gender and Medicine Educational lecture-2

Iodine Nutrition

17:30-17:40 18:30-20:30

Conference Room

DAROC-TADE Joint Sym LS-1

12:00-13:00

2nd

The Welcome Dinner / Caesar Park Taipei 4F

LS-4

Abbott

Daily Program Schedule

March 20, 2016 (Sun) Time

1st

Conference Room

2nd

Conference Room

3rd

Conference Room

4th

Conference Room BS-1

08:30-09:30

Bayer Diabetes Care Plenary Lecture

09:30-10:20

Cushing’s Syndrome

10:20-10:30 10:30-11:20 11:20-12:00

Coffee Break Political Presentation

Video Connection

General Assembly Video Connection LS-5

12:10-13:10

Video Connection

Boehringer Ingelheim / Lilly

LS-6

Adrenal Sym

15:00-15:30

Novartis

Sym-5

ESROC-KES Joint Sym Coffee Break

Sym-4

15:30-17:00

LS-8

Break Sym-3

13:30-15:00

Eli Lilly Company (Taiwan)

Novo Nordisk

13:10-13:30

LS-7

Thyroid Sym

Oral-2

Oral Presentation Members

The

th Annual Meeting of March 19-20, 2016 The Endocrine Society and The Diabetes Association of the R.O.C. (Taiwan)

理事長致詞各位會員女士先生、各位來賓：歡迎大家來到台北榮民總醫院致德樓參加中華民國內分泌暨糖尿病學會第 13 屆第 1 次會員大會暨學術研討會。有關國內學術活動方面，本會 104 年 5 月 23-24 日於劍潭青年活動中心，舉辦「104 年度內分泌新陳代謝專科醫師訓練課程」；104 年 7 月 11 日於苗栗頭份為恭醫院舉辦「104 年度經典病例討論會」；104 年 7 月 23 日於台大醫院人文博物館，召開「台灣肢端肥大症登記期末報告說明會及記者會」；104 年 11 月 15 日於高雄榮民總醫院，舉辦「Post SICEM」研討會，會員均踴躍出席！有關國際學術活動方面，本會 104 年 12 月 12-13 日於台大醫院國際會議中心，舉辦「2015 年內分泌繼續教育暨第 9 屆華夏內分泌大會」。出席人數：台灣 339 位（會員 331 位、非會員 8 位）、大陸 131 位、香港 10 位，共計 480 位參加。並發行「甲狀腺疾病最新進展」，廣獲與會大眾好評！同時亦積極參加國際學術活動，4/30-5/3 由本人代表參加內分泌學會姊妹會韓國內分泌學會（Korean Endocrine Society）「2015 年首爾國際內分泌新陳代謝大會暨第 34 屆韓國內分學會年度學術研討會（2015 SICEM）」；8/26-29 於大陸南京出席「中華醫學會第 14 次全國內分泌學術會議（CSE）」；8/26-27 由本人及黃天祥常務理事共同代表，於大陸南京參加「第 17 屆國際內分泌大會暨中華醫學會第 15 次全國內分泌學術會議之主要節目委員會（ICE/CSE 2016-Main POC Meeting）」；於美國奧蘭多參加「AOTA（Asia Oceania Thyroid Association）」會員大會及理監事會。期待能於國際發聲，並促進內分泌新陳代謝領域之學術交流！ 105/8/31-9/4 將於北京舉行「第 17 屆國際內分泌大會暨中華醫學會第 15 次全國內分泌學術會議（ICE/CSE 2016）」，希望會員踴躍報名參加。本次大會將選舉第 13 屆理監事。在此，感謝第 12 屆全體理監事過去三年來對學會的協助與支持。最後，感謝協辦單位贊助經費。並祝福各位會員身體健康，本次年會圓滿成功！中華民國內分泌學會理事長謹上 105 年 3 月 19 日 6

Opening Remarks

理事長致詞各位會員女士、先生您好：歡迎各位會員女士先生來參加中華民國內分泌暨糖尿病學會第 13 屆第 1 次會員大會暨學術研討會！每年我們相聚在此，分享經驗，同時邀請國內外內分泌與糖尿病知名的專家學者演講，獲得更多更新的醫療知識及技術。本屆理監事在今年屆滿，在過去三年中，為了培養年輕內分泌新陳代謝科專科醫師及增進會員交流，糖尿病學會積極舉辦課程；持續辦理 ADA 論文發表補助，每年徵求年輕會員之糖尿病研究計畫獎勵；出版 2015 糖尿病臨床照護指引，舉辦多場糖尿病治療指引推廣研討會；為了瞭解糖尿病在台灣現況，我們邀請全台灣約 100 家糖尿病健康促進機構進行「台灣糖尿病登錄計畫」，此登錄系統可讓醫療人員了解病患疾病狀態，提供台灣日後糖尿病治療照護與研究等之重要參考依據；為減少健保核刪的爭議，本學會也建置健保申覆案件 template，提供會員們參閱使用；而在每年 11 月聯合國世界糖尿病日，學會也積極參與，並與糖尿病衛教學會輪流主辦，2015 年與南投縣政府衛生局合作，在日月潭文武廟舉辦聯合國世界糖尿病日嘉年華及點燈活動，其活動照片刊登在 IDF WDD 官方刊物，為台灣爭光；這些努力讓糖尿病學會得到內政部肯定，榮獲 103 年度全國性社會暨職業團體績效評鑑之優等團體，這是所有會員、理監事們與正副秘書長及會務同仁努力的成果與榮耀。為了讓學會永續經營服務會員，在 2015 年購買了學會永久會址，我們將持續臨床照護教育、鼓勵學術研究與強化人員訓練，加強與其它相關學會之交流，提升本學會對國內衛生與健保政策制定等之影響力，更與國外 ( 亞太地區 ) 各糖尿病學會，進行研究與人員交流訓練，提升本學會國際能見度。最後，歡迎會員踴躍參與今年，也就是 2016 年 10 月 27-30 日於台北國際會議中心舉行 11th IDF-WPR Congress & 8th AASD Scientific Meeting，糖尿病學會與糖尿病衛教學會等共同舉辦，目前積極籌備中，將邀請世界各國糖尿病專家來台演說，同時全球糖尿病菁英也將聚焦於此，來台交流。大會目前已開放投稿，衷心期盼您能參與這盛會。敬祝大家身體健康，大會圓滿成功。社團法人中華民國糖尿病學會理事長謹上 105 年 3 月 19 日 7

The

th Annual Meeting of March 19-20, 2016 The Endocrine Society and The Diabetes Association of the R.O.C. (Taiwan)

Board of Directors

（依照姓氏筆劃排序）

The Endocrine Society of the Republic of China(Taiwan) President

葉振聲 Tjin-Shing Jap

Standing Executive Board

翁錦興 Ging-Shing Won

黃天祥 Tien-Shang Huang

Executive Board

王佩文 Pei-Wen Wang 王治元 Chih-Yuan Wang 李亭儀 Annie Lee 張慶忠 Ching-Chung Chang

曾芬郁 Fen-Yu Tseng 蔡克嵩 Keh-Sung Tsai 鄧錦泉 Kam-Tsun Tang 簡銘男 Ming-Nan Chien

Standing Control Board

林仁德 Jen-Der Lin

Control Board

林宏達 Hong-Da Lin

Secretary General

陳涵栩 Harn-Shen Chen

Secretary

林亮羽 Liang-Yu Lin 林慶齡 Cheering Lin 林興中 Hing- Chung Lam 劉鳳炫 Feng Hsuan Liu

張天鈞 Tien-Chun Chang

郭錦松 Chin-Sung Kuo 陳雁玲 Yan-Ling Chen 黃建寧 Chien-Ning Huang

The Diabetes Association of the Republic of China(Taiwan) President

許惠恒 Wayne Huey-Herng Sheu

Standing Executive Board

蔡世澤 Shih-Tzer Tsai

陳榮福 Jung-Fu Chen

Executive Board

江怡德 Yi-Der Jiang 杜思德 Shih-Te Tu 胡啟民 Chii-Min Hwu 莊峻鍠 Jyuhn-Huarng Juang

郭清輝 Ching-Fai Kwok 黃禹堯 Yu-Yao Huang 裴馰 Dee Pei 謝明家 Ming-Chia Hsieh

Standing Control Board

莊立民 Lee-Ming Chuang

Control Board

何橈通 Low-Tone Ho

Secretary General

林時逸 Shih-Yi Lin

Secretary

王俊興 Jun-Sing Wang 朱志勳 Chih-Hsun Chu 李弘元 Hung-Yuan Li

戴東原 Tong-Yuan Tai

李奕德 I-Te Lee 林昆德 Kun-Der Lin 洪乙仁 Yi-Jen Hung

Sponsors

The Endocrine Society and The Diabetes Association of the R.O.C. (Taiwan) Would Like to Recognize the Following for Their Support of the 37th Annual Meeting 1

臺灣阿斯特捷利康股份有限公司 AstraZeneca Taiwan Limited

台灣百靈佳殷格翰股份有限公司 Boehringer Ingelheim Taiwan Limited

台灣諾和諾德藥品股份有限公司 Novo Nordisk Pharma (Taiwan) Ltd.

台灣禮來股份有限公司 Eli Lilly Company (Taiwan)

台灣諾華股份有限公司 Novartis (Taiwan) Co., Ltd.

美商默沙東藥廠股份有限公司 Merck Sharp & Dohme (I.A)LLC Taiwan Branch

台灣拜耳股份有限公司 Bayer Taiwan Co., Ltd.

台灣武田藥品工業股份有限公司 Takeda Pharmaceuticals Taiwan, Ltd.

美商亞培股份有限公司 Abbott Laboratories Services Corp., Taiwan Branch

台灣安斯泰來製藥股份有限公司 Astellas Pharma Taiwan, Inc.

友華生技醫藥股份有限公司 Orient EuroPharma Co., Ltd.

台灣羅氏醫療診斷設備股份有限公司 Roche Diagnostics Ltd., Taiwan

安克生醫股份有限公司 ( 美吾華懷特生技集團 )AmCad BioMed Corporation

嘉德藥品企業股份有限公司 Char Deh Drugs Enterprise Co.,Ltd

台灣拜耳股份有限公司 Bayer Taiwan Co., Ltd.

台灣田邊製藥股份有限公司 Taiwan Tanabe Seiyaku Co., Ltd.

賽諾菲股份有限公司 Sanofi Taiwan Co. Ltd.

科懋生技股份有限公司 Excelsior Biopharma Inc.

美敦力醫產品股份有限公司 Medtronic (Taiwan) Ltd.

東研實業股份有限公司 Tunyen Enterprise Corporation

力大圖書 The Leader Book Company Ltd. 9

The

th Annual Meeting of March 19-20, 2016 The Endocrine Society and The Diabetes Association of the R.O.C. (Taiwan)

March 20, 2016 (Sun) 【1st Conference Room】

Plenary Lecture Cushing’s Syndrome Moderator: Hong-Da Lin

09:30-10:20

New Developments in Cushing’s Syndrome ANDRE LACROIX (CANADA) Professor of Medicine, Division of Endocrinology, Centre hospitalier de l’Université de Montréal (CHUM).

March19, 2016 (Sat) 【1st Conference Room】

8:55-9:00

DAROC-TADE Joint Symposium 2016 Taiwan Diabetes Prevention, Treatment and Prospect of a New Realm Opening SHIH-TE TU President, Taiwanese Association of Diabetes Educators Division of Endocrinology and Metabolism, Lukang Christian Hospital

Moderator: Jung-Fu Chen 9:00-9:40

DT-1

IDF Diabetes Atlas 2015 and the Trends of Diabetes and Its Complications in Taiwan CHIN-HSIAO TSENG Department Internal Medicine, National Taiwan University College of Medicine, Taipei, Taiwan, ROC

Moderator: Yi-Jen Hung 9:40-10:20

DT-2

臺灣糖尿病之現況及展望 SHU-TI CHIOU Director-General, Health Promotion Administration, Ministry of Health and Welfare

10:20-10:30 10

Break

Agenda Moderator: Sih-Yu Chen 10:30-11:10

DT-3

The Current and Future Prospects of Continuous Glucose Monitoring System (CGMS) in Diabetes Care I-CHIEH MAO Department of Endocrinology and Metabolism, Lukang Christian Hospital, Changhua County, Taiwan, ROC

Moderator: Chih-Yuan Wang 11:10-11:50

DT-4

Trend and Factors Associated with Healthcare Use and Costs in Type 2 Diabetes Mellitus: A Decade Experience of a Universal Health Insurance Program CHIH-CHENG HSU Institute of Population Health Science, National Health Research Institutes, Zhunan, Taiwan

11:50-12:00

Discussion

March 19, 2016 (Sat) 【1st Conference Room】

Symposium-1 The International Voice Moderator: Annie Lee, Jen-Der Lin

13:10-13:15

Opening TJIN-SHING JAP President, The Endocrine Society of the R.O.C. (Taiwan) Division of Endocrinology and Metabolism, Taipei Veterans General Hospital

13:15-13:35

S1-1

The NIH-UST- ASIAN Collaboration LEILANI B. MERCADO-ASIS (THE PHILIPPINES) Internal Medicine, University of Santo Tomas, Manila, Philippines

13:35-13:55

S1-2

The Present and Future of Endocrinology in Thailand YUPIN BENJASURATWONG (THAILAND) First Vice President, The Endocrine Society of Thailand Division of Endocrinology and Metabolism, Department of Medicine, Phramongkutklao College of Medicine, Bangkok, Thailand.

The

th Annual Meeting of March 19-20, 2016 The Endocrine Society and The Diabetes Association of the R.O.C. (Taiwan)

13:55-14:15

S1-3

Successful Organization of an International Medical Conference JOSEPH LOPEZ (MALAYSIA) APFCB Immediate Past President and Chair, APFCB Congresses and Conferences Committee

14:15-14:35

Discussion

14:35-14:40

Closing WAYNE HUEY-HERNG SHEU President, The Diabetes Association of the R.O.C. (Taiwan) Division of Endocrinology and Metabolism, Taichung Veterans General Hospital

March 19, 2016 (Sat) 【1st Conference Room】

Symposium-2 Bone Metabolism & Osteoporosis Symposium Moderator: Keh-Sung Tsai, Ching-Chung Chang

16:10-16:35

S2-1

Role of Active Vitamin D Compounds in the Treatment of Osteoporosis TOSHIO MATSUMOTO (JAPAN) Fujii Memorial Institute of Medical Sciences, University of Tokushima, Tokushima, Japan

16:35-17:00

S2-2

Is It Osteoporosis? SIOK BEE CHIONH (SINGAPORE) Division of Endocrinology, National University Hospital

17:00-17:25

S2-3

Diabetes and Osteoporosis JUNG-FU CHEN (TAIWAN) Department of Endocrinology and Metabolism, Kaohsiung Chang Gung Memorial Hospital

17:25-17:40 12

Discussion

Agenda March 20, 2016 (Sun) 【1st Conference Room】

Symposium-3 Adrenal Symposium Moderator: Ging-Shing Won, André Lacroix

13:30-13:55

S3-1

Primary Aldosteronism: Unilateral or Bilateral Disease? ANDRÉ LACROIX (CANADA) Professor of Medicine, Division of Endocrinology, Centre hospitalier de l’Université de Montréal (CHUM).

13:55-14:20

S3-2

Patients Who have Taught Me a Lot: Personal Experiences of Rare Adrenal Diseases SIHOON LEE (KOREA) Department of Internal Medicine/Endo and Laboratory of Genomic and Translational Medicine, Gachon University School of Medicine, Incheon, Korea Department of Bioengineering, Graduate School of Engineering, The University of Tokyo, Tokyo, Japan

14:20-14:45

S3-3

Clinical and Genetic Heterogeneity of AldosteroneProducing Adenoma in Taiwan SHIH-HUA LIN (TAIWAN) Department of Medicine, Division of Nephrology, Tri-Service General Hospital, Taipei, Taiwan, ROC

14:45-15:00

Discussion

The

th Annual Meeting of March 19-20, 2016 The Endocrine Society and The Diabetes Association of the R.O.C. (Taiwan)

March 20, 2016 (Sun) 【1st Conference Room】

Symposium-4 Thyroid Symposium Moderator: Tien-Shang Huang, Tien-Chun Chang

15:30-15:55

S4-1

Rapid Responder Graves’ Thyrotoxicosis: Clinical Features, Clinical Implications KON YIN CHIAN, WINSTON (SINGAPORE) President, Endocrine and Metabolic Society of Singapore Senior Consultant, Dept of Endocrinology, Tan Tock Seng Hospital, Singapore

15:55-16:20

S4-2

Management of Radioactive Iodine-Refractory Differentiated Thyroid Carcinoma - Data from Kaohsiung Chang Gung Memorial Hospital PEI-WEN WANG (TAIWAN) Department of Internal Medicine and Nuclear Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan

16:20-16:45

S4-3

IgG4-Related Thyroid Diseases TAKASHI AKAMIZU (JAPAN) President, AOTA Vice President, Japan Endocrine Society President, Japan Thyroid Association The First Department of Medicine, Wakayama Medical University, Japan

16:45-17:00

Discussion

Agenda March 20, 2016 (Sun) 【2nd Conference Room】

Symposium-5 ESROC-KES Joint Symposium Moderator: Young Kee Shong, Tjin-Shing Jap

13:30-13:50

S5-1

Drug-Induced Thyroid Dysfunctions LIANG-YU LIN (TAIWAN) Division of Endocrinology and Metabolism, Taipei Veterans General Hospital

13:50-14:10

S5-2

Type 2 Diabetes Mellitus and Osteoporosis YOON-SOK CHUNG (KOREA) Department of Endocrinology and Metabolism, Ajou University School of Medicine, Suwon, South Korea

14:10-14:30

S5-3

Alpha Lipoic Acid Inhibits Proliferation and EpithelialMesenchymal Transition of Thyroid Cancer Cells WON BAE KIM (KOREA) Department of Internal Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea

14:30-14:50

S5-4

Impact of 18F-FDG PET/CT on the Clinical Outcome and Management of Differentiated Thyroid Cancer Patients with Positive 131I Whole Body Scan and Elevated Thyroglobulin YEN-HSIANG CHANG (TAIWAN) Department of Nuclear Medicine, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung City, Taiwan, ROC

14:50-15:00

Discussion

The

th Annual Meeting of March 19-20, 2016 The Endocrine Society and The Diabetes Association of the R.O.C. (Taiwan)

March 19, 2016 (Sat) 【2nd Conference Room】

Educational Lecture-1 Gender and Medicine Moderator: Feng Hsuan Liu

16:10-17:00

EL-1

Gender and Medicine CHIOU-FEN LIN (TAIWAN) School of Nursing, National Taipei University of Nursing and Health Sciences Department of Nursing, Shuang Ho Hospital, Taipei Medical University

March 19, 2016 (Sat) 【2nd Conference Room】

Education Lecture-2 Iodine Nutrition in Taiwan Moderator: Kam-Tsun Tang

17:00-17:20

EL-2

Assessment and Interpretation of Iodine Nutrition of Populations: Experiences from the Recent Taiwan Surveys FAN-FEN WANG (TAIWAN) Division of Endocrinology and Metabolism, Yang-Ming Branch, Taipei City Hospital, Taipei, Taiwan, ROC

17:20-17:30

Discussion

Agenda March 19, 2016 (Sat) 【1st Conference Room】

Oral Presentation-1 International Speech Contest Contest Chair: Lawrence Huang

15:10-15:15

Opening TJIN-SHING JAP President, The Endocrine Society of the R.O.C. (Taiwan) Division of Endocrinology and Metabolism, Taipei Veterans General Hospital

O1-1 ～

15:15-16:10

O1-6

My Experience in Endocrine Research HYEMI KWON (KOREA)

My Inspiration in Endocrinology Discuss with the Contest Chair to determine the order of speech

CHONPITI SIRIWAN (THAILAND)

Young and Navie CHI-HO LEE (HONG KONG)

An Unforgettable Case of Adrenocortical Carcinoma CHUN-JUI HUANG (TAIWAN)

It’s Not The Same Without Sugar MARC GREGORY Y. YU (THE PHILIPPINES)

Snake Bite Induced Hypopituitarism AUNG KYAW MYO (MYANMAR)

The

th Annual Meeting of March 19-20, 2016 The Endocrine Society and The Diabetes Association of the R.O.C. (Taiwan)

March 20, 2016 (Sun) 【2nd Conference Room】

Oral Presentation-2 Moderator: Fen-Yu Tseng, Ming-Nan Chien

15:30~15:40

O2-1

DIETARY INTAKE IN ELDERLY TYPE 2 DIABETES SUBJECTS IN TAIWAN 1

HSIU-YUEH SU, 2MIN-SU TZENG, 3SHU-TI CHIOU, 4 NENG-CHUN YU, 5WAYNE H-H SHEU 1

Department of Dietetics, Taipei Medical University Hospital, Taipei, Taiwan, ROC;2Department of Nutritional Science, Fu Jen Catholic University, Taipei, Taiwan, ROC;3Health Promotion Administration, Ministry of Health and Welfare, Taiwan, ROC;4Yu Neng-Chun Diabetes Clinic, I-Lan County, Taiwan, ROC;5Division of Endocrinology and Metabolism, Department of Internal Medicine, Taichung Veterans General Hospital, Taichung, Taiwan, ROC

15:40~15:50

O2-2

S ITAGLIPTIN AND RISK OF HEART FAILURE HOSPITALIZATION IN PATIENTS WITH TYPE 2 DIABETES AND END STAGE RENAL DISEASE ON DIALYSIS: A POPULATION-BASED COHORT STUDY 1,2

YI-CHIH HUNG, 3,4CHE-CHEN LIN, 1,2 WEI-LUN HUANG, 5MAN-PING CHANG, 1,6 CHING-CHU CHEN 1

Division of Endocrinology and Metabolism, Department of Medicine, China Medical University Hospital, Taichung, Taiwan, R.O.C.; 2 BDepartment of Medicine, China Medical University, Taichung, Taiwan, R.O.C.;3Management Office for Health Data, China Medical University Hospital, Taichung, Taiwan, R.O.C.;4Department of Public Health, China Medical University, Taichung, Taiwan, R.O.C.;5Department of Nursing, School of Health, National Taichung University of Science and Technology, Taichung, Taiwan, R.O.C.;6School of Chinese Medicine, China Medical University, Taichung, Taiwan, R.O.C.

Agenda 15:50~16:00

O2-3

ALTERED MITOCHONDRIAL DYNAMICS, BIOGENESIS, AND BIOENERGETICS IN CYBRID CELLS HARBORING A DIABETES-SUSCEPTIBLE MITOCHONDRIAL DNA HAPLOGROUP 1

CHENG-FENG TSAO, 1PEI-WEN WANG, 1 HSIAO-MEI KUO, 1SHAO-WEN WENG, 3 JIIN-HAUR CHUANG, 2TSU-KUNG LIN, 2 CHIA-WEI LIOU, 1CHING-YI LIN 1

Department of Internal Medicine, 2Department of Neurology and Department of Surgery , Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung 833, Taiwan 3

16:00~16:10

O2-4

NONFUNCTIONAL PITUITARY MACROADENOMA WITH PANHYPOPITUITARISM AND HYPONATREMIA— REPORT OF TWO CASES WEI-HSIN HSU, I-MIN PAN Division of Endocrinology and Metabolism, Tainan Sin-Lau Hospital, Tainan, Taiwan, R.O.C.

16:10~16:20

O2-5

RETROSPECTIVE ANALYSIS OF DIABETIC KETOACIDOSIS TREATMENT WITH MODIFIED AND SIMPLIFIED REGIMEN: A MEDICAL CENTER EXPERIENCE SENG-WEI OOI, HUA-FEN CHEN Department of Metabolism, Far Eastern Memorial Hospital, Taipei, Taiwan.

16:20~16:30

O2-6

CLINICAL CHARACTER OF PAPILLARY THYROID CANCER WITH HYPERTHYROIDISM WEI-YU CHOU, SZU-TAH CHEN, JEN-DER LIN Division of Endocrinology and Metabolism, Department of Internal Medicine, Chang Gung Memorial Hospital, Chang Gung University, Taiwan, R.O.C.

The

th Annual Meeting of March 19-20, 2016 The Endocrine Society and The Diabetes Association of the R.O.C. (Taiwan)

16:30~16:40

O2-7

COMPARISON OF CLINICAL CHARACTERISTICS AND OUTCOME OF MICRO- AND MACROALBUMINURIA IN TYPE 2 DIABETES WAI-KIN CHAN, SZU-TAH CHEN Division of Endocrinology and Metabolism, Department of Internal Medicine, Chang Gung Memorial Hospital, Chang Gung University, Taiwan, R.O.C

16:40~16:50

O2-8

INTERACTION BETWEEN STRA6 SIGNALING SUPPRESSION AND MITOCHONDRIAL DYSFUNCTION INDUCES KIDNEY APOPTOSIS AND FIBROSIS IN DIABETES 1

CHAO-HUNG CHEN, 2KUN-DER LIN, 3 TUSTY-JIUAN HSIEH, 2YU-LI LEE, 2MEI-YUEH LEE, 2,4 PI-JUNG HSIAO, 2,4SHYI-JANG SHIN 1

Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, 80708, Taiwan;2Division of Endocrinology and Metabolism, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, 80708, Taiwan;3Department of Medical Genetics, School of Medicine, College of Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, 80708, Taiwan;4Department of Internal Medicine, School of Medicine, College of Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, 80708, Taiwan

16:50~17:00

O2-9

SULFONYLUREA THERAPY IMPROVED DIABETIC CONTROL IN A MAN WITH NEONATAL DIABETES AND AN ACTIVATING KCNJ11 MUTATION 1,2,3,4,5

YANN-JINN LEE, 1,6CHI-YI HUANG, 1,6 WEI-HSIN TING, 2CHIUNG-LING LIN, 1CHON-IN CHAN 1

Department of Pediatric Endocrinology, MacKay Children’s Hospital; Department of Medical Research, MacKay Memorial Hospital Tamsui District; 3Department of Pediatrics, School of Medicine, College of Medicine, Taipei Medical University; 4Institute of Biomedical Sciences, MacKay Medical College; 5Department of Medicine, MacKay Medical College; 6Department of Nursing, MacKay Medicine, Nursing and Management College 2

Agenda March 19,2016 (Sat) 09:00 -March 20, 2016(Sun)16:00

Poster Presentation

【The Gallery Outside the 3rd & 4th Conference Room】 PP-01

A YOUNG ADULT WOMAN WITH SEVERE OSTEOPOROSIS DUE TO CUSHING’S DISEASE YAN-RONG LI, CHIH-YIU TSAI, CHENG-WEI LIN, SZU-TAH CHEN, JEN-DER LIN, JAWL-SHAN HWANG Division of Endocrinology and Metabolism, Department of Internal Medicine, Linkou Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Taiwan, R.O.C.

PP-02

AN ADRENAL ONCOCYTOMA PRESENTING AS CUSHING’S SYNDROME: CASE REPORT AND LITERATURE REVIEW 1

CHIN CHOU YANG, 2CHENG HO CHUNG, 3 CHIUNG MING HSU, 4TAO YUAN WANG, 5PEI SHAN TSAI 1

Division of Endocrinology and Metabolism, Mackay Memorial Hospital, Hsinchu, Taiwan;2Division of Endocrinology and Metabolism, Mackay Memorial Hospital, Taiwan;3Department of Urology, Mackay Memorial Hospital, Taiwan;4Department of Pathology, Mackay Memorial Hospital, Taiwan;5Department of Radiology, Mackay Memorial Hospital, Taiwan

PP-03

A CASE OF ISOLATED HYPOGONADOTROPIC HYPOGONADISM WITH PARTIAL EMPTY SELLA FOLLOWING NORMAL COURSE OF PREGNANCY AND DELIVERY. 1

SHUN-HUO WANG, 2KUNG-YU WANG, 1 CHIH-YUAN WANG 1

Division of Endocrinology and Metabolism, Department of Internal Medicine, National Taiwan University Hospital, Taiwan, R.O.C.; 2 Department of Internal Medicine, National Taiwan University Hospital, Taiwan, R.O.C.

The

th Annual Meeting of March 19-20, 2016 The Endocrine Society and The Diabetes Association of the R.O.C. (Taiwan)

PP-04

LY2963016 INSULIN GLARGINE VS LANTUS® INSULIN GLARGINE IN TYPE 2 DIABETES MELLITUS: EAST ASIAN SUBGROUP OF ELEMENT-2 1

CHING-CHU CHEN, 2JU-FEN YEH, 3DAI CHIDA, 4 JACEK KILJANSKI, 5LIZA ILAG, 5ROBYN POLLOM, 5 DACHUANG CAO, 6KYUNG WAN MIN 1

Division of Endocrinology and Metabolism, Department of Medicine, China Medical University Hospital, Taichung, Taiwan; 2Eli Lilly, Taipei, Taiwan; 3 Eli Lilly Japan K.K., Tokyo, Japan; 4Eli Lilly, Warsaw, Poland; 5Eli Lilly and Company, Indianapolis, USA; 6Eulji General Hospital, Seoul, South Korea

PP-05

THYROTOXIC NEUROPATHY: REPORT OF A CASE 1

SHIH-CHE HUA, 2PO-YEN YEH

Division of Endocrinology and Metabolism, Department of Internal Medicine, St. Martin De Porres Hospital, Taiwan;2Division of Neurology, Department of Internal Medicine, St. Martin De Porres Hospital, Taiwan

PP-06

PRIMARY SQUAMOUS CELL CARCINOMA OF THYROID: A CASE REPORT 1

HUNG-YI HUANG, 2SHIH-PING CHENG

Division of Endocrinology and Metabolism, Department of Internal Medicine, MacKay Memorial Hospital, Taiwan, R.O.C.; 2Department of General Surgery, MacKay Memorial Hospital, Taiwan, R.O.C

PP-07

GLIMEPIRIDE-INDUCED HEMOLYTIC ANEMIA IN A GLUCOSE-6-PHOSPHATE DEHYDROGENASE(G6PD) DEFICIENT PATIENT: A CASE REPORT AND LITERATURE REVIEW CHUN-TA HUANG Division of Endocrinology and Metabolism, Department of Internal Medicine, Mackay Memorial Hospital, Taipei Branch, Taiwan, R.O.C.

Agenda PP-08

POORLY CONTROLLED HYPERTENSION IN A CASE WITH 17-Α HYDROXYLASE DEFICIENCY 1

YIN-HUEI CHEN, 1ZI-YUAN WANG, 2YEN-NIEN LIN, 1 CHING-CHU CHEN, 1CHING-CHUNG CHANG, 1 YI-CHIN HUNG 1

Division of Endocrinology and Metabolism, Department of Internal Medicine, China Medical University Hospital, Taiwan, R.O.C.;2Division of Cardiology, Department of Internal Medicine, China Medical University Hospital, Taiwan, R.O.C.

PP-09

ACUTE APPENDICITIS: A RARE PRESENTATION OF ANTI-THYROID DRUG INDUCED AGRANULOCYTOSIS YI-CHEN WU, RONG LIN Division of Endocrinology and Metabolism, Department of Internal Medicine,Far Eastern Memorial Hospital, Taiwan, R.O.C.

PP-10

CASE REPORT: CONGENITAL ADRENAL HYPERPLASIA, 21 ALPHA-HYDROXYLASE DEFICIENCY, SALT-WASTING TYPE 1

CHIN-FAN CHEN, 2CHI-YU HUANG, 2YANN-JINN LEE, 2 WEI-HSIN TING, 3CHAO-HUNG WANG, 3 MING-NAN CHIEN, 1YA-CHUN HSIAO 1

Division of Endocrinology and Metabolism, Mackay Memorial Hospital,Hsinchu City, Taiwan, ROC.;2Division of Pediatric Endocrinology and Metabolism, Mackay Memorial Hospital, Taipei, Taiwan, ROC;3Division of Endocrinology and Metabolism, Mackay Memorial Hospital, Taipei, Taiwan, ROC.

PP-11

LARGE BILATERAL ADRENAL MASS IN A 43-YEAROLD MAN: A CASE REPORT SHIHCHANG LO, EDY KORNELIUS, CHIEN NING HUANG Division of Endocrinology and Metabolism, Department of Internal Medicine, Chung Shan Medical University Hospital, Taichung, Taiwan

The

th Annual Meeting of March 19-20, 2016 The Endocrine Society and The Diabetes Association of the R.O.C. (Taiwan)

PP-12

25 Years Old Man with Central Diabetes Insipidus 1,2

Bao-Mei Wang, 1,2,3Ching-Chieh Su

Department of Internal Medicine, Cardinal Tien Hospital, Xindian, New Taipei City, Taiwan; 2Division of Endocrinology, Department of Internal Medicine, Cardinal Tien Hospital, Xindian, New Taipei City, Taiwan; 3 School of Medicine, Fu-Jen Catholic University, New Taipei City, Taiwan

PP-13

DIABETIC KETOACIDOSIS AS THE INITIAL PRESENTATION OF ACROMEGALY 1

YUNG-HSIN TSAI, 1,2SHYANG-RONG SHIH

Division of Endocrinology and Metabolism, Department of Internal Medicine, National Taiwan University Hospital, National Taiwan University, Taipei, Taiwan, R.O.C.;2Department of Medicine, College of Medicine, National Taiwan University, Taipei, Taiwan, R.O.C

PP-14

SEVERE SYMPTOMATIC HYPERCALCEMIA - CHRONIC TOPHACEOUS GOUT AS THE POSSIBLE TRIGGER? 1

CHEN-TI WANG, 1, 2YUNG-CHUAN LU, 1YU-HSI KAO, 1 SHU-JU KU, 1KUO-BIN TSENG 1

Division of Endocrinology and Metabolism, Department of Internal Medicine, E-DA Hospital, Kaohsiung, Taiwan; 2 School of Medicine for International Students, I-Shou University College of Medicine, Kaohsiung, Taiwan

PP-15

PITUITARY STALK LESION WITH PARTIAL CENTRAL DIABETES INSIPIDUS-A CASE REPORT 1

YIN-HUEI CHEN, 1RONG-HSING CHEN, 2YEN-NIEN LIN, 1CHING-CHUNG CHANG 1

Division of Endocrinology and Metabolism, Department of Internal Medicine, China Medical Univetsity Hospital; 2Division of Cardiology , Department of Internal Medicine, China Medical Univetsity Hospital

Agenda PP-16

ACUTE ENLARGING GOITER AFTER INTRAVENOUS THROMBOLYSIS FOR SEVERE DEEP VEIN THROMBOSIS 1

YIN-HUEI CHEN, 1CHING-CHU CHEN, 1 CHING-CHUNG CHANG, 1CHWEN-TZUEI CHANG, 2 YEN-NIEN LIN, 2CHIUNG-RAY LU 1

Division of Endocrinology and Metabolism, Department of Internal Medicine, China Medical University Hospital; 2.Division of Cardiology , Department of Internal Medicine, China Medical University Hospital

PP-17

A NEWLY ONSET DIABETES PRESENTING WITH DKA DUE TO GAS-FORMING PYOGENIC LIVER ABSCESS COMPLICATED WITH PNEUMOPERITONEUM JUIHSIANG LI, CHI CHAO WANG Tao-Yuan General Hospital

PP-18

GLUCOSE HOMEOSTASIS DURING ACUTE EXPOSURE TO HIGH ALTITUDES: PERSONAL EXPERIENCE IN SOUTH AMERICA CHUN-TING YEH, NAI-CHENG YEH, FENG- CHIEH YEN, KAI-JEN TIEN, CHWEN-YI YANG Division of Endocrinology and Metabolism, Department of Internal Medicine, Chi Mei Medical Center

PP-19

WHAT NEXT IN PATIENTS WITH TYPE 2 DIABETES MELLITUS INADEQUATELY CONTROLLED WITH METFORMIN AND SULFONYLUREA? PIOGLITAZONE OR BASAL INSULIN?—FROM THE PERSPECTIVE OF RENAL FUNCTION CHANGE 1

YU-HUNG CHANG, 1DER-WEI HWU, 1KUN-CHEN LIN, 1 DAO-MING CHANG, 2LING-WANG AN, 3 CHANG-HSUN HSIEH, 1YAU-JIUNN LEE 1

Lee’s Endocrinology Clinic;2Beijing Ruijing Diabetes Hospital;3Division of Endocrinology and Metabolism, Department of Internal Medicine, National Defense Medical Center, Tri-Service General Hospital, Taipei, Taiwan

The

th Annual Meeting of March 19-20, 2016 The Endocrine Society and The Diabetes Association of the R.O.C. (Taiwan)

PP-20

MEDULLARY THYROID CARCINOMA IN A PATIENT WITH HASHIMOTO’S THYROIDITIS 1

YU-CHUN HSUEH, 1,2TING-WEI LEE, 1,3TING-I LEE, 1 CHUN-JEN CHANG, 1YU-MEI CHIEN, 1CHI FAN

Division of Endocrinology and Metabolism, Taipei Medical UniversityWan Fang Hospital, Taipei, Taiwan 2 Graduate Institute of Clinical Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan 3 General Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan

PP-21

CLINICAL FEATURES OF METASTATIC NEUROENDOCRINE TUMOR OF THE THYROID GLAND 1

PO CHUNG CHENG, 1SHU YI WANG, 2TA-JEN WU

Division of Endocrinology and Metabolism, Department of Internal Medicine, Changhua Christian Hospital, Changhua County, Taiwan, R.O.C.

PP-22

CASE REPORT OF DM WITH TOES GANGREN WHICH WAS ASSOCIATED WITH UNUSUAL ETIOLOGY: MITOCHONDRIAL DISORDER WEI-TSEN LIAO, MING-CHIEH TSAI, CHUN-CHUAN LEE Division of Endocrinology & Metabolism, Department of Internal Medicine, Mackay Memorial hospital, Taiwan, R.O.C.

PP-23

PROGNOSTIC MARKER OF DIABETIC NEPHROPATHY: A PILOT STUDY BY METABOLOMIC APPROACH 1 1

CHIEN-AN CHOU, 1SZU-TAH CHEN, 2CHIA-NI LIN

Division of Endocrinology and Metabolism, Department of Internal Medicine, Chang Gung Memorial Hospital, Chang Gung University, Taoyuan, Taiwan, ROC;2Department of Laboratory Medicine, Chang Gung Memorial Hospital Linkou Branch, Taoyuan, Taiwan

Agenda PP-24

THE BIOCHEMICAL VARIANT BETWEEN DIFFERENT GENDERS IN PEOPLE AGED 40 TO 50 YEARS WHO HAVE NON-ALCOHOLIC FATTY PANCREAS DISEASE (NAFPD) YI-HSUAN CHEN, CHIH-YUAN WANG Division of Endocrinology, Department of Internal Medicine, National Taiwan University, 7, Chung-Shan South Road, Taipei, Taiwan

PP-25

A COHORT STUDY ON TEN-YEAR SURVIVAL OF SPORADIC MEDULLARY THYROID CARCINOMA WITH SOMATIC RET MUTATION: A SINGLE CENTER EXPERIENCE 1

LI-LUN CHUANG, 3,8DAW-YANG HWANG, 4 KUN-BOW TSAI, 5,7HON-MAN CHAN, 6,7 FENG-YU CHIANG, 2,7PI-JUNG HSIAO 1

Division of Endocrinology and Metabolism, Kaohsiung Municipal CiJin Hospital;2Division of Endocrinology and Metabolism, Kaohsiung Medical University Hospital;3Division of Nephrology, Kaohsiung Medical University Hospital;4Department of Pathology, Kaohsiung Municipal Siaogang Hospital;5Department of Surgery, Kaohsiung Medical University Hospital;6Department of Otolaryngology-Head and Neck Surgery;7School of Medicine, College of Medicine, Kaohsiung Medical University;8Lipid Science and Aging Research Center, Kaohsiung Medical University

PP-26

RELATIONSHIP BETWEEN METABOLIC PARAMETERS AND TESTOSTERONE LEVEL IN MALE PATIENSTS WITH T2DM -A CROSSSECTION STUDY IN REGIONAL HOSPITAL 1

SHIH-MING CHUANG, 1MING-NAN CHIEN, 1 CHUN-CHUAN LEE, 2KAT-YIEN NGU 1

Division of Endocrinology and Metabolism, Department of Internal Medicine, Mackay Memorial Hospital, Taipei;2Division of Endocrinology and Metabolism, Department of Internal Medicine, Mackay Memorial Hospital, Taitung,

The

th Annual Meeting of March 19-20, 2016 The Endocrine Society and The Diabetes Association of the R.O.C. (Taiwan)

PP-27

HYPOGLYCEMIA AND INSULINOMA CHIH-HUANG CHIU, SHU-YI WANG Division of Endocrinology and Metabolism, Department of Internal Medicine, Changhua Christian Hospital, Changhua, Taiwan

PP-28

ACROMEGALY PRESENTING WITH NEWLYDIAGNOSED DIABETES MELLITUS: A CASE REPORT PO-WEN YANG Department of Internal Medicine, Keelung Hospital, Ministry of Health and Welfare, Taiwan, R.O.C.

PP-29

USE MODERN THERAPY IN A 69-YEAR-OLD COMPLICATED PATIENT WITH TYPE 2 DIABETES: A 2-YEAR EXPERIENCE SHENG-CHI SU Division of Endocrinology and Metabolism, Department of Internal Medicine, Jiannren Hospital, Taiwan, R.O.C.

PP-30

DIPEPTIDYL PEPTIDASE-4 INHIBITOR PREVENTS ARTERIAL DAMAGE THROUGH STRA6 SIGNALING BEYOND GLYCEMIC CONTROL IN HIGH FAT DIETFED MICE 1

CHAO-HUNG CHEN, 2HSING-YI LIN, 2 KUN-DER LIN, 2MEI-YUEH LEE, 2YU-LI LEE, 2 WEI-WEN HUNG, 2HE-JIUN JIANG, 2,3PI-JUNG HSIAO, 2,3 SHYI-JANG SHIN 1

Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, 80708, Taiwan;2Division of Endocrinology and Metabolism, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, 80708, Taiwan;3Department of Internal Medicine, School of Medicine, College of Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, 80708, Taiwan

Agenda PP-31

BASELINE FACTORS ASSOCIATED WITH BETTER RESPONSE TO INSULIN LISPRO LOW MIXTURE OR INSULIN GLARGINE IN DURABLE STUDY 1

THOMAS LEW, 2NAN JIA, 3ANGEL RODRIGUEZ, 4 ZBIGNIEW KINDRACKI 1

Presenting on behalf of Eli Lilly and Company, Indianapolis, USA; 2Eli Lilly and Company, Indianapolis, USA; 3Eli Lilly and Company, Alcobendas, Madrid, Spain; 4Eli Lilly Poland, Warsaw, Poland

PP-32

ASSOCIATION BETWEEN MILD AND SEVERE HYPOGLYCEMIA IN PATIENTS WITH TYPE 2 DIABETES INITIATING INSULIN 1

THOMAS LEW, 2ADREAS FESTA, 2RAN DUAN, 2 HAODA FU 1

Presenting on behalf of Eli Lilly and Company, Indianapolis, USA; 2Eli Lilly and Company, Indianapolis, USA

PP-33

IMPROVEMENT IN HBA1C IN PATIENTS WITH TYPE 2 DIABETES MELLITUS TREATED WITH ONCE-WEEKLY DULAGLUTIDE ACROSS BASELINE BODY MASS INDEX SUBGROUPS AT 26 OR 52 WEEKS 1

THOMAS LEW, 2LUIS ALBERTO VáZQUE, 3 ESTEBAN JóDAR, 4CARLOS TRESCOLI, 5 CLAUDIA NICOLAY, 2JESúS REVIRIEGO, 6 RAFFAELLA GENTILELLA 1

Presenting on behalf of Eli Lilly and Company, Indianapolis, USA; Eli Lilly, Alcobendas, Spain; 3Hospital Universitario Quirón, Madrid, Spain; 4Hospital Universitario de la Ribera, Alzira, Valencia, Spain; 5Lilly Deutschland GmbH, Bad Homburg, Germany; 6Lilly Diabetes, Eli Lilly Italia, Sesto Fiorentino, Italy 2

The

th Annual Meeting of March 19-20, 2016 The Endocrine Society and The Diabetes Association of the R.O.C. (Taiwan)

PP-34

COMPARISON OF EFFICACY AND SAFETY OF TWO STARTING INSULIN REGIMENS IN NONASIAN, ASIAN INDIAN, AND EAST ASIAN PATIENTS WITH TYPE 2 DIABETES: A POST-HOC ANALYSIS OF THE PARADIGM STUDY 1

L JI, 2KW MIN, 3J OLIVIERA, 4T LEW, 5R DUAN

Peking University People’s Hospital, Beijing, China. 2EULJI Hospital, Seoul, Republic of Korea. 3Takeda Pharmaceuticals, San Diego, USA. 4Eli Lilly and Company, Taipei, Taiwan. 5Eli Lilly and Company, Indianapolis, USA.

March 19, 2016 【1st Conference Room】

Luncheon Symposium-1 New Era of Diabetes and Dyslipidemia Management Sponsor: MSD 默沙東

Moderator: Harn-Shen Chen 12:00-13:00

LS-1

Management of Hyperglycemia and Dyslipidemia in Type 2 Diabetes Mellitus: Update on Current Evidence of DPP-4i and Lipid Lowering Combination Therapy CHIH-YUAN WANG Division of Internal Medicine, National Taiwan University Hospital

March 19, 2016 【2nd Conference Room】

Luncheon Symposium-2 SGLT2i - BrandNew Choice for Multi-Aspect T2DM Therapy Sponsor: AstraZeneca 阿斯特捷利康

Agenda Moderator: Yi-Jen Hung 12:00-13:00

LS-2

Apply the Latest Clinical Data of Dapagliflozin to Clinical Practice MING-CHIA HSIEH Division of Endocrinology and Metabolism, Changhua Christian Hospital

March 19, 2016 【3rd Conference Room】

Luncheon Symposium-3 DPP4i Across the CV Continuum Sponsor: Takeda 武田

Moderator: Lee-Ming Chuang 12:00-13:00

LS-3

The Management of Type 2 DM: Considering Cardiovascular Outcomes Studies (EXAMINE & SAVOR & TECOS) of DPP4i CHUNG-SHENG LIN Chung Shan Medical University Hospital

March 19, 2016 【4th Conference Room】

Luncheon Symposium-4 Impact of Diabetes-Specific Nutrition Therapy Sponsor: Abbott 亞培

Moderator: Ching-Ling Lin 12:00-13:00

LS-4

The Clinical and Economic Impact of The Use of Diabetes-Specific Enteral Formula on ICU Patients with Type 2 Diabetes YIN-YI HAN Trauma Department, National Taiwan University Hospital

The

th Annual Meeting of March 19-20, 2016 The Endocrine Society and The Diabetes Association of the R.O.C. (Taiwan)

March 20, 2016 【1st Conference Room】

12:10-12:15

Luncheon Symposium-5 State of The Art T2DM Management: Today and Tomorrow Opening Remark LEE-MING CHUANG

Sponsor: Boehringer Ingelheim/Lilly 百靈佳殷格翰／禮來

Division of Internal Medicine, National Taiwan University Hospital

Moderator: Lee-Ming Chuang 12:15-12:40

Shedding Light on Renal Function: The Emerging Concept of DPP-4i Treatment CHING-LING LIN Division of Endocrinology and Metabolism, Cathay General Hospital

Moderator: Chien-Ning Huang 12:40-13:05

State of The Art T2DM Management: Today and Tomorrow MAX VON EYNATTEN Boehringer Ingelheim company

13:05-13:10

Closing and Panel Discussion CHIEN-NING HUANG Division of Endocrinology and Metabolism, Chung Shan Medical University Hospital

Agenda March 20, 2016 【2nd Conference Room】

Luncheon Symposium-6 Development of Insulin Therapy Optimization Sponsor: Novo Nordisk 諾和諾德

Moderator: Tjin-Shing Jap 12:10-13:10

LS-6

Optimal Insulin Therapy to Type 2 Diabetes Treatment: past, now, and future THOMAS DANNE Department of General Pediatrics, Endocrinology and Diabetes, AUF DER BULT Children’s Hospital

March 20, 2016 【3rd Conference Room】

Luncheon Symposium-7 Clinical Application of GLP-1 RA in Type 2 Diabetes -Focus on Dulaglutide Sponsor: Eli Lilly Company (Taiwan) 台灣禮來

Moderator: Wayne Huey-Herng Sheu 12:10-13:10

LS-7

Clinical Application of GLP-1 RA in Type 2 Diabetes SHIH-TE TU President, Taiwanese Association of Diabetes Educators Division of Endocrinology and Metabolism, Lukang Christian Hospital

The

th Annual Meeting of March 19-20, 2016 The Endocrine Society and The Diabetes Association of the R.O.C. (Taiwan)

March 20, 2016 【4th Conference Room】

Luncheon Symposium-8 T2DM Management: A Thorough Talk on Glucose Variability Sponsor: Novartis 台灣諾華

Moderator: Keh-Sung Tsai 12:10-13:10

LS-8

Glucose Excursions and Diabetes Complications: Focus on Vildagliptin JUN-SING WANG Division of Endocrinology and Metabolism, Taichung Veterans General Hospital

March 20, 2016 【4th Conference Room】

Breakfast Symposium-1 To Accuracy-and Beyond Sponsor: Bayer Diabetes Care 拜耳血糖儀 Opening WAYNE HUEY-HERNG SHEU

08:30-08:40

President, The Diabetes Association of the R.O.C. (Taiwan) Division of Endocrinology and Metabolism, Taichung Veterans General Hospital

Moderator: Shih-Te Tu 08:40-09:10

BS-1

Precision Medicine - Clinical Application of SMBG CHING-LING LIN Division of Endocrinology and Metabolism, Cathay General Hospital

Moderator: Lee-Ming Chuang 09:10-09:20

Discussion

09:20-09:30

Closing Remarks WAYNE HUEY-HERNG SHEU President, The Diabetes Association of the R.O.C. (Taiwan) Division of Endocrinology and Metabolism, Taichung Veterans General Hospital

Agenda March 19,2016(Sat 09:00 -March 20, 2016(Sun)16:00

2016 Award Winners

【The Gallery Outside the 5th Conference Room】

Outstanding Research Award AP-01

IMPROVE GLYCEMIC CONTROL IN PATIENTS WITH TYPE 2 DIABETES HARN-SHEN CHEN Division of Endocrinology and Metabolism, Department of Medicine, Taipei Veterans General Hospital, Taiwan, R.O.C.

Novartis Award AP-02

GENETIC DETERMINANTS OF ANTITHYROID DRUG-INDUCED AGRANULOCYTOSIS BY HUMAN LEUKOCYTE ANTIGEN GENOTYPING AND GENOME-WIDE ASSOCIATION STUDY 1,2,3,4

P-L Chen, 1,5S-R Shih, 6P-W Wang, 7Y-C Lin, 8C-C Chu, 7,9,10 J-H Lin, 1,11S-C Chen, 1,12,13C-C Chang, 1,5,14T-S Huang, 1,15 K S Tsai, 1F-Y Tseng, 1C-Y Wang, 1J-Y Lu, 1W-Y Chiu, 7 C-C Chang, 9Y-H Chen, 7,16Y-T Chen, 7C S-J Fann, 1,3,4,5 W-S Yang & 1,5T-C Chang 1

Division of Endocrinology and Metabolism, Department of Internal Medicine, 2Department of Medical Genetics, National Taiwan University Hospital, 3Graduate Institute of Medical Genomics and Proteomics, 4 Graduate Institute of Clinical Medicine, 5Department of Medicine, College of Medicine, National Taiwan University, 6Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, 7Institute of Biomedical Sciences, Academia Sinica, 8 Immunogenetics Laboratory, Medical Research Department, Mackay Memorial Hospital, 9School of Pharmacy, National Taiwan University, 10 Research Center for Applied Sciences, Academia Sinica, 11Department of Internal Medicine, New Taipei City Hospital, 12Department of Internal Medicine, China Medical University Hospital, 13Department of Internal Medicine, China Medical University, 14Department of Social Medicine, 15 Department of Laboratory Medicine, College of Medicine, National Taiwan University, 16Department of Pediatrics, Duke University Medical Center, Durham, North Carolina 27708, United States of America

The

th Annual Meeting of March 19-20, 2016 The Endocrine Society and The Diabetes Association of the R.O.C. (Taiwan)

AP-03

Glucose Variability and beta- Cell Response by GLP1 Analogue added-on CSII for Patients with Poorly Controlled Type 2 Diabetes 1,2

C-H Lin, 1S-H Hsieh, 1J-H Sun, 3J-S Tsai, 1Y-Y Huang

Division of Endocrinology and Metabolism, Department of Internal Medicine, Chang Gung Memorial Hospital, Linkou, Taiwan; 2Graduate Institute of Clinical Medical Sciences, Chang Gung University, Taoyuan,Taiwan; 3Sun Yat-Sen Cancer Center, Taipei, Taiwan

Merck Sharpe & Dohme Award AP-04

THE ASSOCIATION BETWEEN BODY MASS INDEX AND ALL-CAUSE MORTALITY IN PATIENTS WITH TYPE 2 DIABETES MELLITUS: A 5.5-YEAR PRPPECTIVE ANALYSIS 1

J-F Kuo, 2Y-T Hsieh, 1I-C Mao, 1S-D Lin, 1S-T Tu, 1,3M-C Hsieh

Department of Internal Medicine, Division of Endocrinology and Metabolism, Changhua Christian Hospital, Changhua, Taiwan, R.O.C.; 2 Department of Ophthalmology, National Taiwan University Hospital, Taipei, Taiwan, R.O.C.; 3Graduate Institute of Integrated Medicine, China Medical University, Taichung, Taiwan

AP-05

Genetic Polymorphisms of PCSK2 are Associated with Glucose Homeostasis and Progression to Type 2 Diabetes in a Chinese Population. 1

TJ Chang, 2YF Chiu, 3WH Sheu, 4KC Shih, 5,6CM Hwu, 7 Quertermous T, 8YS Jou, 1SS Kuo , 1,9 YC Chang, 1,10 LM Chuang 1

Department of Internal Medicine, National Taiwan University Hospital, Taipei 10002, Taiwan; 2Department of Bioinformatics and Biostatistics, National Health Research Institutes, Zhunan Town, Miaoli County 35053, Taiwan; 3 Department of Internal Medicine, Taichung Veterans General Hospital, Taichung 40705, Taiwan; 4Division of Endocrinology and Metabolism, Taipei Veterans General Hospital, Taipei 11217, Taiwan; 5Section of General Medicine, Department of Medicine, Taipei Veterans General Hospital, Taipei 11127, Taiwan; 6Faculty of Medicine, National Yang-Ming University School of Medicine, Taipei 11221, Taiwan; 7Division of Cardiovascular Medicine, Falk Cardiovascular Research Building, Stanford University School of Medicine, Stanford, CA 94305, USA; 8Institute of Biomedical Sciences, Academia Sinica, Taipei 11529, Taiwan; 9Graduate Institute of Medical Genomics and Proteomics, National Taiwan University College of Medicine, Taipei 10055 Taiwan; 10Institute of Epidemiology and Preventive Medicine, College of Public Health, National Taiwan University, Taipei 10055, Taiwan.

Agenda

Novo Nordisk Award AP-06

CLINICAL CHARACTERISTICS AND RISK FACTOR ANALYSIS FOR LOWER-EXTREMITY AMPUTATIONS IN DIABETIC PATIENTS WITH FOOT ULCER COMPLICATED BY NECROTIZ FASCIITIS 1

I-Wen Chen, 1Hui-Mei Yang, 2Cheng-Hsun Chiu, 3 Jiun-Ting Yeh, 1Chung-Huei Huang, 1Yu-Yao Huang 1

Division of Endocrinology and Metabolism, Department of Internal Medicine, Chang Gung Memorial Hospital, Chang Gung University, Taiwan; 2 Molecular Infectious Disease Research Center, Division of Pediatric Infectious Diseases, Department of Pediatrics, Chang Gung Memorial Hospital, Chang Gung University, Taiwan; 3Division of Trauma Plastic Surgery, Department of Plastic and Reconstructive Surgery, Chang Gung Memorial Hospital, Chang Gung University, Taiwan.

The

th Annual Meeting of March 19-20, 2016 The Endocrine Society and The Diabetes Association of the R.O.C. (Taiwan)

Prof. André Lacroix, M.D. Personal Information Nationality: Canadian Professor, Department of Medicine, Division of Endocrinology CHUM Director, Laboratory of endocrine pathophysiology, CRCHUM Tour Viger, 900, rue Saint-Denis, Rm R08-474, Montréal (Québec) H2X 0A9 E-mail: andre.lacroix@umontreal.ca Pr. Lacroix completed M.D. degree in 1972 and specialization in endocrinology in 1977 at Université de Montréal. This was followed by Endocrine fellowship at Vanderbilt University in Nashville, TN from 1976-78 with Grant W Liddle, David N Orth, TJ McKenna, and at the National Institutes of Health in Bethesda, MD from 1978-80 with Marc E Lippman and during a sabbatical year of biotechnology in 1986 with MB Sporn and Anita Roberts. Since 1980, he has been Director of Endocrine Pathophysiology laboratory at Institut de Recherches Cliniques de Montréal (IRCM) until 1992 and now at the CHUM Research center (CRCHUM). He served as chief of Endocrine Division at Hôtel-Dieu hospital and as Director of the Endocrinology Training Program of Université de Montréal. He was Chairman of the Department of Medicine from 2002-2008 and Associate Director General for Medical and Academic Affairs at CHUM (2008-2012). He served as president of the Canadian Society of Endocrinology and Metabolism (2005-2007) and on the executive board of the International Society of Endocrinology (2010-16). He is currently co-editor of the Adrenal Section of UpToDate (Boston, MA), Senior Editor of the European Journal of Endocrinology, editorial board member of Journal of Clinical Endocrinology and Metabolism. He received the Medical Leadership award from CHUM Foundation in 1999 and the Robert Volpé 2010 award from CSEM in recognition for his contributions to Endocrinology in Canada. He was elected Fellow of the Canadian Academy of Health Sciences in 2008 (FCAHS). Major Areas of Research: Genetics and pathophysiology of adrenal tumors and hyperplasias leading to Cushing’s syndrome, primary aldosteronism and adrenal tumorigenesis. Role of aberrant adrenal hormone receptors in adrenal overfunction. New drugs in the therapy of Cushing’s disease and primary aldosteronism, of adrenocortical cancer and pheochromocytomas. He has published more than 180 articles or book chapters, 250 scientific meeting abstracts and was invited to give 250 conferences at national and international institutions or scientific meetings. Selected publications 1. Lacroix, A., Bolté, E., Tremblay, J., Dupré, J., Poitras, P., Fournier, H., Garon, J., Garrel, D., Bayard, F., Taillefer, R., Flanagan, R., and Hamet, P. Gastric inhibitory polypeptide-dependent cortisol hypersecretion - a new cause of Cushing’s syndrome. N. Engl. J. Med.; 327:974-980. 1992 (274citations) IF 47.05 2. Gagner, M., Lacroix, A., and Bolté, E. Laparoscopic approach to adrenalectomy in Cushing’s syndrome and pheochromocytoma. Letter to the Editor. N. Engl. J. Med.; 327:1033. 1992 (1361 citations) IF 47.05 38

CV & Abstract 3. Lacroix, A., N’Diaye, N., Tremblay, J., and Hamet, P. Ectopic and abnormal hormone receptors in adrenal Cushing’s syndrome. Endocrine Reviews, 22 :75-110, 2001 (278 citations). IF 19.76 4. Lacroix, A., Tremblay, J., Rousseau, G., Bouvier, M., and Hamet, P. Propranolol therapy for ectopic b‑adrenergic receptors in adrenal Cushing’s syndrome. New Engl. J. Med.; 337:1429-1434. 1997 (178 citations) IF 47.05 5. Lacroix, A., Hamet, P., Boutin, JM. Leuprolide acetate therapy in Luteinizing Hormone-dependent Cushing’s syndrome. New England Journal of Medicine. 341:1577-81. 1999 (169 citations). IF 47.05 6. Arnaldi, G., Angeli, A., Atkinson, A.B., Bertagna, X., Cavagnini, F., Chrousos, G., Fava, G.A., Findling, J., Gaillard, R.C., Grossman, A.B., Kola, B., Lacroix, A., Mancini, T., Mantero F., Newell-Price, J., Nieman, L.K., Sonino, N., Vance M.L., Giustina A., Boscaro M. Diagnosis and complications of Cushing’s syndrome : A consensus statement. J. Clin. Endocrinol. Metab., 88(12):5593-602, 2003. (927 citations) IF 6.20 7. Biller B.M.K., Grossman A.B., Stewart P.M., Melmed S., Bertagna X., Bertherat J., Buchfelder M., Colao A., Hermus A.R., Hofland L.J., Klibanski A., Lacroix A., Lindsay J.R., Newell-Price J., Nieman L.K., Petersenn S., Sonino N., Stalla G.K., Swearingen B., Vance M.L., Wass J.A.H. and Boscaro M. Treatment of ACTH-dependent Cushing’s Syndrome: A Consensus Statement. J. Clin. Endocrinol. Metab. 93: 2454-62, 2008 (452 citations) 8. Lampron A, Bourdeau I, Oble S, Godbout A, Schurch W, Arjane P, Hamet P, and Lacroix A. Regulation of aldosterone secretion by several aberrant receptors including for GIP in a patient with an aldosteronoma. J Clin Endocrinol Metab. 94:750-6, 2009. (27 citations) IF 6.20 9. Hsiao H-P, Verma S, Nandagopal R, Boikos SA, Bourdeau I, Keil MF, Robinson-White AJ, Kirschner LS, Lacroix A, and Stratakis CA. A Molecular and Clinical Genetic Investigation of ACTH-Independent Macronodular Adrenal Hyperplasia Compared to Other, Common Adrenocortical Tumors: Evidence for Heterogeneity, Overlap with Other Tumor Syndromes and Frequent But Atypical Hormonal Secretion. J Clin Endo Metab 94: 2930-37, 2009. (53 citations) IF 6.20 10. Lacroix A. Approach to the patient with adrenal carcinoma. J Clin Endocrinol Metab. 95:4812-22, 2010. (52 citations) IF 6.20 11. Lacroix A, Bourdeau I, Lampron A, Mazzuco TL, Tremblay J, Hamet P. Aberrant G-protein coupled receptor expression in relation to adrenocortical overfunction. Clin Endocrinol (Oxf).73:1-15, 2010 (47 citations) IF 3.32 12. Godbout A, Manavela M, Danilowicz K, Beauregard H, Bruno OD, Lacroix A. Cabergoline monotherapy in the long-term treatment of Cushing’s disease. Eur J Endocrinol. 163: 1-9, 2010 (83 citations) IF 3.48 13. Colao AM, Petersenn S, Newell-Price J, Findling JW, Gu F, Maldonado M, Schoenherr U, Mills D, Salgado LR, and Biller BMK, on behalf of the Pasireotide B2305 Study Group (Lacroix A). A 12-Month Phase 3 Study of Pasireotide in Cushing’s Disease. N Engl J Med 366 : 914-24, 2012. IF 47.05 14. Fassnacht M, Terzolo M, Allolio B, Baudin E, Haak H, Berruti A, Welin S, Schade-Brittinger C, Lacroix A Jarzab B, Sorbye H, Torpy D, Stepan V, Arlt W, Schteingart D, Kroiss M, Leboulleux S, Sperone P, Sundin A, Hermsen I, Hahner S, Willenberg HS, Tabarin A, Quinkler M, de la Fouchardière C, Schlumberger M, Mantero F, Weismann D, Beuschlein F, Gelderblom H, Wilmink H, Sender M, Edgerly M, Kenn W, Fojo T, Mueller HH, Skogseid B, for the FIRM-ACT study group. Combination Chemotherapy in Advanced Adrenocortical Carcinoma. N Engl J Med 39

The

th Annual Meeting of March 19-20, 2016 The Endocrine Society and The Diabetes Association of the R.O.C. (Taiwan)

366(23):2189-97, 2012 May 2. (155 citations) IF 47.05 15. Lacroix A. Heredity and cortisol regulation in bilateral macronodular adrenal hyperplaisia. Editorial N Engl J Med. 369 Nov 28:2147-2149, 2013(8 citations) IF 47.05 16. Alencar, G.A., Lerario, A.M., Nishi, M.Y., Mariani, B.M.M., Almeida, M.Q., Tremblay, J., Hamet, P., Bourdeau, I., Zerbini, M.C.N., Pereira, M.A.A., Gomes, G.C., Rocha, M.D.S., Chambo, J.L., Lacroix, A., Mendonca, B.B., Fragoso, M.C.B.V. ARMC5 Mutations are a frequent cause of primary macronodular adrenal hyperplasia. J. Clin. Endocrinol. Metab. 99: E1501-1509, 2014. (12 citations) IF : 6.20 17. De Venanzi, A., Alencar, G.A., Bourdeau, I., Fragoso, M.C.B.V., and Lacroix, A. Primary bilateral macronodular adrenal hyperplasia. Curr. Opin. Endocrinol. Diabetes Obes. 21: 177-184, 2014 (doi: 10.1097/MED). 18. Bourdeau, I., Oble, S., Magne, S., Lévesque, I. Caceres, K., Nolet, S., Awadalla, P., Tremblay, J., Hamet, P., Fragoso, M.C.B.V., Lacroix, A. ARMC5 mutations in a large French-Canadian family with cortisol-secreting B-adrenergic/vasopressin responsive bilateral macronodular adrenal hyperplasia. Eur. J. Endocrinol. 174: 85–96, 2016 19. El Ghorayeb, N., Bourdeau, I., Lacroix, A. Multiple aberrant hormone receptors in Cushing’s syndrome. Eur J Endocrinol. Eur J Endocrinol. 2015 Oct;173(4):M45-60. doi: 10.1530/EJE-150200. Epub 2015 May 13. Review 20. Lacroix A, Felders RA, Stratakis CA, Nieman L. Cushing’s syndrome. Invited Seminars. Lancet. 2015 Aug 29; 386(9996):913-27. doi: 10.1016/S0140-6736(14)61375-1. Epub 2015 May 21. Review

CV & Abstract PL

New Developments in Cushing's Syndrome ANDRÉ LACROIX Professor of Medicine, Division of Endocrinology, Centre hospitalier de l’Université de Montréal (CHUM).

Chronic exposure to excess glucorticoids results in the diverse manifestations of Cushing’s syndrome, including debilitating morbidities and increased mortality. Recent progress revealed genetic and molecular mechanisms responsible for excess cortisol secretion by primary adrenal lesions and of ACTH from corticotroph tumors. These include USP8 mutations in corticotroph tumors, PRKACA mutations in cortisol secreting adenomas, ARMC5 mutations and aberrant receptor regulated paracrine production of ACTH in bilateral macronodular adrenal hyperplasia. New biochemical and imaging diagnostic approaches and progress in surgical and radiotherapy techniques have improved the management of patients. The therapeutic goal is to normalize tissue exposure to cortisol in order to reverse the increased morbidity and mortality. Optimal treatment is selective and complete resection of the causative tumor, allowing eventual normalization of the hypothalamic-pituitary-adrenal axis, maintenance of pituitary function and avoidance of tumor recurrence. The development of new targeted drugs interfering with the molecular causes should offer clinicians several choices to better treat patients with residual cortisol excess. However, the long-term effects and co-morbidities associated with hypercortisolism require ongoing care of patients affected by this challenging syndrome.

The

th Annual Meeting of March 19-20, 2016 The Endocrine Society and The Diabetes Association of the R.O.C. (Taiwan)

DT-1

Prof. Chin-Hsiao Tseng, M.D., Ph.D. Personal Information Nationality: Taiwan Position: Professor Department: Department of Internal Medicine Organization: National Taiwan University College of Medicine Email: ccktsh@ms6.hinet.net Educational background & professional experience (in sequence of the latest year) 2009.8- Department of Internal Medicine, National Taiwan University College Professor of Medicine 1993-1996 School of Public Health, National Taiwan University PhD 1979-1986 School of Medicine, National Taiwan University College of Medicine MD Research Interests 1. Diabetes epidemiology 2. Cancer risk related to antidiabetic drugs 3. Arsenic and diabetes Publications (5 important publications – latest sequence) 1. Tseng CH. Use of metformin and risk of kidney cancer in patients with type 2 diabetes. Eur J Cancer. 2016;52:19-25. 2. Tseng CH. Sitagliptin and pancreatic cancer risk in patients with type 2 diabetes. Eur J Clin Invest. 2016;46:70-79. 3. Tseng CH. Sitagliptin increases acute pancreatitis risk within 2 years of its initiation: A retrospective cohort analysis of the National Health Insurance database in Taiwan. Ann Med. 2015;47:561-9. 4. Tseng CH, Lee KY, Tseng FH. An updated review on cancer risk associated with incretin mimetics and enhancers. J Environ Sci Health C Environ Carcinog Ecotoxicol Rev. 2015;33:67-124. 5. Tseng CH. Obesity paradox: differential effects on cancer and noncancer mortality in patients with type 2 diabetes mellitus. Atherosclerosis. 2013;226:186-192.

CV & Abstract DT-1

IDF Diabetes Atlas 2015 and the Trends of Diabetes and its Complications in Taiwan

從 IDF Diabetes Atlas 2015 看臺灣糖尿病盛行率與併發症之趨勢 CHIN-HSIAO TSENG 曾慶孝 Department Internal Medicine, National Taiwan University College of Medicine, Taipei, Taiwan, ROC 臺大醫學院醫學系內科

Diabetes is a common non-communicable disease that affects hundreds of millions of people worldwide. In the year 2015, the International Diabetes Federation estimated a total global number of 415 million people suffering from diabetes, with 1 in 11 adults having diabetes. Nearly half of the people with diabetes do not know that they are having diabetes. What is worse is that approximately 5.0 million people died of diabetes in 2015, and nearly half of them (46.6%) were under the age of 60. The incidence and prevalence of diabetes is on the rise and the global prevalence of diabetes for adults (20-79 years) was estimated to rise from 8.8% in 2015 to 10.4% in 2040. In Taiwan, a series of epidemiological screening programs have been conducted during the past five decades. In Taipei city, the prevalence of diabetes for residents aged 40 years or older has been increasing from 5.1% in 1970, to 7.1% in 1979 and to 8.2% in 1986. During 1993-1996 and 20052008, respectively, two cycles of the Nutrition and Health Survey in Taiwan (NAHSIT) based on similar sampling strategy were conducted among residents aged 19 years or older. The crude nation-wide prevalence of diabetes for residents aged 19 years or older increased from 5.33% (age-standardized rates: 6.21%) in the first NAHSIT survey to 9.05% (age-standardized rates: 7.80%) in the second NAHSIT survey. The increased prevalence of diabetes was especially striking for the older population aged 65 years or older, from 17.13% to 25.73%, for the first and second survey, respectively. Another national survey, the Taiwanese Survey on Hypertension, Hyperglycemia and Hyperlipidemia, was conducted in 2002, and from a random sample of 4683 residents aged 25-74 years, the crude prevalence of diabetes in men (9.1%) was significantly higher than that in women (5.6%). By continuously following a large nationally representative cohort of patients with diabetes recruited since 1995 in Taiwan, approximately 70% of the diabetic death would not be ascribed to diabetes on death certificates in Taiwan. The diabetic men have higher risk of dying than women and diabetic patients have excess mortality while compared to the general population. A recent followup of the cohort for up to 17 years showed that 10.9% died under the age of 60. Age, insulin use and smoking significantly predicted cancer and non-cancer death; and hypertension, fasting glucose and dyslipidemia showed differential impacts on cancer and non-cancer death, and were significantly predictive for non-cancer death. Screen-detected diabetes and a higher body mass index provide a survival advantage, especially for non-cancer death. 43

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th Annual Meeting of March 19-20, 2016 The Endocrine Society and The Diabetes Association of the R.O.C. (Taiwan)

DT-2

Shu-Ti Chiou, M.D., Ph.D. Personal Information Nationality: Taiwan Position: Director-General Organization: Health Promotion Administration, Ministry of Health & Welfare, Taiwan Email: stchiou@hpa.gov.tw Educational background & professional experience (in sequence of the latest year) 2014~Present School of Medicine, National Yang-Ming Adjunct Associate University, Taiwan Professor 2013~Present Health Promotion Administration, Ministry of Director-General Health and Welfare, Taiwan 2013~2014 School of Medicine, National Yang-Ming Adjunct Assistant University, Taiwan Professor 2013~Present The International Union for Health Promotion Global Vice President and Education (IUHPE) for Partnerships 2012~2014 International Network of Health Promoting Chair of Governance Hospitals and Health Services (initiated by WHO) Board 2010~2012 International Network of Health Promoting Vice Chair of Hospitals and Health Services (initiated by WHO) Governance Board 2009~2013 Bureau of Health Promotion, Department of Director-General Health, Taiwan Research Interests 1. Health Policy 2. Quality of Medical Care Research Publications (5 important publications – latest sequence) 1. Lee CC, Chiou ST, Chen LC, Chien LY. Breastfeeding-Friendly Environmental Factors and Continuing Breastfeeding Until 6 Months Postpartum: 2008–2011 National Surveys in Taiwan. Birth. 2015;42(3):242-8. 2. Chiou ST, Chen LC, Yeh H, Wu SR, Chien LY. Early Skin-to-skin Contact, Rooming-in, and Breastfeeding: A Comparison of the 2004 and 2011 National Surveys in Taiwan. Birth. 2014; 41:3338. 3. Chiou ST, Wu CY, Hurng BS, Lu TH. Changes in the Magnitude of Social Inequality in the Uptake of Cervical Cancer Screening in Taiwan, a Country Implementing a Population-based Organized Screening Program. International Journal for Equity in Health. 2014; 13: 4. 4. Chiou ST, Lu TH. Changes in Geographic Variation in the Uptake of Cervical Cancer Screening in Taiwan: Possible Effect of “Leadership Style Factor＂? Health Policy. 2014; 114: 64-70. 5. Chiou ST, Chen LK. Towards age-friendly hospitals and health services. Archives of Gerontology and Geriatrics. 2009; 49 Suppl 2: S3-6. 44

CV & Abstract DT-2

臺灣糖尿病之現況及展望 SHU-TI CHIOU 邱淑媞 Director-General, Health Promotion Administration, Ministry of Health and Welfare 衛生福利部國民健康署

全世界目前有 3 億 8,200 萬罹患糖尿病，如果這些人組成一個國家，那麼在國家人口來排名上，「糖尿病國」的人口僅次於中國大陸及印度，位居世界第三 ! 所以糖尿病是一個嚴重威脅世界健康之慢性病。在台灣，糖尿病是國人十大死因第 5 位，民國 103 年因糖尿病死亡的人數達 9,845 人。依據 102-103 年「國民營養健康狀況變遷調查」發現，18 歲以上國人糖尿病盛行率為 12.4%，全國約近有 150 萬名糖尿病友，且每年以 25,000 名的速度持續增加，糖尿病及其所引發的併發症影響國人健康不容小覷。糖尿病照護最重要的是增進病患自我照護能力，延緩糖尿病併發症之發生，政府為了提升照護品質，辦理糖尿病共同照護網，宜蘭縣衛生局首當其衝在民國 85 年率其他縣市之先，全面推動糖尿病共同照護，迄民國 92 年已推廣至全國 22 縣市，透過公共衛生部門、臨床醫療團隊、專業組織、病友團體等的結合，強化縣市糖尿病防治工作。為落實糖尿病照護醫事人員能遵行一致性的品質標準來照護病人，政府建立了醫事人員訓練及認證制度，迄今已完成 9,026 人認證。健康保險署亦以糖尿病共同照護網為基礎，加上論質計酬設計，推動「糖尿病醫療品質支付服務方案」，透過醫療院所對病人的追蹤管理，協助病患規律就醫與自我健康管理。國民健康署與縣市衛生局以質量並濟方式全力推動，希望所有糖尿病病人都能獲得專業照護，訂定照護涵蓋率、糖尿病人尿液微量白蛋白檢查率，及眼底檢查率等工作重點有系統的提昇服務品質，截至 103 年照護率已達 40.4%，但仍須經各界齊心努力，讓所有病人都能獲得優質照護。為了更有效提升照護率，國民健康署透過不同平台，國民健康從五大面向分進合擊：1. 跨單位合作：如跨部會合作、縣市衛生單位協力、健康促進醫院計畫、高齡友善醫院計畫等，加強橫向連結強化彼此合作。2. 指標管理：定期將醫療院所加入方案效益及各院所各項指標表現回饋予各院所，以形成良性競爭互相學習氣氛，激勵院所向上提升照護品質。3. 增能縣市：辦理縣市推動經驗分享會，強化縣市衛生單位糖尿病防治規劃與推動能力。4. 提升誘因：補助部分經費給機構以推廣糖尿病健康促進機構，並舉辦「績優糖尿病健康促進機構表揚暨新加入機構授證典禮」對優良院所酌予獎勵。5. 強化病友團體：為增進病人權能，於全國成立 514 個糖尿病友團體，分佈於 360 個鄉鎮市區，達全國鄉鎮市區涵蓋率近 97.8%，強化糖尿病高危險群及糖尿病人「控糖」之自我健康管理能力等。在各界努力下，過去十年中，台灣糖尿病標準化死亡率已由 91 年之 30/ 每十萬人口下降至 103 年的 26/ 每十萬，降幅達 13%。惟，因應全球肥胖及人口老化浪潮，仍須於健保給付機制上強化對品質之監測與獎勵，使品質成為一種習慣，使健康成為醫、病、健保、與社會多贏的支點。

The

th Annual Meeting of March 19-20, 2016 The Endocrine Society and The Diabetes Association of the R.O.C. (Taiwan)

DT-3

I-Chieh Mao, M.D. Personal Information Nationality: Taiwan Position: Chief Department: Endocrinology and Metabolism Organization: Lukang Christian Hospital Email: 143814@cch.org.tw

Educational background & professional experience (in sequence of the latest year)

1998-2005

China Medical University

2007-2013

Changhua Christian Hospital

2013-

Lukang Christian Hospital

CV & Abstract DT-3

The Current and Future Prospects of Continuous Glucose Monitoring System (CGMS) in Diabetes Care

連續血糖監測系統的現在與未來展望 I-CHIEH MAO 毛羿傑 Department of Endocrinology and Metabolism, Lukang Christian Hospital, Changhua County, Taiwan, ROC 鹿港基督教醫院內分泌新陳代謝科

Continuous glucose monitoring system (CGMS) technology has shown its potential in improving the he lives of people with type 1 diabetes. Because the real-time feedback it provides about therapeutic interventions and variations in lifestyle or dietary intake, CGMS has made the attainment of near-normal blood glucose concentrations an achievable goal for most patients with diabetes and reduces diabetic complications as well. Several challenges remain to be solved, including the accuracy of the readings,accessibility in wearing the devices, high economic burden, limited approved clinical use and absence of National Health Insurance reimbursement for the technology. In the near future, CGMS undoubtedly will show its power in diabetes care. In Lukang Christian Hospital, we have established a standard algorithm for CGMS interpretation. In the near future, customized service, smartphone connectivity, patients management app, weight control in pre-DM or obese population will highlight the revolution of CGMS and would be integrated into daily clinical practice.

The

th Annual Meeting of March 19-20, 2016 The Endocrine Society and The Diabetes Association of the R.O.C. (Taiwan)

DT-4

Prof. Chih-Cheng Hsu, M.D., Ph.D. Personal Information Nationality: Taiwan Position: Deputy Director Department: Institute of Population Health Sciences Organization: National Health Research Institutes Email: cch@nhri.org.tw Educational background & professional experience (in sequence of the latest year) 2014 Institute of Population Health Sciences/ Deputy Director National Health Research Institutes 2000 Tulane School of Public Health DrPH 1986 National Yang Ming Medical College MD Research Interests 1. Epidemiology of Diabetes Mellitus 2. Epidemiology of Chronic Kidney Disease 3. Geriatric syndrome Publications (5 important publications – latest sequence) 1. Hsu CC, Almulaifi A, Chen JC, Ser KH, Chen SC, Hsu KC, Lee YC, Lee WJ. Effect of Bariatric Surgery

vs Medical Treatment on Type 2 Diabetes in Patients With Body Mass Index Lower Than 35: Five-Year Outcomes. JAMA Surg. 2015 Dec 1;150(12):1117-24. 2. Hung SC, Chang YK, Liu JS, Kuo KL, Chen YH, Hsu CC*, Tarng DC. Metformin use and mortality in patients with advanced chronic kidney disease: a national retrospective observational cohort study. Lancet Diabetes Endocrinol. 2015 Aug;3(8):605-14. 3. Hsu CC*, Tai TY. Long-term glycemic control by a diabetes case-management program and the challenges of diabetes care in Taiwan. Diabetes Res Clin Pract. 2014 Dec;106 (Suppl 2):S328-332. H 4. su CC, Chang HY, Huang MC, Hwang SJ, Yang YC, Lee YS, Shin SJ, Tai TY. HbA1c variability is associated with microalbuminuria development in type 2 diabetes: a 7-year prospective cohort study. Diabetologia. 2012 Dec;55(12):3163-3172. 5. Hsu CC, Lee CH, Wahlqvist ML, Huang HL, Chang HY, Chen L, Shih SF, Shin SJ, Tsai WC, Chen T, Huang CT, Cheng JS. Poverty increases type 2 diabetes incidence and inequality of care despite universal health coverage. Diabetes Care. 2012; 35:2286–2292.

CV & Abstract DT-4

Trend and Factors Associated with Healthcare Use and Costs in Type 2 Diabetes Mellitus: A Decade Experience of a Universal Health Insurance Program

從臺灣糖尿病治療、衛教現況看未來 CHIH-CHENG HSU 許志成 Institute of Population Health Science, National Health Research Institutes, Zhunan, Taiwan 國家衛生研究院群體健康科學研究所

Little is known about how a universal national health insurance (NHI) program with costcontainment strategies affect costs and quality of diabetes care. To examine the trends of healthcare use and costs for patients with type 2 diabetes mellitus (T2DM) in Taiwan over the last decade, and to identify factors associated with high healthcare cost and poor diabetes care, this talk will delineate the pattern of healthcare use and costs for T2DM in 2000-2010. We used representative adult T2DM patients and age- and gender-matched non-diabetes individuals selected from the 2000, 2005, and 2010 NHI Research Databases to conduct this study. Healthcare use included physician visits, hospital admissions, and antidiabetic drug prescriptions. Indicators of diabetes management included completeness of recommended diabetes tests and medication adherence, assessed using medication possession ratio. Generalized linear and logistic regression models were used to identify factors associated with medical costs and diabetes care. The results of this study show the total healthcare cost per diabetes patient was approximately 2.8-fold higher than that for non-diabetes individual. The growth of healthcare cost per diabetes patient was significantly contained by about 3,694 NTD (3.6%) between 2005 and 2010, but diabetes care improved over the decade. Diabetes duration, income, place of residence, continuity of care, and enrollment to a pay-for-performance (P4P) program were associated with healthcare costs and diabetes management. The effects of P4P program and some public health measures implemented to support diabetes care were also discussed. This talk will conclude that healthcare costs can be controlled without sacrificing the quality of diabetes care by implementing P4P programs and effective health policies favorable for diabetes care.

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Prof. Leilani B. Mercado-Asis, M.D., Ph.D. Personal Information Nationality: Filipino Position: Professor Department: Internal Medicine Organization: University of Santo Tomas Hospital Email: lanibmasis@gmail.com Educational background & professional experience (in sequence of the latest year) EDUCATIONAL BACKGROUND 2013-2016 Completed graduate Certification on Distance Education/ University of the Philippines 2009-2012 Masteral in Public Health Major in Biostatistics University of the Philippines PROFESSIONAL EXPERIENCE Present Department of Medicine, Hospital of the Infant Jesus October 2012Department of Medical Education and Research October 2013 UST Hospital June 2010Department of Medicine May 2012 UST Faculty of Medicine and Surgery July 2001Section of Endocrinology, Diabetes and July 2010 Metabolism, Department of Medicine UST Hospital Oct 2002 Philippine Orthopedic Hospital Sept 2003

Chairman Research Coordinator Chairman Chief Medical Specialist I

Research Interests 1. PITUITARY 2. ADRENAL 3. DIABETES MELLITUS TYPE2 Publications (5 important publications – latest sequence) 1. Acromegaly with cardiomyopathy,cardiac thrombus and hemorrhagic cerebral infract: A case report of therapeutic dilemma with review of literature. Int J Endocrinol 13(2). (April 2015) 2. Successful Reduction in the size of cystic thyroid nodules with 131iodine therapy Journal of Endocrinology and Metabolism;4:3:12-18 (2014) 3. Removal of dominant adrenal lateralized by glucagon-stimulated adrenal venous sampling alleviates hypertension in bilateral pheochromocytoma. Journal of Life Sciences, ISSN 1934-7391, USA 7:6. (June 2013) 4. Pheochromocytoma: Unmasking the Chameleon.in: Koch CA, Chrousos GP (eds.). Contemporary Endocrinology. Endocrine Hypertension. Springer, New York 2013, pp123-148. (2013) 5. Postprandial peaking and plateauting of trglyceride and VLDL were observed in patients with cardiovascular disease maintained on low fat diet and statin treatment. International Journal of Endocrinology and Metabolism, 10(4):75-81. (2012) 50

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The NIH-UST- ASIAN Collaboration LEILANI B. MERCADO-ASIS Internal Medicine, University of Santo Tomas Hospital, Manila, Philippines

In 2008, the University of Santo Tomas Section of Endocrinology and Metabolism and the National Institutes of Health USA entered into a teaching collaboration, so-called UST-NIH Fellowship Training Program under the tutelage of Dr, Karel Pacak. To date, over 20 fellows have rotated to the NIH for 6 months after a 2-year training at UST Hospital. Dr. Pacak developed a program where the Philippine trainees are able to engage in patient care, diagnosis and management, Likewise, research endeavor and opportunities flourished yielding excellent protocol development and journal and book chapter publications. The NIH scientific collaboration also opened the door to the establishment of Asian Alliance for the Study of Neuroendocrine Tumors (AASNT). This is an organization composed of endocrinologists in the ASEAN countries interested in the aforementioned diseases. Several AASNT symposia have been carried out; such as in the Philippines, Vietnam and Malaysia. Foremost and noblest of the collaboration is the established referral system between NIH, Philippines (UST), and the ASEAN countries on patient diagnosis and management.

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Major General Yupin Benjasuratwong, M.D. Personal Information Nationality: Thai Position Consultant and Lecturer at Division of Endocrinology Department: Department of Medicine Organization: Phramongkutklao College of Medicine Email: benjasuratwong@yahoo.com Educational background & professional experience (in sequence of the latest year) 1994 The Endocrine Society of Thailand /The Diploma of the Thai Subspecialty Board Royal College of Physicians of Thailand of Endocrinology and Metabolism 1990 Thyroid Study Unit, University of Chicago, USA Certificate in Research Fellowship Thai Board of Internal Medicine 1982 Faculty of Mdicine , Siriraj Hospital, Mahidol University/ The Royal College of Physicians of Thailand Research Interests 1. Diabetes 2. Thyroid 3. Pituitary Publications (5 important publications – latest sequence) 1. Petch Rawdaree, Chaicharn Deerochanawong, Thavatchai Peerapatdit, Nuntakorn Thongtang,Sompongse Suwanwalaikorn, Ampai Khemkha, Yupin Benjasuratwong, Apussanee Boonyavarakul, et al. Efficacy and safety of generic and original pioglitazone in type 2 diabetes mellitus : A multicenter, a doubleblinded, randomized-controlled study. J Med Assoc Thai 2010; 93 (11):1249-55. 2. Rawdaree P, Ngarmukos C, Deerochanawong C, Suwanwalaikorn S, Chetthakul T, Krittiyawong S, Benjasuratwong Y, Bunnag P , Kosachunhanun N, Plengvidhya N, Reelawattana R, Prathipanawatr T, Likitmaskul S, Mongkolsomlit S. Thailand Diabetes Registry (TDR) Project: Clinical Status and Long Term Vascular Complications in Diabetic Patients. J Med Assoc Thai 2006;89(Suppl 1): S1-9. 3. Kosachunhanun N, Benjasuratwong Y, Mongkolsomlit S, Rawdaree P, Plengvidhya N, Reelawattana R, Bunnag P, Prathipanawatr T, Krittiyawong S, Suwanwalaikorn S, Deerochanawong C, Chetthakul T,Ngarmukos C,Komoltri C. Thailand Diabetes Registry (TDR) Project: Glycemic Control in Thai Type 2 Diabetes.and Its Relation to Hypoglycemic Agent Usage. J Med Assoc Thai 2006;89(Suppl 1): S66-71. 4. Ruengkanchanasetr P, Bangchuad T,Sithinamsuvan P, Benjasuratwong Y, Chuankrerkkul W, Ubolvatra S, and Supaporn T. Hypothalamic neurocysticercosis presents with polyuria: a first report of an unusual manifestation. Nephrol Dial Transplant 2005. 5. Puavili G, Kheesukapan P, Chanprasertyotin S, Chandraprasert S, Suwanvilaikorn S, Nitiyanant W, Deerochanawong C, Benjasuratwong Y, Munskul N, Pongchaiyaikul C, Kespechara K, Montreewasuwat N. Random capillary plasma glucose measurement in the screenig of diabetes mellitus in high risk subjects in Thailand. Diabetes Res. Clin Prac 2001;51:125-131. 52

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The Present and Future of Endocrinology in Thailand YUPIN BENJASURATWONG First Vice President, The Endocrine Society of Thailand Division of Endocrinology and Metabolism, Department of Medicine , Phramongkutklao College of Medicine, Bangkok , Thailand.

The Endocrine Society of Thailand (EST) was established in 1981 in connection with the organization of the ASEAN Federation of Endocrine Societies (AFES). Currently, there are 632 members including 556 physicians, 22 scientists, 15pharmacists, 18 nurses and 10 dietitians. The formal fellowship training in Endocrinology and Metabolism was started in 1993 with 6 training centers for 11 trainee positions per year. It has grown now to 9 training centers with 19 positions per year. Currently, there are 254 physicians with Diploma of the Thai Subspecialty Board of Endocrinology and Metabolism. However, most of the certified endocrinologists practice in Bangkok. Each training center has to fulfill prerequisite requirements including the numbers of certified staffs, numbers of patients with endocrine diseases (out-patient and in-patient), capability for hormone assays as well as dynamic endocrine function tests, imaging study, and fine needle aspiration (FNA) of thyroid. Reaccreditation of training centers is performed every 5 years. A core curriculum, training activities and examination process have been approved by the Royal College Physicians of Thailand (RCPT) and medical council. The EST provide regular educational activities for members, trainees and other healthcare providers such as interhospital endocrine conference, basic endocrinological science and clinical practice courses. The most important event is the EST annual meeting where most of our members gather together, exchange and update information on endocrine disease and EST activities. Also, joint meeting with other medical specialties are encouraged to foster more interdisciplinary collaboration. The EST has close relationship with the Diabetes Association of Thailand (DAT) The two organizations have worked together to update the country’s diabetes guideline every 3 years. Joint cooperation on Type 1 diabetes registry project is in the planning process. One of the missions of EST is to help promote research related to endocrinology in Thailand. Each year the EST gives away two research grants as well as travel grants for young endocrinologists to present their research at international meetings. To honor and encourage research of high quality, the Endocrine Society Awards for Distinguished Research in Endocrinology and in Diabetes have been established since 2002. The EST is a founding member of AFES and AFES as a group also is a member of the International Society of Endocrinology (ISE). It is the intention of EST to increase collaboration with other endocrine societies around the globe. 53

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Assoc Prof. Joseph Lopez Personal Information Nationality: Malaysia Position: Last position: Head of Department; presently retired Department: Department of Biomedical Sciences Organization: MAHSA University Email: jblopez2611@gmail.com Educational background & professional experience (in sequence of the latest year) Jan 2006-Nov 2014 Dept of Biomedical Sciences, MAHSA Head of Department University, Kuala Lumpur 1973-2005 Institute for Medical Research Research Officer Research Interests 1. Environmental impact of clinical laboratories 2. Tumour marker utility 3. Laboratory quality Publications (5 important publications – latest sequence) 1. Lopez JB, Hoyaranda E and Priatman The First Green Diagnostic Centre and Laboratory Building in Indonesia. eJIFCC. 2016; 27:84-87 2. Lopez JB and Badrick T. Proposals for the mitigation of the environmental impact of clinical laboratories. Clin Chem Lab Med 2012; 50(9):1559–1564. 3. Lopez JB. Recent developments in the first detection of hepatocellular carcinoma (Review). Clin Biochem Rev 2005; 26: 65-79. 4. Lopez JB and Chin LP. Plasma homocysteine reference values of adult Malaysians from three ethnic groups. Clin Chim Acta 2004, 340: 235-238 5. Lai CL Leslie Charles (Chairman of committee and in alphabetical order), Cheong SK, Goh KL, Hapizah Nawawi, Leong CF, Lim KH Albert, Loh CS, Lopez JB, Subramaniam R and Sivanesratnam V. Clinical Practice Guidelines on Serum Tumour Markers. Malays J Pathol 2003; 25: 83-105

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Successful Organization of an International Medical Conference JOSEPH LOPEZ APFCB Immediate Past President and Chair, APFCB Congresses and Conferences Committee

Medical conferences are an important means by which health professionals keep abreast with the latest developments in their fields. The number of annual health conferences worldwide runs into the 1000s. The competition for participants and sponsors is therefore intense. Most international health conferences belong to international medical bodies, which then delegate the organization to their members. The organization begins with the formation of Congress Organizing Committee (COC), which oversees all aspects of the meeting. It may then appoint the scientific organizing committee (SOC), sub-committees for specific activities, a PCO and an external auditor. The core of the scientific programme usually consists of a keynote address, plenary lectures and scientific symposia. Industrysponsored workshops and satellite meetings should be conducted only with SOC approval. There should be an agreement with the PCO clearly defining its role and the financial arrangements involved. The conference should be actively promoted and its website developed early. Revenue streams should be identified and financial expenditure closely monitored. Sponsorship support from industry and especially from the trade exhibition is the biggest source of revenue. The social programme may include the opening and closing events, the conference dinner, an accompanying persons programme and tours. Contingency planning should be factored into the preparations. The audited accounts of the conference should be ready by 6 months after the congress.

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Prof. Toshio Matsumoto, M.D. Personal Information Nationality: Japan Position: Director Department: Fujii Memorial Institute of Medical Sciences Organization: Tokushima University Email: toshio.matsumoto@tokushima-u.ac.jp Educational background & professional experience (in sequence of the latest year) 1974 University of Tokyo School of Medicine MD degree 1978-1981 Yale University School of Medicine Research Fellow Professor and Chair 1996-2014 Department of Medicine & Bioregulatory Sciences, Tokushima University Graduate School of Medical Sciences Research Interests 1 Regulatory mechanism of osteoblast differentiation and bone formation 2 Mechanism of development of cancer-associated bone disease 3 Roles of endocrine and other systems in the development of atherosclerosis Publications (5 important publications – latest sequence) 1. Dong B, Endo I, Ohnishi Y, Kondo T, Hasegawa T, Amizuka N, Kiyonari H, Shioi G, Abe M, Fukumoto S, Matsumoto T. Calcilytic ameliorates abnormalities of mutant calcium-sensing receptor knock-in mice mimicking autosomal dominant hypocalcemia (ADH). J Bone Miner Res 2015;61:727-33, 2. Yoshida S, Aihara K, Ikeda Y, Sumitomo-Ueda Y, Uemoto R, Ishikawa K, Ise T, Yagi S, Iwase T, Mouri Y, Sakari M, Matsumoto T, Takeyama K, Akaike M, Matsumoto M, Sata M, Walsh K, Kato S, Matsumoto T. Androgen receptor promotes sex-independent angiogenesis in response to ischemia and is required for activation of vascular endothelial growth factor receptor signaling. Circulation 2013; 128:60-71 3. Aihara K, Azuma H, Akaike M, Ikeda Y, Sata M, Takamori N, Yagi S, Iwase T, Sumitomo Y, Kawano H, Yamada T, Fukuda T, Matsumoto T, Sekine K, Sat T, Nakamichi Y, Yamamoto Y, Watanabe T, Nakamura T, Oomizu A, Tsukada M, Hayashi H, Sudo T, Kato S, Matsumto T. Straindependent embryonic lethality and exaggerated vascular remodeling in heparin cofactor II-deficient mice. J Clin Invest 2007;117:1486-1489 4. Oshima T, Abe M, Asano J, Hara T, Kitazoe K, Sekimoto E, Tanaka Y, Shibata H, Hashimoto T, Ozaki S, Kido S, Inoue D, Matsumoto T. Myeloma cells suppress bone formation by secreting a soluble Wnt inhibitor, sFRP-2. Blood 2005;106: 3160-3165. 5. Yoshizawa T, Handa Y, Uematsu Y, Takeda S, Sekine K, Yoshihara Y, Kawakami T, Arioka K, Sato H, Uchiyama Y, Masushige S, Fukamizu A, Matsumoto T, Kato S. Mice lacking the vitamin D receptor exhibit impaired bone formation, uterine hypoplasia and growth retardation after weaning. Nature Genet 1997; 16:391-396 56

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Role of Active Vitamin D Compounds in the Treatment of Osteoporosis TOSHIO MATSUMOTO Fujii Memorial Institute of Medical Sciences, University of Tokushima, Tokushima, Japan,

In order to maintain bone remodeling balance, it is important to keep enough Ca absorption. Vitamin D is required to enhance Ca absorption from the gut, but native vitamin D cannot exert its full effect and vitamin D has to be activated to 1,25-dihydroxyvitamin D [1,25(OH)2D] in the kidney to develop its effects. Renal impairment is the main cause of deterioration of the activation of vitamin D. Chronic kidney disease (CKD) develops with aging, causing a reduction in the renal 1,25(OH)2D production and intestinal Ca absorption. Such changes in the elderly cause negative Ca balance, and play a significant role in the pathogenesis of osteoporosis. Therefore, almost all the therapeutic drugs for osteoporosis are accompanied by vitamin D and Ca supplementation in clinical trials. However, because of the poor activation of vitamin D in the elderly, it is more plausible to supply with active vitamin D compounds. In addition, Ca supplementation causes a transient rise in serum Ca, which is associated with an increase in vascular calcification and cardiovascular event. Especially when Ca supplements are given with active vitamin D, excess Ca is absorbed, causing hypercalcemia, hypercalciuria and renal impairment. Thus, Ca supplementation is not recommended with active vitamin D. Among active vitamin D compounds, eldecalcitol increases bone mass and strength by reducing osteoclast formation and bone resorption with an increase in focal bone minimodeling in animals. A 3-year randomized, double-blind, clinical trial demonstrated that eldecalcitol reduces the incidence of vertebral and wrist fractures more strongly than alfacalcidol. The marked reduction in wrist fractures is suggestive of the effect in increasing muscle power and preventing falls. Further studies are needed to clarify its effect on muscle strength and falls.

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Siok Bee Chionh, MBBCh BAO Personal Information Nationality: Singaporean Position: Senior Consultant & Asst Prof (please see below) Department: Division of Endocrinology, University Medicine Cluster Organization: National University Hospital & National University of Singapore Email: Siok_Bee_Chionh@nuhs.edu.sg

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Is It Osteoporosis? SIOK BEE CHIONH Division of Endocrinology, National University Hospital & National University of Singapore

An update will be given on the new criteria proposed by the National Bone Health Alliance Working Group for the clinical diagnosis of Osteoporosis in USA 1, and expands on the current definition of Osteoporosis as a BMD T-score of -2.5 or less. This position paper has been endorsed by the Endocrine Society (USA), the American Society of Bone and Mineral Research and the American Academy of Orthopedic Surgeons, and is expected to be incorporated in the next NOF Clinician’s Guide. In addition, case studies will be used to illustrate that not all cases of Osteoporosis are straightforward post-menopausal or age-related Osteoporosis. There may be secondary or contributory causes to the Osteoporosis, or there may be other causes of low bone mass and fractures, such as Osteomalacia and CKD-Mineral Bone Disease. These additional factors must be addressed for the patient to improve their overall fracture risk.

Sirius ES et al (2014) The clinical diagnosis of osteoporosis: a position statement from the National Bone Health Alliance Working Group. Osteoporos Int 25:1439-1443

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Jung-Fu Chen, M.D. Personal Information Nationality: Taiwan Position: Chief Department: Department of Endocrinology and Metabolism Organization: Kaohsiung Chang Gung Memorial Hospital Email: 0722cjf@adm.cgmh.org.tw Educational background & professional experience (in sequence of the latest year) 2015-NOW Department of Endocrinology and Metabolism of Chief Chang Gung Memorial Hospital at Kaohsiung 2013-2015 Department of Internal Medicine of Chang Gung Vice Chief Memorial Hospital at Kaohsiung 2009-2013 Department of Health Examination of Chang Gung Chief Memorial Hospital at Kaohsiung Research Interests 1. Thyroid 2. DM 3. Osteoporosis Publications (5 important publications – latest sequence) 1. Chen JF, Yang KH, Zhang ZL, Chang HC, Chen Y, Sowa H, Gürbüz S. A systematic review on the use of daily subcutaneous administration of teriparatide for treatment of patients with osteoporosis at high risk for fracture in Asia. Osteoporos Int. 2014 Aug 20. 2. Hwang JS, Tsai KS, Cheng YM, Chen WJ, Tu ST, Lu KH, Hou SM, Yang SH, Cheng H, Lai HJ, Lei S, Chen JF*. Vitamin D status in non-supplemented postmenopausal Taiwanese women with osteoporosis and fragility fracture. BMC Musculoskeletal Disorders. 2014 Jul 28;15:257. 3. Hwang JS, Liou MJ, Ho C, Lin JD, Huang YY, Wang CJ, Tsai KS, Chen JF*. The effects of weekly alendronate therapy in Taiwanese males with osteoporosis. J Bone Miner Metab. 2010 May;28(3):328-33. 4. Loke SS, Yang KD, Chen KD, Chen JF. Erosive esophagitis associated with metabolic syndrome, impaired liver function, and dyslipidemia. World J Gastroenterol. 2013 Sep 21;19(35):5883-8. 5. Hwang JS, Chan DC, Chen JF, Cheng TT, Wu CH, Soong YK, Tsai KS, Yang RS. Clinical practice guidelines for the prevention and treatment of osteoporosis in Taiwan: summary. J Bone Miner Metab. 2014 Jan; 32(1): 10-6.

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Osteoporosis and Diabetes JUNG FU CHEN Department of Endocrinology and Metabolism, Kaohsiung Chang Gung Memorial Hospital

Today Diabetes mellitus has eventually become a medical mass phenomenon in majority parts of the world. Affluent access to a high-carbohydrate/high-fat diet in combination with denser energy uptake has led to a pandemic of the metabolic syndrome and T2DM .Rationally vascular complications include nephropathy, neuropathy and retinopathy as well as ischemic heart disease, peripheral vascular disease and stroke. Now novelty diabetes related osteoporotic fractures becomes as a newly but lonely ignored diabetic complication. Using Taiwan’s National Health Insurance Research Database (2000– 2008), It did showed during 652,530 person-years of follow-up, there were 12,772 newly diagnosed fracture cases. The incidences of for people with diabetes and without were 24.2 and 17.1 per 1,000 person-years, respectively (P < 0.0001). Compared with people without diabetes, the adjusted HR of was 1.66 for people with diabetes. The ORs of post deep wound infection, septicemia, and mortality associated with diabetes were 1.34 , 1.42 ,and 1.27 respectively. Generally Hip risk is significantly increased in both type 1 (RR 6.3) and type 2 (RR 1.7) diabetes. Type 1 diabetes with poor control is dually associated with severe osteoporosis, but in type 2 diabetes, an increased risk of hip fracture is seen despite higher BMD. In some large observational studies showed femoral neck BMD T-score and derived the WHO Risk Assessment Tool (FRAX) score were precisely associated with hip and no spine fractures. But the application of FRAX in diabetics can’t really assess and do under-estimate the ominous diabetes related fracture .Prevention strategies for people with diabetes are just the same as for the general population and include adequate vitamin D and calcium supplementation with regular aerobic weight loading exercise. For patients with type 2 diabetes with fracture risk factors, thiazolidinediones and sodium–glucose cotransporter 2 inhibitors should be avoided possibly as revealing associated with a higher risk of fracture and also current antiosteoporotic fracture agents are given as indicated.

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th Annual Meeting of March 19-20, 2016 The Endocrine Society and The Diabetes Association of the R.O.C. (Taiwan)

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Primary Aldosteronism: Unilateral or Bilateral Disease? ANDRÉ LACROIX Professor of Medicine, Division of Endocrinology, Centre hospitalier de l’Université de Montréal (CHUM).

Primary aldosteronism (PA) is responsible for 6-13% of human hypertension and increases cardiovascular and other morbidities rates compared to essential hypertension. The most frequent causes of PA include bilateral idiopathic hyperplasia (IHA, 60-70%), and unilateral aldosteronoma (APA, 30-40%). This distinction was recently challenged by the findings of zona glomerulosa nodular hyperplasia adjacent to APA. Currently, adrenal vein sampling (AVS) is recommended to differentiate lateralized from bilateral sources of PA. However, many of its technical aspects and interpretation remain controversial between the various AVS expert centers. We present the results of our experience using bilateral simultaneous AVS with samples taken before and after ACTH bolus. ACTH administration is useful to increase selectivity ratios. A discordance of lateralization between basal (LR≥2) and post-ACTH (LR≥4) values was observed in 28% of cases, mostly lateralized cases basally that became bilateral post ACTH. Examining both basal and post-ACTH values are important for the interpretation of AVS. The basal CL ratio using absolute aldosterone level of non-dominant adrenal vein/periphery was superior to the commonly used aldosterone/cortisol (A/C) ratios to identify the frequent occurrence of contralateral hyperplasia even in lateralized cases and to predict outcome after unilateral adrenalectomy.

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Prof. Sihoon Lee, M.D., Ph.D. Personal Information Nationality: Korea Position: Associate Professor of Medicine Department: Internal Medicine/Endocrinology and Metabolism Organization: Gachon University School of Medicine 嘉泉大學校醫科大學 Email: shleemd@gachon.ac.kr Educational background & professional experience (in sequence of the latest year) 2006-2008 Diabetes Unit/NCCAM/NIH Postdoc Fellow 2005-2006 Internal Medicine/Yonsei University College of Medicine Clinical Fellow 2004-2005 Tissue Engineering/University of Tokyo Visiting Fellow 1998-2003 Internal Medicine/Severance Hospital Intern and Resident 2000-2005 Yonsei University Graduate School Ph.D 1992-1998 Yonsei University College of Medicine M.D Research Interests 1. Genomics and Translational Research of Adult and Pediatric Endocine diseases 2. Gene editing using CRISPR-CAS and its therapeutic application 3. Animal model development of human diseases Publications (5 important publications – latest sequence) 1. Lee S et al. Homozygous [Cys25]PTH(1_84) Mutation that Impairs PTH/PTHrP Receptor Activation Defines a Novel form of Hypoparathyroidism. J Bone Miner Res 30:1803-1813, 2015 2. Lee S et al. Identification and characterization of C106R, a novel mutation in the DNA-binding domain of GCMB, in a family with autosomal dominant hypoparathyroidism. Clin Endocrinol (Oxf) 76:625-633, 2012 3. Lee S et al. Current Approaches for Assessing Insulin Sensitivity and Resistance In Vivo: advantages, limitations, and appropriate usage. Am J Physiol Endocrinol Metab 294:E15-E26, 2008 4. Lee S et al. Protein Kinase C-ζ phosphorylates Insulin Receptor Substrate-1, -3, and -4, but not -2: isoform specific determinants of specificity in insulin signaling. Endocrinology 149:2451-2458, 2008 5. Lee S et al. Expression of Vasopressin V1b, V2 Receptors in the Adrenal Gland in the Familial Adrenocorticotropin-Independent Macronodular Adrenal Hyperplasia. Clin Endocrinol (Oxf) 63:625-630, 2005

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Patients Who have Taught Me a Lot: Personal Experiences of Rare Adrenal Diseases SIHOON LEE 李是勳 Department of Internal Medicine/Endo and Laboratory of Genomic and Translational Medicine, Gachon University School of Medicine, Incheon, Korea Department of Bioengineering, Graduate School of Engineering, The University of Tokyo, Tokyo, Japan

Adrenal glands play pivotal role in maintaining our daily life and it is only after we lose their functional regulation either hyper- or hypo-that we acknowledge their considerable significance in essential contribution to our vitality. As many other physiology has been unveiled through investigating pathologic conditions, abundant knowledge and understanding of adrenal physiology was accumulated by seeing the patients. I am not exceptional with this regard. The first patients who came to my scope were sisters, both suffering from overt Cushing syndrome aroused by bilateral macronodularadrenal hyperplasia (BMAH). Provocation tests in vivo suggested that AVP promoted cortisol secretion through vasopressin V1a as well as V1b and V2 receptors. RT-PCR analysis revealed an abnormal cDNA expression of vasopressin V1b and V2 receptors, none of which is known to be normally expressed in the adrenal glands. These results suggest that the expression of ectopic vasopressin V1b and V2 receptors may be involved in the etiology of AIMAH, at least in the case of the sibling patients. Furthermore, meningiomas were incidentally found in these two patients, and we postulated the possibility that they may be involved in the pathogenesis of BMAH which has been supported by accumulating both clinical and molecular genomic evidences. With regard to the second BMAH patient who required the successive completion adrenalectomy due to hypersecretion of cortisol in the remaining adrenal gland detected during follow up, I will focus on the importance of understanding molecular pathophysiology of BMAH in terms of medical treatment with specific antagonizing agents or agonists as a possible alternative to bilateral adrenalectomy. This may help to avoid life-long steroid replacement therapy and poor quality of life. Moreover, I would like to share several other experiences on adrenal patients in this lecture.

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Prof. Shih-Hua Lin, M.D. Personal Information Nationality: Taiwan, Republic of China Position: Superintendent Department: Tri-Service General Hospital Organization: National Defense Medical Center Email: l521116@gmail.com Educational background & professional experience (in sequence of the latest year) 1981 - 1988 National Defense Medical Center, Bachelor Taipei, Taiwan 2011/12/1–2012/11/30 Department of Medicine, Tri-Service Director General Hospital 2012/12/1–2015/1/15 Tri-Service General Hospital Deputy Superintendent 2013/6/1-2015/1/15 2015/1/16-2015/12/31 2016/1/16-present

National Defense Medical Center Army Medical Affair Tri-Service General Hospital

Associate Dean Director Superintendent

Research Interests 1. Clinical acid-base and electrolyte disorders and metabolism 2. Genetic diagnosis in inherited renal tubular disorder 3. Disease-causing transgenic mice model Publications (5 important publications – latest sequence) 1. Mechanism of thyrotoxic periodic paralysis. J Am Soc Nephrol 2012; 23: 985-988. 2. Genotype, phenotype and follow-up in Taiwanese patients with Gitelman’s syndrome. J Clin Endocrinol Metab 2012; 97: E1478-1482. 3. Defective NCC phosphoryation impairs its stability and prevents pseudohypoaldosteronism type II. J Am Soc Nephrol 2013; 24: 1587-1597. 4. Novel KCNJ 5 mutations in sporadic aldosterone-producing adenoma reduce Kir3.4 membrane abundance. J Clin Endocrinol Metab 2015; 100: E155-163. 5. Novel susceptibility gene for non-famililal periodic paralysis. Neurology 2016 (in press)

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Clinical and Genetic Heterogeneity of Aldosterone-Producing Adenoma in Taiwan

台灣醛固酮分泌腺瘤的臨床與基因多型性 SHIH-HUA LIN 林石化 Department of Medicine, Division of Nephrology, Tri-Service General Hospital, Taipei, Taiwan, R.O.C. 三軍總醫院內科部腎臟科

Aldosterone secretion is physiologically stimulated by angiotensin II and high plasma potassium (K ) concentration, which transiently depolarize the membrane potential of adrenal zona glomerulosa cells, increase intracellular calcium (Ca2+) concentration and then aldosterone synthesis. Acquired primary aldosteronism is mainly caused by bilateral adrenal hyperplasia and aldosterone-producing adenoma (APA, some referred to Conn’s syndrome) with unclear pathogenesis. Recently, a series of genetic studies have identified somatic mutations in several genes, including KCNJ5 (G-protein sensitive Kir3.4 channel), CACNA1D (Cav1.3 Ca2+ channel), ATP1A1 (Na+, K+ ATPase subunit α-1), and ATP2B3 (Ca2+ ATPase) genes, indicating the genetic heterogeneity in APA. Most of these mutations caused small cation (e.g. Na+) leak and persistently depolarized membrane potential of adrenal cells, leading to unstoppable aldosterone synthesis in APA. In our Taiwanese APA cohort, heterozygous KCNJ5 somatic mutations were identified in 37.8% patients, CACNA1D 4% and ATP1A1 1%. In those with KCNJ5 mutations, female predominance and higher disease severity, reflecting by younger onset age, larger tumor size and lower nadir serum potassium level, were noted. Two novel mutations (R115W, E246G), resulted in a hypofunctional Kir3.4 channel due to impaired membrane trafficking in vitro and reduced its overall expression in vivo. Patients with CACNA1D or ATP1A1 mutations had a milder disease with smaller tumor size and older onset age. Futhermore, adrenalectomy cured hypertension in 64% of APA patients and significantly improved hypertension in the remainders in our cohorts. Of note, 29% of APA patients developed hyperkalemia after adrenalectomy and associated with impaired renal function and longer duration of hypertension. In conclusion, APA has been linked to the heterogeneous genes controling membrane potential, intracellular calcium, aldosterone synthesis and adrenocortical growth and differentiation. These diverse gene associations may thus contribute to the various disease severity and final outcome of APA. +

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th Annual Meeting of March 19-20, 2016 The Endocrine Society and The Diabetes Association of the R.O.C. (Taiwan)

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Yin Chian Kon, M.D. Personal Information Nationality: Singapore Position: Senior Consultant Department: Endocrinology Organization: Tan Tock Seng Hospital, Singapore Email: Winston_Kon@ttsh.com Educational background & professional experience (in sequence of the latest year) 2015 AACE Elected Fellow 2014-2016 Residency Advisory Committee for Endocrinology, Member Ministry of Health, Singapore 2014-2016 Endocrine & Metabolic Society of Singapore President 2013-2014 Chapter of Endocrinology, Academy of Medicine, Chairman Singapore 2007 Royal College of Physicians, Edinburgh, UK Elected Fellow 2005-current Endocrinology/Tan Tock Seng Hospital Senior Consultant 2004-current Reproductive Endocrinology/Kadang Kerbau Hospital Visiting Consultant 2003 Academy of Medicine, Singapore Elected Fellow Research Interests 1. Thyroid, Graves' disease 2. Diabetes 3. Reproductive Endocrinology Publications (5 important publications – latest sequence) 1. YC Kon, Hawkins R. Falsely Elevated Serum Testosterone Levels in a Young Adult Female with Polycystic Syndrome (PCOS) and Left Adrenal Adenoma. JAFES 2013;28:159-162 2. Stanley Lam, Huiling Liew, Hong Tar Khor, Rinkoo Dalan, Yin Chian Kon, Michelle Jong, Daniel EK Chew, Melvin Khee Shing leow. VIPoma in a 37-year-old man. Lancet 2013;382: 832 3. Jonathan T. Tan, Daniel P. K. Ng, Siti Nurbaya, Sandra Ye, Xiu Li Lim, Helen Leong, Lin Tze Seet, Wei Fong Siew, Winston Kon, Tien Yin Wong, Seang Mei Saw, Tin Aung, Kee Seng Chia, Jeannette Lee, Suok Kai Chew, Mark Seielstad, and E. Shyong Tai. Polymorphisms Identified through Genome-Wide Association Studies and Their Associations with Type 2 Diabetes in Chinese, Malays, and Asian-Indians in Singapore J. Clin. Endocrinol. Metab. Jan 2010; 95: 390 - 397. 4. SC Lim, JJ Liu, HQ Low, NG Morganthaler, Y Li, LY Yeoh, YS Wu, SK Goh, CY Chionh, SH Tan, YC Kon, PC Soon, YM Bee, T Subramaniam, CF Sum, KS Chia. Microarray analysis of multiple candidate genes and associated plasma proteins for nephropathy secondary to type 2 diabetes among Chinese individuals Diabetologia 2009; 52: 1343-1351 5. WH Yong, YC Kon, C Rajasoorya, JPN Goh, HS Howe. Bilateral Adrenal Haemorrhage and Evan’s syndrome as the Initial Presentation of Antiphospholipid Syndrome From Systemic Lupus Erythematosus. Endocrinologist 2010; 20(2): 66-68 70

CV & Abstract S4-1

Rapid Responder Graves’ Thyrotoxicosis: Clinical Features, Clinical Implications KON YIN CHIEN, WINSTON President, Endocrine and Metabolic Society of Singapore Senior Consultant, Dept of Endocrinology, Tan Tock Seng Hospital, Singapore

Some patients with newly diagnosed Graves’ thyrotoxicosis unexpectedly develop hypothyroxinemia after a short course of treatment with a moderate dose of anti-thyroid drug (ATD). The diagnostic characteristics and clinical course of a case series of such patients with Graves’ hyperthyroidism whose serum fT4 concentration decreased drastically within 1 to 3 months of initiating treatment with oral carbimazole (CMZ) 5 to 20 mg daily will be described, and clinical implications examined.

The

th Annual Meeting of March 19-20, 2016 The Endocrine Society and The Diabetes Association of the R.O.C. (Taiwan)

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Prof. Pei-Wen Wang, M.D. Personal Information Nationality: Taiwan Position: Professor Department: Department of Internal Medicine and Nuclear Medicine Organization: Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan Email: wangpw@adm.cgmh.org.tw Educational background & professional experience (in sequence of the latest year) 1969 -1976 College of Medicine, National Taiwan University, Taiwan MD 1976-1979 National Taiwan University Hospital, Taipei, Taiwan Residency in Internal Medicine Chang Gung Memorial Hospital, Taipei, Taiwan 1979-1981 Chang Gung Memorial Hospital, Taipei, Taiwan Fellow in Endocrinology and Nuclear Medicine 1984-1985 McGill University and Montreal General Hospital, Canada Research Fellow in Endocrinology 1996-1997 Stanford University School of Medicine, U.S.A Postdoctoral Fellow in Endocrinology and Metabolism 1981-present Chang Gung Memorial Hospital, Kaohsiung, Taiwan Attending Physician Research Interests 1. Thyroid cancer 2. Nuclear endocrinology 3. Mitochondria dysfunction in Diabetes Publications (5 important publications – latest sequence) 1. Liou CW, Chen JB, Tiao MM, Weng SW, Huang TL, Chuang JH, Chen SD, Chuang YC, Lee WC, Lin TK, Wang PW. Mitochondrial DNA coding and control region variants as genetic risk factors for type 2 diabetes. Diabetes. 2012 Oct;61(10):2642-51 2. H uang IC, Chou FF, Liu RT, Tung SC, Chen JF, Kuo MC, Hsieh CJ, Wang PW. Long-term outcomes of distant metastasis from differentiated thyroid carcinoma. Clin Endocrinol (Oxf). 2012 Mar;76(3):439-47 3. Weng SW, Kuo HM, Chuang JH, Lin TK, Huang HL, Lin HY, Liou CW, Wang PW. Study of insulin resistance in cybrid cells harboring diabetes-susceptible and diabetes-protective mitochondrial haplogroups. Mitochondrion. 2013 Aug 13. 4. Hsieh CJ, Wang PW. Sequential changes of serum antithyroglobulin antibody levels are a good predictor of disease activity in thyroglobulin-negative patients with papillary thyroid carcinoma. Thyroid. 2014 Mar;24(3):488-93 5. Wang PW, Kuo HM, Huang HT, Chang AY, Weng SW, Tai MH, Chuang JH, Chen IY, Huang SC, Lin TK, Liou CW. Biphasic response of mitochondrial biogenesis to oxidative stress in visceral fat of diet-induced obesity mice. Antioxid Redox Signal. 2014 Jun 1;20(16):2572-88.

CV & Abstract S4-2

Management of Radioactive Iodine-Refractory Differentiated Thyroid Carcinoma - Data from Kaohsiung Chang Gung Memorial Hospital

高雄長庚紀念醫院對放射碘治療無效之分化型甲狀腺癌之處理經驗 PEI-WEN WANG 王佩文 Department of Internal Medicine and Nuclear Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan 高雄長庚醫院新陳代謝科及核子醫學科暨長庚大學醫學院

Most cases of differentiated thyroid cancer (DTC) are curable with thyroidectomy and radioactive iodine (RAI) ablation. However, tumors may develop RAI-resistance due to progressive de-differentiation over time and lose the ability to uptake iodine. The criteria for RAI-refractory disease remain somewhat controversial. The 2015 American Thyroid Association guidelines include four categories of patients: 1) ones whose tumors do not concentrate 131I since the first discovery of the disease; 2) ones whose tumors lose the ability to concentrate 131I after previous evidence of uptake; 3) ones whose tumors’ uptake of 131I is retained in some lesions but not in others; 4) ones whose metastatic diseases progress despite significant uptake of 131I. The presence of RAI-refractory structurally evident DTC depends on the findings of a post-therapy 131I whole body scan combined with other imaging modalities, such as CT, MRI or 18FDG PET/CT. In our series, about 15% of DTC patients developed RAI-refractory diseases. Risk factors include old age, invasive tumor behavior, and metastases detected by 18F-FDG. In patients with distant metastasis, those who went into remission had a lower mean cumulative dose of 131I than those who did not (297 ± 195mCi vs. 618 ± 381mCi). One patient developed leukemia after receiving a cumulated 131 I activities of 900mCi. In patients who are not cured despite several treatment courses and whose diseases remain stable, it is unclear whether further 131I therapy should be abandoned (particularly after receiving ≥600mCi). Locally directed treatments (surgery and EBRT in our series) have been beneficial to selected patients. Remission was successfully achieved by surgical removal of neck or mediastinum LNs that concentrate only 18FDG but not 131I. Local treatment modalities other than surgery (stereotactic radiation and thermal ablation) are considered potential treatments to be developed in our future practice. Kinase inhibitor therapy has been used in patients with metastatic, progressive, symptomatic and threatening diseases, which were not amendable by locally directed treatments. Patients with RAIrefractory DTCs that are asymptomatic, stable or minimally progressive, and do not have indication for directed therapy are monitored with watchful waiting.

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th Annual Meeting of March 19-20, 2016 The Endocrine Society and The Diabetes Association of the R.O.C. (Taiwan)

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Prof. Takashi Akamizu, M.D., Ph.D. Personal Information Nationality: Japanese Position: Professor and Chairman, PhD, MD Department: The First Department of Medicine Organization: Wakayama Medical University Email: akamizu@wakayama-med.ac.jp Educational background & professional experience (in sequence of the latest year) 2010 Wakayama Medical University Professor and Chairman 2007 Faculty of Medicine, Kyoto University Professor 2001 Faculty of Medicine, Kyoto University Associate Professor Research Interests 1. Pathogenesis and pathophysiology of autoimmune thyroid disease, particularly Graves’ diseas 2. Translational research on ghrelin 3. Thyroid storm Publications (5 important publications – latest sequence) 1. Takeshima K, Inaba H, Furukawa Y, Nishi M, Yamaoka H, Miyamoto W, Ota T, Doi A, Kawashima H, Ariyasu H, Wakasaki H, Furuta H, Nakao T, Sasaki H, Akamizu T. Elevated serum immunoglobulin G4 levels in patients with Graves' disease and their clinical implications. Thyroid. 2014 Apr;24(4):736-43. 2. Akamizu T, Satoh T, Isozaki O, Suzuki A, Wakino S, Iburi T, Tsuboi K, Monden T, Kouki T, Otani H, Teramukai S, Uehara R, Nakamura Y, Nagai M, Mori M; Japan Thyroid Association. Diagnostic criteria, clinical features, and incidence of thyroid storm based on nationwide surveys. Thyroid. 2012 Jul;22(7):661-79 3. Akamizu T, Kangawa K. The physiological significance and potential clinical applications of ghrelin. Eur J Intern Med. 2012 Apr;23(3):197-202. 4. Akamizu T, Matsuda F, Okuda J, Li H, Kanda H, Watanabe T, Honjo T, Mori T. Molecular analysis of stimulatory anti-thyrotropin receptor antibodies (TSAbs) involved in Graves' disease. Isolation and reconstruction of antibody genes, and production of monoclonal TSAbs. J Immunol. 1996 Oct 1;157(7):3148-52. 5. Akamizu T, Ikuyama S, Saji M, Kosugi S, Kozak C, McBride OW, Kohn LD. Cloning, chromosomal assignment, and regulation of the rat thyrotropin receptor: expression of the gene is regulated by thyrotropin, agents that increase cAMP levels, and thyroid autoantibodies. Proc Natl Acad Sci U S A. 1990 Aug;87(15):5677-81.

CV & Abstract S4-3

IgG4-Related Thyroid Diseases TAKASHI AKAMIZU President, AOTA; Vice President, Japan Endocrine Society; President, Japan Thyroid Association The First Department of Medicine, Wakayama Medical University, Japan

IgG4 related disease (IgG4-RD), which is characterized by the infiltration of IgG4-positive plasmacytes into multiple organs induces tissue fibrosis and organ dysfunction. In addition to the involvement of the pancreas, the lacrimal gland, salivary gland, biliary duct, retroperitoneal tissue and etc., endocrine organs can also be involved in this disease A relationship between IgG4-RD and endocrine diseases has been reported, including thyroid diseases, pituitary diseases and diabetes mellitus. In this symposium, recent development in studies on IgG4-related thyroid diseases will be discussed, including our research on Graves’ disease, Hashimoto’s thyroiditis and Riedel’s thyroiditis. References 1. Takeshima K, Inaba H, Ariyasu H, Furukawa Y, Doi A, Nishi M, Hirokawa M, Yoshida A, Imai R, Akamizu T. Clinicopathological features of Riedel’s thyroiditis associated with IgG4-related disease in Japan. Endocr J. 2015 62(8):725-31 2. Takeshima K, Ariyasu H, Inaba H, Inagaki Y, Yamaoka H, Furukawa Y, Doi A, Furuta H, Nishi M, Akamizu T. Distribution of serum immunoglobulin G4 levels in Hashimoto’s thyroiditis and clinical features of Hashimoto’s thyroiditis with elevated serum immunoglobulin G4 levels. Endocr J. 2015 62(8):711-7 3. K hosroshahi A, Wallace ZS, Crowe JL, Akamizu T, et al. International Consensus Guidance Statement on the Management and Treatment of IgG4-Related Disease. Arthritis Rheumatol. 2015 Jul;67(7):1688-99 4. Takeshima K, Inaba H, Furukawa Y, Nishi M, Yamaoka H, Miyamoto W, Ota T, Doi A, Kawashima H, Ariyasu H, Wakasaki H, Furuta H, Nakao T, Sasaki H, Akamizu T. Elevated serum immunoglobulin G4 levels in patients with Graves’ disease and their clinical implications. Thyroid. 2014 Apr;24 (4):736-43

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th Annual Meeting of March 19-20, 2016 The Endocrine Society and The Diabetes Association of the R.O.C. (Taiwan)

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Liang-Yu Lin, M.D., Ph.D. Personal Information Nationality: Taiwan, R.O.C. Position: Attending physician Department: Division of Endocrinology and Metabolism, Department of Medicine Organization: Taipei Veterans General Hospital Email: linly@vghtpe.gov.tw Educational background & professional experience (in sequence of the latest year) 2008Division of Endocrinology and Metabolism/ Attending physician Taipei Veterans General Hospital 2015Faculty of medicine/National Yang-Ming Assistant Professor University 2003-2007 Division of Endocrinology and Metabolism/ Fellow Taipei Veterans General Hospital Research Interests 1. Diabetes vasculopathy 2. Dyslipidemia 3. General endocrine disorder Publications (5 important publications – latest sequence) 1. Chang LH, Hwu CM, Chu CH, Won JG, Kwok CF, Lin HD, Chen HS, Lin YC, *Lin LY: The Ankle Brachial Index Exhibits Better Association of Cardiovascular Prognosis than Non-High-Density Lipoprotein Cholesterol in Type 2 Diabetes. Am J Med Sci 2016 (accepted). 2. Chang LH, Chu CH, Lin HD, Kwok CF, Won JG, Chen HS, *Lin LY: The ankle brachial index is associated with prognosis in patients with diabetic kidney disease. Diabetes Res Clin Pract 2015;108:316-322. 3. Lin LY, Huang CC, Chen JS, Wu TC, Leu HB, Huang PH, Chang TT, Lin SJ, *Chen JW. Effects of pitavastatin versus atorvastatin on the peripheral endothelial progenitor cells and vascular endothelial growth factor in high-risk patients: A pilot prospective, double-blinded, randomized study. Cardiovasc Diabetol 2014;13(1):111. 4. Huang CJ, Chen PJ, Chang JW, Huang DF, Chang SL, Chen SA, Jap TS, *Lin LY: Amiodaroneinduced Thyroid Dysfunction in Taiwan: a retrospective cohort study. Int J Clin Pharm 2014;36(2):405-11. 5. Liu PY, #Lin LY, Lin HJ, Hsia CH, Hung YR, Yeh HI, Wu TC, Chen JY, *Chien KL, *Chen JW: Pitavastatin and Atorvastatin Double-Blind Randomized ComPArative Study among HiGh-Risk Patients, Including ThOse with Type 2 Diabetes Mellitus, in Taiwan (PAPAGO-T Study). PLoS One. 2013 Oct 1;8(10):e76298.

CV & Abstract S5-1

Drug-Induced Thyroid Dysfunctions

藥物引起的甲狀腺功能異常 LIANG-YU LIN 林亮羽 Division of Endocrinology and Metabolism, Taipei Veterans General Hospital 臺北榮民總醫院內分泌新陳代謝科

“Iatrogenic” means any adverse condition in a patient resulting from treatment by a physician, nurse, allied health professional. Iatrogenic disorders are an important cause of morbidity, mortality, and admission to hospital in the worldwide. Normal thyroid secretion depends on thyroid-stimulating hormone (TSH), which is inhibits by thyroid hormones and stimulated by endogenous thyrotropinreleasing hormone (TRH). Similar to many other organs, the thyroid gland may be affected by various drugs, often used for the treatment of non-thyroid disorders. Drug may affect thyroid function via different mechanisms, including thyroid hormone production, storage, transport and metabolism offering numerous targets for drug interventions. Usually, the effect of pharmacotherapy is observed more frequently and is stronger in case of the presence of the concomitant disorder of thyroid gland. The drugs which may cause thyrotoxicosis include interferon, molecular-targeted agents, amiodarone and so on. Those which cause hypothyroidism included immune checkpoint therapy, lithium, and iodine etc. which inhibit thyroid hormone synthesis and secretion, and dopamine etc. which block TSH secretion. An understanding of the proposed mechanisms of these drug interactions and their evaluation and differential diagnosis is helpful in the interpretation of the findings associated thyroid disorders and in establishing the correct treatment. Therefore, it is important to review the present state of knowledge on the influence of various drugs on the hypothalamic-pituitary-thyroid axis and concern the diagnosis and treatment of drug induced thyroid dysfunctions.

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th Annual Meeting of March 19-20, 2016 The Endocrine Society and The Diabetes Association of the R.O.C. (Taiwan)

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Prof. Yoon-Sok Chung, M.D., Ph.D. Personal Information Nationality: South Korea Position: President of the Korean Society of Osteoporosis (KSO) Department: Endocrinology and Metabolism Organization: Ajou University School of Medicine Email: yschung@ajou.ac.kr Educational background & professional experience (in sequence of the latest year) 2001 ~ 2002 Loma Linda University, California, USA Visiting Professor 1994 ~ 1997 Yonsei University, Seoul, Korea Ph.D. 1982 ~ 1988 Yonsei University, Seoul, Korea M.D. Research Interests 1. Osteoporosis 2. Bone Metabolism 3. Osteoblast Publications (5 important publications – latest sequence) 1. Q uantification of Visceral Fat Using Dual-Energy X-Ray Absorptiometry and Its Reliability According to the Amount of Visceral Fat in Korean Adults. J Clin Densito 18(2):192-197, 2015 (Corresponding author) 2. Insulin is inversely associated with bone mass, especially in the insulin-resistant population. The Korea and US National Health and Nutrition Examination Surveys. J Clin Endocrinol Metab 99:1433-1441, 2014 (Corresponding author) 3. The prevalence of osteoporosis in Korean adults aged 50 years or older and the higher diagnosis rates in women who were beneficiaries of a national screening program: The Korea National Health and Nutrition Examination Survey 2008-2009. J Bone Miner Res. 27:1879-1886, 2012 (Corresponding author) 4. The importance of morphometric radiographic vertebral assessment for the detection of patients who need pharmacological treatment of osteoporosis among postmenopausal diabetic Korean women. Osteoporos Int. 23:2099-2105, 2012 (Corresponding author) 5. Poncirin prevents bone loss in glucocorticoid-induced osteoporosis in vivo and in vitro. J Bone Miner Metab. 30:509-516, 2012 (Corresponding author)

CV & Abstract S5-2

Type 2 Diabetes Mellitus and Osteoporosis YOON-SOK CHUNG Department of Endocrinology and Metabolism, Ajou University School of Medicine, Suwon, South Korea

Fragility fracture rate is increased in type 2 diabetic patients despite of higher bone mineral density (BMD) than non-diabetic control subjects. Vertebral fractures are usually asymptomatic; therefore, radiologic evaluation might be considered for diabetic patients. Fracture Risk Assessment Tool (FRAX) has been used for prediction of 10-year probability of major osteoporotic fractures. Bone quality may more contribute to the increased risk of osteoporotic fractures in patients with type 2 diabetes than bone mass. Hip geometry, cortical porosity, and trabecular bone score (TBS) have been studied as bone quality parameters by imaging in type 2 diabetes mellitus (T2DM). We performed the study comparing TBS, BMD, and FRAX score in the association of vertebral fractures in T2DM Korean postmenopausal women. TBS and FRAX as well as BMD may be good supplementary tools to predict osteoporotic fractures.

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th Annual Meeting of March 19-20, 2016 The Endocrine Society and The Diabetes Association of the R.O.C. (Taiwan)

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Prof. Won Bae Kim, M.D., Ph.D. Personal Information Nationality: Republic of Korea Position: Director, Division of Endocrinology & Metabolism Department: Department of Internal Medicine Organization: Asan Medical Center Email: kimwb@amc.seoul.kr Educational background & professional experience (in sequence of the latest year) 1987 Seoul National University, College of Medicine 2008 Asan Medical Center, Dept. of Internal Med & Professor Ulsan Univ college of Medicine 2015 Korean Thyroid Association Chief of directors Research Interests 1. Cancer biology : cancer cell metabolism & mechanism of invasion & metastasis 2. Translational research : Thyroid cancer 3. Clinical research : Thyroid cancer & Hyperthyroidism Publications (5 important publications – latest sequence) 1. Features Predictive of Distant Metastasis in Papillary Thyroid Microcarcinomas. Thyroid. 2016 2. Alpha lipoic acid inhibits proliferation and epithelial mesenchymal transition of thyroid cancer cells. Mol Cell Endocrinol. 419:113-23, 2016 3. Usefulness of NRAS codon 61 mutation analysis and core needle biopsy for the diagnosis of thyroid nodules previously diagnosed as atypia of undetermined significance. Endocrine. 2015 Nov 7. 4. Recent changes in the clinical outcome of papillary thyroid carcinoma with cervical lymph node metastasis. J Clin Endocrinol Metab. 100:3470-3477, 2015 5. Sub-Classification of Lateral Cervical Lymph Node Metastasis in Papillary Thyroid Carcinoma by Pathologic Criteria. PLoS One. 2015 Jul 17;10(7):e0133625.

CV & Abstract S5-3

Alpha Lipoic Acid Inhibits Proliferation and Epithelial- Mesenchymal Transition of Thyroid Cancer Cells WON BAE KIM Department of Internal Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea

The naturally occurring short-chain fatty acid, α-lipoic acid (ALA) is a powerful antioxidant which is clinically used for treatment of diabetic neuropathy. Recent studies suggested the possibility of ALA as a potential anti-cancer agent, because it could activate adenosine monophosphate activated protein kinase (AMPK) and inhibit transforming growth factor-β (TGFβ) pathway. In this study, we evaluate the effects of ALA on thyroid cancer cell proliferation, migration and invasion. We performed in vitro cell proliferation analysis using BCPAP, HTH-83, CAL-62 and FTC-133 cells. ALA suppressed thyroid cancer cell proliferation through activation of AMPK and subsequent downregulation of mammalian target of rapamycin (mTOR)-S6 signaling pathway. Low-dose ALA, which had minimal effects on cell proliferation, also decreased cell migration and invasion of BCPAP, CAL62 and HTH-83 cells. ALA inhibited epithelial mesenchymal transition (EMT) evidently by increase of E-cadherin and decreases of activated β-catenin, vimentin, snail, and twist in these cells. ALA suppressed TGFβ production and inhibited induction of p-Smad2 and twist by TGFβ1 or TGFβ2. These findings indicate that ALA reduces cancer cell migration and invasion through suppression of TGFβ production and inhibition of TGFβ signaling pathways in thyroid cancer cells. ALA also significantly suppressed tumor growth in mouse xenograft model using BCPAP and FTC-133 cells. This is the first study to show anti-cancer effect of ALA on thyroid cancer cells. ALA could be a potential therapeutic agent for treatment of advanced thyroid cancer, possibly as an adjuvant therapy with other systemic therapeutic agents.

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th Annual Meeting of March 19-20, 2016 The Endocrine Society and The Diabetes Association of the R.O.C. (Taiwan)

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Yen Hsiang Chang, M.D. Personal Information Nationality: TAIWAN Position:Attending physician Department: Nuclear Medicine Organization: Kaohsiung Chang Gung Memorial Hospital Email: changyh@cgmh.org.tw Educational background & professional experience (in sequence of the latest year) 2000-2008 National Taiwan University Bachelor of Medicine 2009-2013 Department of Nuclear Medicine, Kaohsiung Resident Chang Gung memorial hospital 2014 DecDepartment of Nuclear Medicine, Kaohsiung Attending Physician Chang Gung memorial hospital Research Interests 1. Nuclear Medicine 2. Thyroid Cancer Publications (5 important publications – latest sequence) 1. Y-H Chang, C-C Hsu, P-W Wang, Y-C Huang: Left ventricular dyssynchrony occurs frequently in patients with coronary artery disease. Ann Nucl Med Mol Imaging. 2013 Dec; 26:140-148. 2. Y-H Chang, P-W Wang: “T-shaped” sign: a false-positive I-131 uptake in the stenum mimicking thyroid cancer metastasis. Ann Nucl Med Mol Imaging. 2013 Sep; 26: 113-115.

CV & Abstract S5-4

Impact of 18F-FDG PET/CT on the Clinical Outcome and Management of Differentiated Thyroid Cancer Patients with Positive 131I Whole Body Scan and Elevated Thyroglobulin

正子電腦斷層造影對於甲狀腺癌患者預後以及處置之影響：針對放射性碘顯像且甲狀腺球蛋白皆為陽性者之探討。 YEN-HSIANG CHANG 張雁翔 Department of Nuclear Medicine, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung City, Taiwan, R.O.C. 高雄長庚醫院核子醫學科

Background: 18F-fluoro-deoxyglucose positron emission tomography and computed tomography (18F-FDG PET/CT) has a role in the surveillance of patients with differentiated thyroid cancer (DTC), especially those with thyroglobulin (Tg)-positive and a negative radioiodine whole body scan (131I WBS). Its usefulness in DTC patients with positive 131I WBS had seldom been discussed. The aim of this study was to evaluate the impact of 18F-FDG PET/CT on the management and clinical outcome of DTC patients with positive 131I WBS and elevated Tg. Methods: From 2005 to 2013, a total of twenty-seven patients with DTC were retrospectively evaluated. All of the patients had undergone total or near-total thyroidectomy followed by radioiodine ablation. During the follow-up, the patients with positive 131I WBS and a concurrent detectable stimulated-Tg underwent an 18F-FDG PET/CT study within one year. Patients with any other form of malignancy were not included in this study. The 18F-FDG PET/CT findings were analyzed, with disease progression as a primary endpoint. Results: Among the 27 patients, twenty (74%) patients had positive 18F-FDG PET/CT findings. The sensitivity, specificity, and diagnostic accuracy of 18F-FDG PET/CT for detecting recurrent/ residual lesions were 86.3%, 80%, and 85%, respectively. In 12 (44%) patients, 18F-FDG PET/CT provided additional information than 131I WBS and conventional imaging; 8 (30%) of them resulted in a change of clinical management. Twelve (44%) patients experienced disease progression after 18F-FDG PET/CT during followup. The maximal standard uptake value (SUVmax) of the lesion with strongest 18F-FDG uptake was significantly higher in patients with progression than those without progression. Patients with lesion SUVmax over 4.5 were suggestive for disease progression with sensitivity of 90% and specificity of 87.5%. Of the 7 (26%) patients with negative 18F-FDG PET/CT result, 6 patients achieved undetectable Tg at the end of follow-up. Conclusion: In DTC patients with positive 131I WBS and an elevated Tg, 18F-FDG PET/CT plays a complementary role to conventional follow-up methods. Lesion SUVmax provides prognostic information in identifying DTC patients with disease progression, while a negative 18F-FDG PET/CT result suggests a favorable prognosis. 83

The

th Annual Meeting of March 19-20, 2016 The Endocrine Society and The Diabetes Association of the R.O.C. (Taiwan)

EL-1

Prof. Chiou-Fen Lin, Ph.D. Personal Information Nationality: Taiwan Position: Professor Department: School of Nursing Organization: National Taipei University of Nursing and Health Sciences Email: evalin@ntunhs.edu.tw Educational background & professional experience (in sequence of the latest year) 2007 / 02-2012 /07 School of Nursing, Taipei Medical University Associate Professor 2008 / 08-2012 /07 Department of Nursing, Shuang Ho Hospital, Director Nursing Taipei Medical University Research Interests 1. The plan of retention and recruiting consultation for nurses in hospital 2. Flow of Nursing Manpower in Taiwan 3. Development of the Quality Nursing Work Environment (QNWE) in Taiwan Publications (5 important publications – latest sequence) 1. Chiou-Fen Lin*, Meei-Shiow Lu, Hsiu-Ying Huang (2015). The Psychometric Properties and the Development of the Indicators of Quality Nursing Work Environment (IQN-WE) in Taiwan. Journal of Nursing Research, (103.8.accept) (SCI, Ranking: 57/110, 51.8%, IF=0.970) 2. Mei-I Wang, Ching-Chiu Kao, Chiou-Fen Lin*(2015). The EPCOR model: a model to promote successful implementation of evidence-based nursing in the hospital-based health care setting. Journal of Nursing Research, 23(1), 15-24.[SCI] (68/107, 63.6%, IF=0.844) 3. Chiou-Fen Lin, Hsiu-Ying Huang, Meei-Shiow Lu(2013). The Development of Nursing Workforce Allocation Standards for Acute Care General Wards in Taiwan‧Journal of Nursing Research, 21(4), 298-306. [SCI] (68/107, 63.6%, IF=0.844) 4. Chiou-Fen Lin, Meei-Shiow Lu, Chun-Chih Chung, Che-Ming Yan(2010). The establishment of an ethical guideline for genetic testing through citizen consensus via the Internet in Taiwan . Journal of Medical Internet Research, 12(4), e47, 1-10. [SCI] (2/69,2.9%, IF=3.924) 5. Chiou-Fen Lin, Meei-Shiow Lu, Chun-Chih Chung, Che-Ming Yang(2010).A comparison of Problem-based Learning and conventional teaching in nursing ethics education. Nursing Ethics. 17(3), 373-382. [SCI] (24/72, 33.3%, IF=1.075)

CV & Abstract EL-1

Gender and Medicine

性別與醫學 CHIOU-FEN LIN 林秋芬 Professor, School of Nursing, National Taipei University of Nursing and Health Sciences, and Nursing Consultant, Department of Nursing, Shuang Ho Hospital, Taipei Medical University. 國立臺北護理健康大學護理學系教授、臺北醫學大學 ‧ 部立雙和醫院護理顧問

性別可以分為生物性別 (sex) 和社會性別 (gender)，人類的生物性別 (Sex) 差異，是指男性和女性生理上的先天差異。出生時就分為男性與女性，因生理結構上不同的區分，也稱為性徵或生理性別；社會性別 (Gender) 差異，是指社會上對於男性與女性的期待角色不同，而發展出不同的性別特質稱之，乃透過社會化過程，定義女性和男性人格特質，包括其行為舉止、態度、角色、價值觀…等。生理性別是先天俱來，然社會性別可能透過學習、刻意改變、多元文化和時空…… 等因素影響決定。為何我們需要談性別議題，因為人類發展指數 (HDI，Human Development Indicator)、性別發展指數 (GDI，Gender Development Indicator)、性別權力測度 (GEM，Gender Empowerment Measurement)、性別落差指標 (GGI，Gender Gap Indicator ) 都是國家競爭力的重要指標。而過去醫學的性別觀點是非常薄弱的，因此需要談談病人是否需要有性別的差別待遇以及醫療性別主流化的作法。 Sex can be divided into biological gender (sex) and social gender (gender). The human biological gender (sex) means the physiological differences between men and women. Men or women, because the distinction between different physical structure, also known as biological sex or sexuality. Social gender (gender) means the social expectations lead for male and female differences by the socialization process. The definition of male and female personality, including behavior, attitudes, roles, values ... etc. Biological sex is born nature, however, the social gender is affecting and decided by the factors, such as, learning, deliberately changing, multi-cultural diversity ...etc. We have to discuss this Sex topic, as the key national competitiveness indicators are Human Development Indicator (HDI), Gender Development Indicator (GDI), Gender Empowerment Measure (GEM), Gender Gap Index (GGI). In the past, medical gender perspective is very weak, which causing we made this topic to study whether there are gender differences in patient needs when medical treatment and also find out the mainstreaming gender practices in medical field.

The

th Annual Meeting of March 19-20, 2016 The Endocrine Society and The Diabetes Association of the R.O.C. (Taiwan)

EL-2

Fan-Fen Wang, M.D. Personal Information Nationality: Taiwan Position: Attending Physician Department: Division of Endocrinology and Metabolism, Department of Medicine Organization: Yang-Ming Branch, Taipei City Hospital Email: doc1298d@yahoo.com.tw Educational background & professional experience (in sequence of the latest year) 1989-1996 Medicine / Taipei Medical College M.B.(M.D.) 2004-2010 Institute of Clinical Medicine / National YangM.S. Ming University, Taipei, Taiwan, R.O.C. 2003Division of Endocrinology and Metabolism, Attending Physician Department of Medicine, Yang-Ming Branch, Taipei, City Hospital Research Interests 1. Iodine nutrition 2. Cushing’s syndrome 3. Polycystic ovary syndrome Publications (5 important publications – latest sequence) 1. Tang KT, Wang FF, Pan WH, Lin JD, Won GS, Chau WK, Lin HD, Hsieh YT. Iodine status of adults in Taiwan 2005–2008, 5 years after the cessation of mandatory salt iodization. J Formos Med Assoc DOI: http://dx.doi.org/10.1016/j.jfma.2015.06.014 2. Tang KT, Wang FF, Fu SS, Braverman LE, Lin JD, Won GS. A Simple Microplate Method with Improved Low Iodine Concentration Sensitivity in Urinary Iodine Measurement. Thyroid, 2015;25(10):1173-1174. 3. Wang FF, Tang KT, Yen YS, Ho DMT, Yang AH, Huang CI, Lin HD, Won JGS. Plasma corticotrophin response to desmopressin in patients with Cushing’s disease correlates with the expression of vasopressin receptor 2, but not with that of vasopressin receptor 1 or 3, in their pituitary tumours. Clin Endocrinol, 2012; 76:253-263. 4. Wang FF, Chang YH, Pan CC, Tu DG, and Won JGS. Unusual Visualization of an Adrenal Carcinoma on NP-59 Scintiscan. J Formos Med Assoc 2006; 105(4):340-345. 5. Wang FF, Su CC, Chang YH, Pan CC, Tang KT, Jap TS, Lin HD, Won JGS. Primary adrenal lymphoma manifestating as adrenal incidentaloma. J Chin Med Assoc. 2003 Jan;66(1):67-71.

CV & Abstract EL-2

Assessment and Interpretation of Iodine Nutrition of Populations: Experiences from the Recent Taiwan Surveys

群體碘營養之評估與解讀 : 近期台灣研究之經驗 FAN-FEN WANG 王繁棻 Division of Endocrinology and Metabolism, Yang-Ming Branch, Taipei City Hospital, Taipei, Taiwan, ROC 臺北市立聯合醫院陽明院區新陳代謝科

Iodine is a micronutrient essential for synthesis of thyroid hormones. Eliminating iodine deficiency disorders (IDD) has been an integral component of public health strategies of many countries since 1990. In 1993, WHO and UNICEF officially recommended universal salt iodization as the main strategy to achieve the elimination of iodine deficiency. Both the proportion of households using iodized salt and the population iodine status are indicators of the sustainable elimination of IDD. Four methods are generally recommended for assessing adequacy of iodine nutrition in populations: urinary iodine concentration (UIC), the goiter rate, serum TSH, and serum thyroglobulin. UIC is the most practical biomarker for recent iodine nutrition, and criteria have been established for classifying degrees of iodine nutrition. The median rather than the mean is used to measure central tendencies. Presenting the distribution of UIC in a population helps determine if there is a large proportion with either very low or very high values. It is important not to misinterpret the different percentages to define the number of individuals who are deficient. Mandatory salt iodization program in Taiwan was first launched in 1976, but ceased in 2003. The state of iodine nutrition in Taiwan is changing, related to the flooding of noniodized salt to the market, and the dietary variations including the increased consumption of processed food and the decreased levels of salt intake. Monitoring programs reaching vulnerable groups (pregnant women and newborns), surveys including both UIC and household coverage with iodized salt, combined with proper interpretation of the data, allow accurate definition of population’s iodine nutrition status, which is necessary to achieve a state of iodine adequacy. This presentation will describe the iodine nutrition data from the recent Taiwan surveys, and the application of the interpretation methods suggested by the WHO using these data as examples.

The

th Annual Meeting of March 19-20, 2016 The Endocrine Society and The Diabetes Association of the R.O.C. (Taiwan)

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DIETARY INTAKE IN ELDERLY TYPE 2 DIABETES SUBJECTS IN TAIWAN 1

HSIU-YUEH SU, 2MIN-SU TZENG, 3SHU-TI CHIOU, 4NENG-CHUN YU, 5 WAYNE H-H SHEU 1

Department of Dietetics, Taipei Medical University Hospital, Taipei, Taiwan, R.O.C.; 2Department of Nutritional Science, Fu Jen Catholic University, Taipei, Taiwan, R.O.C.; 3Health Promotion Administration, Ministry of Health and Welfare, Taiwan, R.O.C.; 4Yu Neng-Chun Diabetes Clinic, I-Lan County, Taiwan, R.O.C.; 5Division of Endocrinology and Metabolism, Department of Internal Medicine, Taichung Veterans General Hospital, Taichung, Taiwan, R.O.C.

This was a cross-sectional survey commissioned by Health Promotion Administration, Ministry of Health and Welfare, and conducted by Taiwanese Association of Diabetes Educators in year 2011. In brief, type 2 diabetic subjects who regularly visited the same Diabetes Health Promotion Institute for at least one year were invited by a method of one per every 5 consecutive visitors. Every 5 enrolled subjects were asked to fill the semi-quantitative food frequency questionnaire (FFQ). The categories listed in FFQ included a total of 10 food categories and 83 types of food. We compared elderly group (≥65 years old, n=285, with age 72.6±5.1 years (mean±SEM), and the adult group (<65 years old, n=392, with age 54.4±8.0 years). The body mass index of the elderly group was lower than the adult group (25.3±3.7 vs. 26.4±4.4 kg/m2, p<0.05). Values of SBP, DBP, fasting glucose, PPG, HbA1c, total cholesterol, LDL-cholesterol and triglyceride were not different between elderly and adult diabetes. There were no differences between calorie intake (1856.0±630.8 vs. 1965.1±619.3 kcal/day, p=0.80) and protein intake (59.5±25.0 vs. 64.9±23.9 gm/day, p=0.47) while cholesterol intake were significantly lower in elderly diabetes subjects (158.7±123.6 vs. 206.4±156.5mg/day, p<0.01) than adults diabetes. In general, nutrients intake were lower in women than men with the cholesterol intake reached statistically significant. The percentages of those who attained the ABC goals in the elderly group were 12.3% compared with 8.6% in the adult group (p=0.413). In conclusion, nutrients intake of the elderly diabetic group are lower than the adult group. Further careful monitoring and ensure adequacy nutrients intake while maintain good diabetes control in elderly patients are clearly needed.

Abstract O2-2

S ITAGLIPTIN AND RISK OF HEART FAILURE HOSPITALIZATION IN PATIENTS WITH TYPE 2 DIABETES AND END STAGEENAL DISEASE ON DIALYSIS: A POPULATION-BASED COHORT STUDY 1,2

YI-CHIH HUNG, 3,4CHE-CHEN LIN, 1,2WEI-LUN HUANG, 5MAN-PING CHANG, 1,6 CHING-CHU CHEN 1

Division of Endocrinology and Metabolism, Department of Medicine, China Medical University Hospital, Taichung, Taiwan, R.O.C.; 2BDepartment of Medicine, China Medical University, Taichung, Taiwan, R.O.C.; 3Management Office for Health Data, China Medical University Hospital, Taichung, Taiwan, R.O.C.; 4 Department of Public Health, China Medical University, Taichung, Taiwan, R.O.C.; 5Department of Nursing, School of Health, National Taichung University of Science and Technology, Taichung, Taiwan, R.O.C.; 6School of Chinese Medicine, China Medical University, Taichung, Taiwan, R.O.C.

Context: The incidence of heart failure hospitalization (HHF) after taking sitagliptin in type 2 diabetes (T2DM) patients with end stage renal disease (ESRD) on dialysis is unclear because these patients are usually excluded from randomized clinical trials. Objective: To assess sitagliptin treatment and the risk of HHF among T2DM patients receiving dialysis. Design and Setting: In this population-based cohort study from the Taiwan National Health Insurance Research Database, we identified individuals taking sitagliptin between 2009 and 2011 and randomly selected a control cohort matched by age, sex, and index year at a 1:4 ratio. Multivariable Cox proportional hazards regression analysis was used to evaluate HHF risk. Participants: Patients with T2DM and ESRD on dialysis, not taking metformin, acarbose, saxagliptin, vildagliptin, linagliptin, or thiazolidinediones. Intervention: Taking sitagliptin for the first time. Main Outcome: HHF Results: The overall incidence of HHF was higher in the sitagliptin cohort than in the control cohort (1142 vs.806 per 10000 person-years; adjusted hazard ratio (HR): 1.50, 95% CI =1.18-1.89). There was a significant trend towards increased HHF risk associated with increased sitagliptin dose (p for trend < 0.01). Subjects at greater risk of HHF were those without severe hypoglycemia, on ACE inhibitors treatment, having history of heart failure, or receiving hemodialysis. Conclusions: Use of sitagliptin was associated with an increased risk of HHF in patients with T2DM and ESRD on dialysis, especially in those without severe hypoglycemia, on ACE inhibitors treatment, with prior heart failure, or receiving hemodialysis.

The

th Annual Meeting of March 19-20, 2016 The Endocrine Society and The Diabetes Association of the R.O.C. (Taiwan)

O2-3

ALTERED MITOCHONDRIAL DYNAMICS, BIOGENESIS, AND BIOENERGETICS IN CYBRID CELLS HARBORING A DIABETESSUSCEPTIBLE MITOCHONDRIAL DNA HAPLOGROUP 1

CHENG-FENG TSAO, 1PEI-WEN WANG, 1HSIAO-MEI KUO, 1SHAO-WEN WENG, 3 JIIN-HAUR CHUANG, 2TSU-KUNG LIN, 2CHIA-WEI LIOU, 1CHING-YI LIN 1

Department of Internal Medicine, 2Department of Neurology and 3Department of Surgery , Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung 833, Taiwan

Aims: The advantage of using a cytoplasmic hybrid (cybrid) model to study the genetic effects of mitochondria is that the cells have the same nuclear genomic background. We previously demonstrated the independent role of mitochondria in the pathogenesis of insulin resistance (IR). However, exactly how the mitochondria respond to insulin stimulation in insulin-resistant cells remains unanswered. Methods: We compared mitochondrial dynamics, biogenesis, and bioenergetics between cybrid cells harboring diabetes-susceptible (B4) and diabetes-protective (D4) mitochondrial haplogroups, especially the responses before and after insulin stimulation. Results: Diabetes-susceptible cybrid B4 showed a more fragmented mitochondrial network, impaired mitochondrial biogenesis (mtDNA copy number) and bioenergetics (mitochondrial ATP concentrations and Oxygen consumption rate (OCR)), and a high expression of fission-related molecules (mitochondrial fission 1 protein (FIS1) and dynamin-related protein 1 (DRP1)), with a trend towards pro-fission. Upon insulin stimulation, increases in network formation, mitochondrial DNA (mtDNA) content, and ATP production were observed only in the diabetes-protective cybrid D4. Insulin promoted a pro-fusion dynamic status in both cybrids, but the trend was greater in D4 cells than in B4 cells. In cybrid B4, the imbalance between mitochondrial dynamics and impaired biogenesis and bioenergetics were significantly improved in response to antioxidant treatment. Further, the increase in the mitochondrial network and mtDNA content and ATP concentration in response to insulin developed after antioxidant treatment. Conclusions: Diabetes-susceptible mtDNA variants are themselves resistant to insulin. These genetic variants, mediating ineffective mitochondrial respiration, affect multifarious mitochondrial and cellular functions, including an imbalance in mitofusion and mitofission, decreased biogenesis and impaired bioenergetics.

Abstract O2-4

Tumor mass effects of headache, visual field defects, and hypopituitarism are main clinical manifestation of nonfunctional pituitary macroadenoma. Usually, various degrees of deficiency in different kinds of pituitary hormones were reported in the cases with hypopituitarism. Here, we reported two cases of nonfunctional pituitary macroadenoma presenting as panhypopituitarism and hyponatremia. Case 1: A 65 year-old male was sent to ER with persistent vomiting, epigastric dull pain since last night. Other symptoms included chest tightness, vertigo, and headache. Physical examination revealed BP 145/79mmHg, PR 95/min, BT 36.5°C, E4V5M6, BW 76 kg, acute ill-looking, and weakness. Laboratory data showed serum Na: 119 mmol/L, random cortisol: 1.17 ug/dL(N:4.3~22.40), ACTH: 11.7 pg/mL(N:7.9-47.1), Free T4: 0.58 ng/dL (N:0.61-1.48), TSH: 1.35μIU/mL (N:0.34-5.6). Under the impression of adrenal insufficiency with hyponatremia, hydR.O.C.ortisone and intravenous fluid supplement were given. Followed up laboratory data showed cortisol: 14.8 ug/dL, free T4: 0.47 ng/dL, and Na: 139mmol/L. Brain MRI showed a 1.6 cm mass lesion in the sella turcica. He was referred to neurosurgeon for the further management. Case 2: A 66-year-old female came to OPD f for the chief problem of vomiting for one day. She was currently treated with prednisolone 5 mg 2 # qd and eltroxin 100ug by her doctor in another hospital. At our OPD, the findings of physical examination were unremarkable. Her laboratory data during admission period showed Na110mmol/L, K4.0 mmol/L, Cl87 mmol/L, cortisol(AM): 2.45ug/ dL, ACTH: 22.5pg/mL(N:9~52), TSH: 3.37μIU/mL (N: 0.4~4), T3: 0.73 ng/mL (N: 0.84-1.72), and T4: 3.39μg/dL (N: 4.5-12.5). Other endocrine hormone tests showed LH:0.84 mIU/mL(N:1.1~77), FSH: 5.85 mIU/mL(N:1.2~21), Prolactin: 24.4 ng/mL (N:3~20), E2: 5.04 pg/mL(N:30~330), and progesterone: 0.09 ng/mL(N:0.25~23). Brain MRI showed a pituitary macroadenoma. After operation, she was treated with levothyroxine 100ug qd ac. Baseline serum cortisol (AM) and ACTH level were within normal limit. In conclusion, hyponatremia may be the main clinical manifestation of patients with nonfunctional pituitary macroadenoma with panhypopituitarism.

The

th Annual Meeting of March 19-20, 2016 The Endocrine Society and The Diabetes Association of the R.O.C. (Taiwan)

O2-5

Background and aim: Current diabetic ketoacidosis (DKA) guidelines are sometimes too complicated and it is difficult for the residents to strictly adhere every step of recommendation on duty(no ensuring 0.02U/Kg/hour insulin by adding intravenous glucose, even stopped insulin infusion when near hypoglycemia, resulting ketogenesis recurs and increases cerebral edema risk). In this study, we retrospectively evaluated the outcome of our simplified modification of DKA guideline. Methods: We give continuous intravenous “12U insulin mix with 50g glucose” (without using pump) to replace insulin pump. Suggested infusion rate is about 4U/hour at initial 6 hours(loading), then 2U/hour for subsequent 24 hours(maintainance), to ensure >0.02U/Kg/hour insulin in most patients. Oral intake is encouraged if no contraindication(give prokinetic if poor intake), so we can inject more subcutaneous insulin to ensure daily insulin ≥0.8U/Kg/day. Oral intake is also for dietary potassium and phosphate supplement. Prophylactic potassium supplement is given to reduce the severity and frequency of hypokalemia, for renal failure patients, can start with empirical safe dose(safe dose[meq] before follow serum K level next time = [5.3 - current serum K] * 0.236 * Body weight[Kg]) to ease the worry of iatrogenic hyperkalemia. We present a typical DKA case who experienced common suboptimal treatment(poor adherence to guideline) prescribed by duty physicians in emergency department for 4 hours, and was shifted to our simplified protocol then. Results: After one day of treatment, beta-Hydroxybutyric acid was rechecked, DKA already subsided(from>8.0mmol/L to 0.1mmol/L), serum bicarbonate had been normalized too. Her DKA subsided simply due to adequate insulin supplement, without strict glucose control with insulin pump(which need to check one touch per 1~2 hour to titrate infusion rate), thus, patient can sleep well under check one touch only 4 times a day, cost and nursing loading(for check one touch) also become lower. DKA doesn’t recur under daily insulin ≥0.8U/Kg/day as long as adequate oral intake. Conclusions: The simplified modification ensures the adherence of continuous adequate intravenous insulin by giving intravenous glucose at the same time. DKA subside without insulin pump thus improves patients’ sleep quality, decreases cost and nursing loading.

Abstract O2-6

Background: Whether hyperthyroidism affects clinical outcome of thyroid cancer remains controversial. Objectives: We retrospectively compare the clinical characters and outcome of thyroid cancer patients with euthyroidism (ETC) or hyperthyroidism (HTC). Methods: From Oct. 1987 to Nov. 2013, 546 cases of thyroid cancer were retrospectively reviewed in a Northern Taiwan medical center. Clinical outcome was compared according to the histopathological diagnosis and the presence or absence of hyperthyroidism. Results: Among the 546 thyroid cancer patients, 182 (33.3%) were HTC and 364 (66.7%) were ETC. All patients were confirmed to be papillary thyroid cancer post-operatively. The mean age was 39.1 (range, 22-72) year-old in HTC and 39.2 (range ,15-73) year-old in ETC. Female predominance was found equally in HTC and ETC (86.3% vs 82.4%, P=0.251). The tumor size was significantly smaller in HTC than in ETC ( 1.2 ± 1.2 vs 2.4 ± 1.6 cm, P<0 .001). While cancer mortality rate was low in both HTC and ETC (2.7% vs 4.7%, P=0.281); disease-free rate (DFR) was higher in HTC than in ETC (93.4% vs 84.1%, P=0.002). Persistently elevated anti-thyroglobulin antibody (ATA) was found in 18 of 149 (12.1%) disease-free HTC even after total thyroidectomy. Conclusions: In this series, papillary cancer was the only cancer type. Although HTC has significantly higher DFR, it can be attributed to the higher incidence of micR.O.C.arcinomas in HTC since no difference of DFR was found when micR.O.C.arcinoma was excluded from both groups. Finally, not a small proportion (12.1%) of HTC has persistently high ATA postoperatively.

The

th Annual Meeting of March 19-20, 2016 The Endocrine Society and The Diabetes Association of the R.O.C. (Taiwan)

O2-7

COMPARISON OF CLINICAL CHARACTERISTICS AND OUTCOME OF MICRO- AND MACRO-ALBUMINURIA IN TYPE 2 DIABETES WAI-KIN CHAN, SZU-TAH CHEN Division of Endocrinology and Metabolism, Department of Internal Medicine, Chang Gung Memorial Hospital, Chang Gung University, Taiwan, R.O.C.

OBJECTIVE: This study retrospectively compared the clinical characteristics and outcome of diabetic nephropathic patients with micro- (30-299 mg/L) or macro- (above 300mg/L) albuminuria. RESEARCH DESIGN AND METHODS: 56 type 2 diabetic nephro 特 pathic patients were retrospectively reviewed from 2013/01 to 2016/01. All patients were treated with oral anti-diabetes drugs/insulin, angiotensin II receptor blockers (ARB) or angiotensin-converting enzyme inhibitors (ACEI). Clinical data including urine albumin creatinine ratio (UACR), glycosylated hemoglobin (HbA1c), systolic blood pressure (SBP) and estimated glomerular filtration rate(eGFR) were analyzed. Patients were divided into micro- and macro-albuminurine groups according to their latest amount of spot urine albumin. All data were analyzed with Generalized Estimating Equation (GEE) to evaluate the changes in SBP, HbA1c, UACR and eGFR. RESULTS: Our study includes 23 (41%) micro- and 33 (59%) macro-albuminuria patients aged 60.21±10.46 and 66.13±11.27 year-old, respectively. After adjusting age and sex factors, both groups showed a trend of increasing UACR during the 3-year follow-up period. Although both group has similar HbA1c (microalbuminuria: 7.74%±1.85 VS macroalbuminuria: 8.11%±1.45) and SBP, only the macroalbuminuria group showed a statistical significance (B=210.501, SE=88.72, p=0.018) in UACR increment with a significant higher slope (B=540.828, SE=211.88, p=0.011). Deterioration of renal function as demonstrated by decreasing eGFR was found significantly in both groups (microalbuminuria: B=-6.310, SE=1.9212, P=.001; macroalbuminuria: B=-4.879, SE=1.2949, P<0.0001) without significant difference in their decreasing slope (B=-12.06, SE=9.30, p=0.195). CONCLUSIONS: Although the rate of exacerbated urinary protein excretion was enhanced in the macroalbuminuria group, the rate of decreasing eGFR was similar in both micro- and macroalbuminuria groups during the 3-year follow-up period.

Abstract O2-8

INTERACTION BETWEEN STRA6 SIGNALING SUPPRESSION AND MITOCHONDRIAL DYSFUNCTION INDUCES KIDNEY APOPTOSIS AND FIBROSIS IN DIABETES 1

CHAO-HUNG CHEN, 2KUN-DER LIN, 3TUSTY-JIUAN HSIEH, 2YU-LI LEE, 2MEIYUEH LEE, 2,4PI-JUNG HSIAO, 2,4SHYI-JANG SHIN 1

Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, 80708, Taiwan; 2Division of Endocrinology and Metabolism, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, 80708, Taiwan; 3Department of Medical Genetics, School of Medicine, College of Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, 80708, Taiwan; 4Department of Internal Medicine, School of Medicine, College of Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, 80708, Taiwan

Mitochondrial dysfunction and oxidative stress are shown as an initiating trigger to induce diabetic nephropathy. We recently reported that the suppression of RBP4 receptor cascades involves dyslipidemia-induced arterial and renal damage. We thus investigated whether the suppression of RBP4 receptor signaling could interact with mitochondrial dysfunction to cause apoptosis and fibrosis in diabetes. In the kidneys of streptozotocin(STZ)-induced diabetes and high glucose(HG)cultured HEK cells, RBP4 receptor(STRA6), MnSOD, caspase 3 and collagen 1 protein as well as apoptotic cells increased, but CRBP1, RARα, ATP synthase, and cytochrome c expression as well as mitochondrial potential decreased. By immunoprecipitation method using STRA6 antibody, we found the binding activity of RBP4 on STRA6 in diabetes and HG-cultured cells were markedly reduced. ROS inhibitor and MnSOD gene transfection reversed above alterations in HG-cultured cells. MnSOD silencing significantly reversed STRA6, CRBP1 and RARα expression but didn’t affect caspase3 and collagen 1 in HG-cultured cells. Interestingly, CRBP1 gene transfection reversed the suppression of ATP synthase, cytochrome c, the increase of caspase 3 and collagen 1 protein and mRNA expression, but increased binding activity of RBP4 with STRA6, and expression of RARα in HG-cultured cells. This study indicates that interaction between the suppression of RBP4 Receptor signaling and mitochondrial dysfunction induces kidney apoptosis and fibrosis in diabetes. KEY WORDS: RBP4; STRA6; MnSOD; MITOCHONDRIAL DYSFUCTION; KIDNEY

The

th Annual Meeting of March 19-20, 2016 The Endocrine Society and The Diabetes Association of the R.O.C. (Taiwan)

O2-9

SULFONYLUREA THERAPY IMPROVED DIABETIC CONTROL IN A MAN WITH NEONATAL DIABETES AND AN ACTIVATING KCNJ11 MUTATION 1,2,3,4,5

YANN-JINN LEE, 1,6CHI-YI HUANG, 1,6WEI-HSIN TING, 2CHIUNG-LING LIN, 1 CHON-IN CHAN 1

Department of Pediatric Endocrinology, MacKay Children’s Hospital; 2Department of Medical Research, MacKay Memorial Hospital Tamsui District; 3Department of Pediatrics, School of Medicine, College of Medicine, Taipei Medical University; 4Institute of Biomedical Sciences, MacKay Medical College; 5 Department of Medicine, MacKay Medical College; 6Department of Nursing, MacKay Medicine, Nursing and Management College

Neonatal diabetes, defined as hyperglycemia occurring in the first few months of life and requiring insulin therapy, is a rare disorder with an estimated incidence of 1 in 400,000 to 500,000 neonates. It may be transient, resolving in a median of 3 months, or permanent, requiring lifelong insulin therapy. A heterozygous activating mutation in the KCNJ11 gene has been identified as a cause of permanent neonatal diabetes (PND). It has been implicated in 30% to 58% of cases of PND in infants under the age of six months. The KCNJ11 gene encodes the Kir6.2 subunit of an ATP-dependent potassium channel (KATP channel) which is critical in regulating insulin secretion in islet β cells. The KATP channel consists of the Kir6.2 pore-forming subunit and SUR (sulfonylurea receptor), the regulatory subunit. Activating mutations of the genes encoding either Kir6.2 or SUR impair KATP channel closure and inhibit insulin secretion, thus causing neonatal diabetes. Sulfonylureas close the KATP channel by an ATP-independent pathway. Their specificity for this molecular defect has led to these agents replacing insulin as the first line therapy in most patients with KCNJ11 mutations. We have reported our experience with successful sulfonylurea treatment in two patients with PND caused by KCNJ11 mutation. Here we reported one more case in whom sulfonylurea therapy could not completely replace insulin treatment. Patient: A 35-year-old man had PND diagnosed at 4 month of age. He was born to a healthy G5P3 mother at 36 weeks of gestation by normal spontaneous delivery. His birth weight was 2400 gm. At 4 months of age he had fever and vomiting and was diagnosed to have juvenile diabetes. Insulin injection was started but parents discontinued it in 2 weeks. At 1 8/12 years of age he was 7.8 kg and had polyuria, polydipsia, polyphagia, constipation, oral ulcer and carbuncle. His urine sugar was 4+ by Benedict test and ketones 3+, and blood glucose 400 mg/dl. Then he was hospitalized and insulin therapy with NPH and regular insulin before breakfast was restarted. One episode of diabetic ketoacidosis when he was 3 1/12 years old because of stop of insulin for 20 days. On insulin therapy, his growth was appropriate for age (50 th percentile). He had mild 96

Abstract developmental delay and psychomotor retardation but no seizures. His HbA1c levels were between 7.6% and 9.6% without obvious hypoglycemia. At the age of 35 years, genetic testing confirmed a c.602G>A (R201H) mutation in the KCNJ11 gene. The insulin dose at that time was 0.81 U/kg/day. A glucose tolerance test showed a C-peptide of 0.29 ng/ml at the peak level. Glibenclamide was started and the dose increased according to Pearson’s switching protocol. The C-peptide concentration was 2.27 ng/ml on the 30th day and 2.44 ng/ml in 1.5 years of glibenclamide therapy. His recent HbA1c was 7.5% at 1.9 mg/kg/day tid of glibenclamide and Novomix 8 U/day. Except 3 bowel movement with soft formed stool, no hypoglycemia had been detected. Hemogram, ALT, AST, BUN, and Cr were within normal limits. Genetic detection of mutation of the KCNJ11 gene: Genomic DNA was isolated from the buffy coat of blood using standard pR.O.C.edures. We first amplified the KCNJ11 gene from 5’ UTR to 3’ UTR, then sequenced the PCR product in both directions through 3 overlapping fragments with 3 nested primer pairs. The primers and PCR conditions were according to Ting et al [PMID 19774848]. The results were compared with data in Genbank (NCBI). The position of a nucleotide is denoted with reference to the A of the starting codon ATG which is +1. Conclusion: Sulfonylurea therapy could improve diabetic control in our patient with PND but not completely replace insulin therapy.

The

th Annual Meeting of March 19-20, 2016 The Endocrine Society and The Diabetes Association of the R.O.C. (Taiwan)

PP-01

Background: Glucocorticoid-induced osteoporosis (GIOP) can result in loss of bone mass and eventually cause fractures of the ribs, long bones and spinal vertebra. Most people of GIOP is because of side effects of iatrogenic glucocorticoid use but not endogeneous glucocorticoid. Severe osteoporosis due to endogenous hypercortisonism was relatively uncommon in the clinical setting, especially for a young adult woman. Therefore, we present a case of a 35-year-old premenopausal woman with severe osteoporosis due to Cushing’s disease who presented with multiple low trauma fractures. Case presentation: A 35-year-old was admitted to our orthopedic department because of left pubic bone fracture after falling from a standing height on a rainy day. She was a well-nourished, normal development, non-pregnant and premenopausal woman who never delivered a child. She ever got multiple rib fractures after slipping on the road one year before admission. She had regular menstrual cycles and denied smoking, alcohol consumption, taking any medication and drug containing ingredients of steroid or Chinese herb. According to her family history, her grandmother had oral cancer and two aunts had breast cancer. Physical exam showed no obvious finding except for overweight based on criteria in Taiwan (body mass index: 26.5 Kg/m2). She was referred to our oncologist’s and endocriologist’s service to rule out pathological fractures. Laboratory results showed 24-hour urine free cortisol (24-h UFC) was 1298.7 ug/day (normal range: 20.9 ~ 292.3 ug/day) with serum adrenocorticotropic hormone (ACTH) 68.4 pg/mL and positive high dose dexamethasone suppression test. Pituitary magnetic resonance imaging (MRI) revealed pituitary microadenoma (7x5x5 mm) in the left-sided pituitary gland. Transsphenoidal surgery for tumor resection was performed and the pathological result showed pituitary tissue with positive immunohistochemical study for ACTH. Severe osteoporosis due to Cushing’s disease was diagnosed definitely. Conclusion: A young adult woman with severe osteoporosis due to Cushing’s disease was a relatively uncommon in our clinical practice. We hope that our experience of this case will remind physicians to be aware of this unusual complication of Cushing’s disease.

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AN ADRENAL ONCOCYTOMA PRESENTING AS CUSHING’S SYNDROME: CASE REPORT AND LITERATURE REVIEW 1

CHIN CHOU YANG, 2CHENG HO CHUNG, 3CHIUNG MING HSU, 4TAO YUAN WANG, 5PEI SHAN TSAI 1

Division of Endocrinology and Metabolism, Mackay Memorial Hospital, Hsinchu, Taiwan; 2Division of Endocrinology and Metabolism, Mackay Memorial Hospital, Taiwan; 3Department of Urology, Mackay Memorial Hospital, Taiwan; 4Department of Pathology, Mackay Memorial Hospital, Taiwan; 5Department of Radiology, Mackay Memorial Hospital, Taiwan

Adrenal oncocytomas are rare and the majorities were benign and non-functional. Of those that produce hormones, Cushing’s syndrome accounts for about 5.8%. We reported a 55-year-old woman presented with Cushing’s syndrome. The final diagnosis was adrenocortical oncocytoma. Case presentation: A 55-year-old woman presented with body edema for 1 week and visited our endocrinologist. She has history of hypertension and type 2 diabetes mellitus with medication control for 2 years (Amlodipine, Valsartan, HydR.O.C.hlorothiazide, Propranolol, Metformin, Glimepiride). She also has history of nonalcoholic steatohepatitis with regular follow-up in our gastroenterology department. Weight gain of 8 kg (81 to 89kg) during past one year was noted. Her height was 153 cm, BMI was 37.5. Blood pressure was 170/111 mm Hg. Heart rate was 102 beat per minutes. She denied chest discomfort, palpitation, headache, or diaphoresis. Physical examination revealed nonpitting edema, centripetal obesity, buffalo hump, and moderate rounding of the face with puffy eye. Overnight 1mg dexamethasone suppression test (DST) revealed positive findings (Table-1). Two-day 2 mg DST was ordered, but the patient lost to follow-up. 9 month later, a right adrenal mass (6.3x4.8cm in size) was incidentally detected in abdominal CT scan during hepatic evaluation (Figure 1). She was then referred back to our endocrine department. The aldosterone, plasma renin activity, potassium and sodium levels were normal (Table-2). Two-day 2 mg DST yielded positive results (Table-3). We also checked urine cortisol and catecholamine (Table-4). The patient was then referred to urology department. Laparoscopic adrenalectomy was performed. The right adrenal gland including the tumor was completely removed. Microscopically, the adrenal gland showed a well-encapsulated mass composed of nests and trabeculae of polygonal cells with abundant granular, eosinophilic cytoplasm. Pleomorphic nuclei were focally seen. Rare mitotic figures were found. On immunohistochemical studies, the tumor cells were Melan-A(+), vimentin(+), synaptophysin (weak+), inhibin-α(weak+), and chromogranin-A(-).Necrosis, capsular invasion, or venous invasion was absent. The final diagnosis was adrenocortical oncocytoma. After discharged, she accepted dexamethasone supplement. Her body weight decreased up to 10% (94 to 83.3 kg within 9 months) and remained stable. There was no edema noted. Her blood pressure was relatively stable (systolic pressure around 120mmHg) under antihypertensive therapy with Valsartan and Amlodipine. 99

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Discussion: Oncocytomas are uncommon and occur most commonly in the kidney (3-10%). These tumors have also rarely been seen in the salivary glands, thyroid gland, pituitary gland, parathyroid gland, lacrimal gland, respiratory tract, and choroid plexus with varying incidence (1). Adrenal oncocytomas are rare and the majorities were benign and non-functional (3). Since the first description in 1986 till 2014, less than 150 cases of adrenal oncocytomas have been reported (4). Usually, these tumors were incidentally discovered and only about 17% were functional (5). Of those that produce hormones, Cushing’s syndrome accounts for about 5.8%, based on the report of 2014 (6). These cases are extremely rare. So far, there are only 5 case of adrenocortical oncocytoma presented with Cushing’s syndrome found in the MEDLINE/PubMed search (MeSH Term: Cushing’s syndrome and adrenal oncocytoma). In our case, a 55 years old woman presented with a right incidental adrenal mass during evaluation for hepatic lesion, which was then removed by laparotomy. Conventional immunophenotype of adrenal oncocytoma are usually positive for vimentin, synaptophysin, inhibin-α, and Melan-A (7). In this case, Melan-A(+), vimentin(+), synaptophysin (weak+), inhibin-α(weak+), and chromogranin-A(-) were found (Figure 2). Together with structural findings of nests and trabeculae of polygonal cells with abundant granular, eosinophilic cytoplasm, a definite diagnosis of adrenocortical oncocytoma was made. Pheochromocytoma should also be taken into consideration in our case because of minimal elevation of urine-norepinephrine, although the patient denied chest discomfort, palpitation, headache, or diaphoresis. However, the CT scan did not revealed marked enhancement of the tumor, which is helpful in differentiating benign oncocytic tumor from pheochromocytoma (11). Histologically, unlike oncocytoma, pheochromocytoma is originating in chromaffin cells. The chromogranin-A was negative in this case. According to above-mentioned results, we excluded the diagnosis of pheochromocytoma. Although adrenocortical oncocytoma has been considered benign and the majority of reported cases had good prognosis, malignant case has ever been reported (8). In this case, a right adrenal mass (6.3x4.8cm in size) with punctate calcification and heterogeneous enhancement was noted. Malignancy should be considered on image study. However, there was no evidence found of being metastatic to other organs and lymph nodes, necrosis or focal invasion to surrounding structures. The tumor margin was also smooth. According to these findings, the case should be considered as benign. Conclusion: Although most of adrenal incidentalomas are clinically silent, careful biochemical evaluations should be performed to differentiate nonfunctional from functional adrenal masses. The possibility of malignancy should also be taken into consideration. Our patient developed Cushing’s syndrome with an adrenocortical oncocytoma, which was confirmed by pathologic findings. Adrenocortical oncocytoma, although extremely rare, should be considered in the differential diagnosis of adrenal incidentaloma.

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A CASE OF ISOLATED HYPOGONADOTROPIC HYPOGONADISM WITH PARTIAL EMPTY SELLA FOLLOWING NORMAL COURSE OF PREGNANCY AND DELIVERY 1

SHUN-HUO WANG, 2KUNG-YU WANG, 1CHIH-YUAN WANG

Division of Endocrinology and Metabolism, Department of Internal Medicine, National Taiwan University Hospital, Taiwan, R.O.C.; 2Department of Internal Medicine, National Taiwan University Hospital, Taiwan, R.O.C.

A 46 year-old woman suffered from secondary amenorrhea after her first time delivery for 18 years. She was pregnant at the age of 28 years. The delivery course was smooth without postpartum hemorrhage or other complication. However, she had only little amount breast milk (<100mL/day) and without recognized menstruation since then on. Hyperprolactinemia was noted later. She was prescribed with Cabergoline for one year, but still did not have further menstruation. Due to no other discomfort, the medication was withdrawn by herself. To our unexpected surprise, she got spontaneous pregnancy without any medication at 32 years old. There were also only little breast milk without recognized menstruation. When she was 37 years old, her left mastitis took place. Documented serum prolactin was 32.0 ng/mL. Brain MRI showed partial empty sella. Cabergoline 0.5 mg weekly was prescribed, and the serum prolactin level decreased to below 0.1 ng/mL one month later with few vaginal spotting. Interestingly, she was pregnant again ! The third time post-partum condition stayed the same, but she refused further Cabergoline treatment. In 2015/04, she visited endocrinologic clinic due to dizziness. Our endocrine profile reported FSH 8.48 mIU/mL, LH 2.91 mIU/mL, E2 21.3 pg/mL, P4 <0.20 ng/mL, IGF-1 117 ng/mL, hGH 0.131 ng/mL, ACTH 15.8 pg/mL(8AM), Cortisol 9.05 μg/dL(8AM). Brain MRI remains partial empty sella. We present a case of isolated hypogonadotropic hypogonadism with partial empty sella following once normal course of delivery with twice more spontaneous pregnancy.

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LY2963016 INSULIN GLARGINE VS LANTUS® INSULIN GLARGINE IN TYPE 2 DIABETES MELLITUS: EAST ASIAN SUBGROUP OF ELEMENT-2 1

CHING-CHU CHEN, 2JU-FEN YEH, 3DAI CHIDA, 4JACEK KILJANSKI, 5LIZA ILAG, 5 ROBYN POLLOM, 5DACHUANG CAO, 6KYUNG WAN MIN 1

Division of Endocrinology and Metabolism, Department of Medicine, China Medical University Hospital, Taichung, Taiwan; 2Eli Lilly, Taipei, Taiwan; 3Eli Lilly Japan K.K., Tokyo, Japan; 4Eli Lilly, Warsaw, Poland; 5Eli Lilly and Company, Indianapolis, USA; 6Eulji General Hospital, Seoul, South Korea

BACKGROUND: The ELEMENT-2 study showed similar efficacy and safety profiles for LY2963016 Insulin Glargine (LY IGlar) and Lantus® Insulin Glargine (IGlar) in 756 patients with type 2 diabetes mellitus (T2DM). These are the results for the East Asian patient subgroup. METHODS: The study included 32 Korean and 21 Taiwanese patients who were insulin-naïve (starting dose: 10 U/day) or receiving IGlar (starting dose: prestudy dose) and followed patient-driven titration (+1 U daily) until fasting blood glucose (BG) was ≤100 mg/dL. Patients received LY IGlar (n=26) or IGlar (n=27) in combination with ≥2 oral antihyperglycemic medications for 24 weeks. Outcomes included change in HbA1c, BG measures, hypoglycemia events (BG ≤70 mg/dL), and safety. RESULTS: The within-group least squares mean (LSM) decrease in HbA1c from baseline to the 24-week endpoint was 1.17% for LY IGlar and 1.13% for IGlar. At the 24-week endpoint, LSM changes in fasting BG were 36.8 mg/dL and 32.6 mg/dL for LY IGlar and IGlar, respectively, daily mean BG was 31.9 mg/dL and 40.0 mg/dL, and the proportion of patients with HbA1c <7% was 57.7% and 46.2%. The mean rate of overall total hypoglycemia events was 20.8 and 14.7 events/patient/year and of nocturnal hypoglycemia events was 4.6 and 4.4 events/patient/year, for LY IGlar and IGlar, respectively. The incidence of treatment-related adverse events and injection-site adverse events was low in both groups. All statistical comparisons were p>.05. There were no statistically significant treatment-by-race interactions for any assessed outcome, indicating that the East Asian subgroup, in general, was similar to the overall population. Given the small numbers of patients in the East Asian subgroup, the numerical results are not intended to be applied to the general East Asian population. CONCLUSIONS: Results from this small subgroup analysis provide insight into treatment outcomes in East Asian patients with T2DM; however, the analysis was not powered to assess similarity of outcomes. DISCLOSURES: This study was supported by Eli Lilly and Company, Indianapolis, IN, USA. This is an encore of an abstract that has been submitted to the Japan Diabetes Society – 59th Annual Meeting, which will take place on 19 – 21 May 2016, in Kyoto, Japan. 102

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THYROTOXIC NEUROPATHY: REPORT OF A CASE 1

SHIH-CHE HUA, 2PO-YEN YEH

Division of Endocrinology and Metabolism, Department of Internal Medicine, St. Martin De Porres Hospital, Taiwan; 2Division of Neurology, Department of Internal Medicine, St. Martin De Porres Hospital, Taiwan

Background: Neuromuscular disorders like acute and chronic myopathy, periodic paralysis, ophthalmoplegia, and rarely myasthenia gravis are known associations of thyrotoxicosis. However, neuropathy in thyrotoxicosis is not frequently recognized. We report a young lady with subacute sensori-motor neuropathy as the main presenting manifestation of thyrotoxicosis. Both thyrotoxicosis and neuropathy improved on antithyroid therapy. Case Report: A 28-year-old woman presented with progressively worsening bilateral hand tremor, both lower limbs weakness and pain for two months. Her mother had past history of Graves’ disease. Examination revealed tachycardia of heart rate up to 130 bpm, a diffuse goiter of 5cm diameter, mild lower limb weakness (4/5, distal > proximal) and markedly deceased deep tendon reflexes in lower limbs (2/5). Investigations including blood counts, glucose, electrolytes, liver and renal functions, creatinine phosphokinase levels, urine analysis were normal. Imaging examinations including head CT and spinal MRI were normal. Rheumatology lab tests including ANA, antiDNA, c & pANCA, RNP Ab, Sm Ab, La Ab, Ro Ab, and Cardiolipin IgM were all negative. Blood test was negative for arsenic and lead. Thyroid function tests revealed thyrotoxicosis {TSH= 0.009 uIU/mL (normal 0.270-4.200), Free T4 =3.36 ng/dL (normal 0.93-1.70), T3 =214.9 ng/dL (normal 84.6-201.8)}. There were all positive for TSH receptor antibody was 58% (normal<14%), anti-TPO antibody was 599 IU/mL (normal<60), and thyroglobulin antibody was 112 IU/mL (normal<60). Thyroid ultrasound showed autoimmune thyroid disease. Nerve conduction studies revealed mononeuropathy, multiplex, sensori-motor, axonal type with decreased amplitude both in motor (left median, ulnar, bilateral peroneal and tibial) and sensory (bilateral sural). Antithyroid therapy with Methimazole 5mg/day combined with propranolol was initiated for 4 weeks. However, her neurologic symptoms and signs aggravated and elevated thyroid hormones levels (TSH= 0.011 uIU/mL, Free T4 =4.08 ng/dL) was noted 4 weeks later in the clinic. Follow-up nerve conduction studies revealed further markedly decrease in sensory amplitudes. Methimazole was titrated to 15mg/day then. Her neurologic symptoms and signs improved gradually associated with improved thyroid function test (TSH 0.060 uIU/mL, Free T4 =0.97 ng/dL, T3 97.3 ng/dL) and deceased TSH receptor antibody (33%) 12 weeks in the clinic. Follow-up nerve conduction studies revealed returned to nearly normal. Discussion & conclusion: The literature for study on thyrotoxic neuropathy is few and the pathogenesis remains unclear. It may be due to the direct effect of thyroid hormone, immune mediated, or due to the hypermetabolic state depleting nerve of essential substances. We presented this case with 103

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subacute polyneuropathy of two months duration and the absence of any other identifiable cause of neuropathy except thyrotoxicosis. Both of her clinical symptoms/signs and neural electrophysiological test were improved simply by antithyroid therapy with thyroid function approaching normal. Our case report suggests the clinical course of thyrotoxic neuropathy is reversible by antithyroid therapy.

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Abstract PP-06

PRIMARY SQUAMOUS CELL CARCINOMA OF THYROID: A CASE REPORT 1

HUNG-YI HUANG, 2SHIH-PING CHENG

Division of Endocrinology and Metabolism, Department of Internal Medicine, MacKay Memorial Hospital, Taiwan, R.O.C.; 2Department of General Surgery, MacKay Memorial Hospital, Taiwan, R.O.C.

Primary Squamous cell carcinoma of the thyroid is rare and usually has an aggressive clinical course. Poor response of radiation therapy, radioiodine and chemotherapy alone has been found ineffective in previously published case reports. Here we presest a 78 years old female, who complained of an enlarged left anterior neck mass with tenderness for over 6 months, with tracheal compression and underwent surgery and pathology revealed thyroid squamous cell carcinoma, and was treated with sorafanib.

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GLIMEPIRIDE-INDUCED HEMOLYTIC ANEMIA IN A GLUCOSE-6PHOSPHATE DEHYDROGENASE(G6PD) DEFICIENT PATIENT: A CASE REPORT AND LITERATURE REVIEW CHUN-TA HUANG Division of Endocrinology and Metabolism, Department of Internal Medicine, Mackay Memorial Hospital, Taipei Branch, Taiwan, R.O.C.

Introduction: Many medications have been implicated to cause hemolytic anemia in G6PDdeficient subjects. Among them, literature reports that oral anti-diabetic drug(OAD) sulfonylurea has rare but finite chance for this complication. Although U.S. Food and Drug Administration had posted a formal precaution, this potential side effect has not been well recognized. Herein, we report a case of glimepiride-induced hemolytic anemia in a G6PD-deficient man and make a literature review in search of evidence supporting this side effect. Case Description: A 42-year-old Taiwanese male presented to our clinic with polyuria, polydipsia and body weight loss. Random blood glucose was 333 mg/dl so metformin 500 mg three times daily plus vildagliptin 50 mg once daily was prescribed for newly diagnosed diabetes mellitus. He returned to clinic five days later for lab results, which showed HbA1c 12.8%, serum creatinine 0.9 mg/dL, alanine transferase 40 U/ml and hemoglobin 16 g/dL. Glimepiride 2 mg twice daily was added after he refused insulin injection. Progressive icteric skin and tea-color urine developed several days later. He was admitted for further studies, approximately 10 days after starting glimepiride. Upon admission, his hemoglobin was only 7.9 g/dL with normal platelet count and elevated reticulocyte count. His stool was hemoccult negative and blood smear discovered polychromatophilic red blood cell. Biochemistry data disclosed indirect-type hyperbilirubinemia, low haptoglobin and elevated lactate dehydrogenase level, raising the suspicion of hemolysis. Metformin and glimepiride were replaced with insulin while vildagliptin was kept for no literature has reported its linkage to hemolysis. His hemoglobin dropped further to 6.5 mg/dL on the next day and blood was transfused. Final reports were negative for both indirect and direct Coombs tests while G6PD quantitative level was very low, compatible with G6PD deficiency. After cessation of the offending drugs, his hemoglobin rose steadily to 7.7 mg/dL and he was no longer icteric. The patient was discharged on the 7th day of his admission and metformin was resumed another week later. Hemoglobin in the following month was 12.5 mg/dL without other abnormal lab data. Method: Medline database was used to search English articles published before 2015 using “hemolysis”, “hemolytic anemia” and “Glucose-6-Phosphate Dehydrogenase deficiency” as screening keywords. The eligible results were further cross-matched with “sulfonylurea” and generic names of all OAD in this category such as “tolbutamide”, “glibenclamide”, “glimepiride” etc., in 106

Abstract one by one fashion. Result: Total 13 sulfonylurea-related hemolysis case reports were identified, mostly by an immune-related mechanism. Only 3 cases were confirmed to be G6PD-deficient without other identifiable causes of their hemolysis. Of the 3 subjects, one received tolbutamide and two had glyburides. All patients recovered after drug cessation and none of them had drug rechallenged. Conclusion: Although limited data support the risk of sulfonylurea-related hemolysis in G6PDdeficient patient, one should still keep this rare but finite side effect in mind. Further studies are needed to validate this relationship.

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POORLY CONTROLLED HYPERTENSION IN A CASE WITH 17-Α HYDROXYLASE DEFICIENCY 1

YIN-HUEI CHEN, 1ZI-YUAN WANG, 2YEN-NIEN LIN, 1CHING-CHU CHEN, 1CHINGCHUNG CHANG, 1YI-CHIN HUNG 1

Division of Endocrinology and Metabolism, Department of Internal Medicine, China Medical University Hospital, Taiwan, R.O.C.; 2Division of Cardiology, Department of Internal Medicine, China Medical University Hospital, Taiwan, R.O.C.

17α-hydroxylase deficiency contributes rare entity of congenital adrenal hyperplasia and commonly presents hypertension and hypokalemia. However, the underlying mechanism of hypertension is different between 17α-hydroxylase deficiency and hyperaldosteronism. Incorrect blood pressure management may result in refractory hypertension and cardiovascular complication. Here we shared a young female presented with resistant hypertension and hypokalemia. She was complicated with left ventricular hypertrophy. After physiologic prednisolone supplement, her blood pressure was better controlled and hypokalemia was also corrected. Our case highlighted the importance of supplement in glucocorticoid pathway in care of patient with 17 alpha-hydroxylase deficiency.

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Anti-thyroid drug induces agranulocytosis is rare(0.35%).1 The common symptoms are sudden onset of fever and sore throat. However, acute appendicitis may be a rare presentation. Case report: We presented a 60-year-old female without systemic disease. She suffered from palpitation and body weight loss and final diagnosis was Graves’ disease. Carbimazole 30mg daily was initially prescribed for 35 days. After followed thyroid function became lower (3-rd TSH:<0.004 to 0.007 uIU/mL and free T4:2.67 to 1.84 ng/dL), carbimazole was reduced to 20mg daily. 23 days later, the patient suffered from fever with RLQ pain. Lab examination showed agranulocytosis(WBC 220/ uL, ANC 0/uL) which suspected carbimazole related. Emergency abdominal CT was arranged due to peritoneal sign was noted which disclosed acute appendicitis. Emergency laparoscopic appendectomy was done and acute suppurative appendicitis with focal abscess was found. We chose broad spectrum antibiotic Piperacillin/Tazobactam and then descalated to ceftazidime according to her blood culture revealed P.aeruginosa finally. G-CSF(granulocyte colony-stimulating factor) 300mcg was used for 8 days and her absolute neutrophil counts rised to more than 500/mm3 on the 9th day. After the patient was recovered from acute appendicitis and agranulocytosis, she was discharged. 10mCi I-131 ablation therapy was arranged for her in out-patient department. Hypothyroidism developed one month later and thyroxine 100mcg daily was prescribed for her. Discussion: The incidence of anti-thyroid drug induces agranulocytosis is rare (methimazole 0.35%, propylthiouracil 0.37%).1 The most common associated symptoms are sudden onset of fever and sore throat. The average time to onset is 69 days (range11-233 days, our case 58 days).2 A case series(13 patients) in Taiwan in 9 patients developed agranulocytosis under the doses of methimazole or carbimazole of 15 to 30 mg/day (mean SD: 22.78 7.12mg/day).3 Empiric broad spectrum antibiotic (including coverage for possible pseudomonas infection) should be used initially.1 For the management of hyperthyroidism which includes thionamide, radioiodine ablation, or surgery.4 Radioiodine ablation or surgery wound be considered if sever side effect of thionamide happened. For our patient, acute appendicitis is a rare presentation of carbimazole inducing agranulocytosis and we should be aware of initially. .

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CASE REPORT: CONGENITAL ADRENAL HYPERPLASIA, 21 ALPHAHYDROXYLASE DEFICIENCY, SALT-WASTING TYPE 1

CHIN-FAN CHEN, 2CHI-YU HUANG, 2YANN-JINN LEE, 2WEI-HSIN TING, CHAO-HUNG WANG, 3MING-NAN CHIEN, 1YA-CHUN HSIAO

3 1

Division of Endocrinology and Metabolism, Mackay Memorial Hospital,Hsinchu City, Taiwan, R.O.C.; Division of Pediatric Endocrinology and Metabolism, Mackay Memorial Hospital, Taipei, Taiwan, R.O.C.; 3 Division of Endocrinology and Metabolism, Mackay Memorial Hospital, Taipei, Taiwan, R.O.C. 2

6-day-old male neonate was born to a G1P1 28-year-old healthy mother with BBW of 2940 grams at GA 40+1 weeks via vaginal delivery at GYN clinic. After birth, hypospadias and bilateral undescended testis were found. Besides, neonatal jaundice occurred, then the baby was referred to our hospital. After admission , PE showed BL 50cm, BW 2.94kg, ambiguous genitalia, hyperpigmentation of scrotum and nipples, hypospadias and bilateral cryptorchidism, pallus 2.5x 1.3 cm. Newborn screen reported 17 alpha-OH-progesterone 80ng/ml. Laboratory data included total/direct bilirubin 20.8/0.9 mg/dL, hyponatremia 131mEq/dL, hyperkalemia 5.8mEq/dL. Hormone profile found low FSH and LH, cortisol 2.34μg/dL, ACTH 538.60 pg/mL, high aldosterone 72.5 ng/dL, high plasma renin activity >50 ng/mL/hr were found. Hemolytic disease of newborn(HDNB) revealed negative direct and indirect antiglobulin test (DAT, IAT), low G6PD 9.7 U/gHb (reference range 12.5-21.6). Abdominal ultrasound found uterus and adrenal gland enlargement. VCUG was remarkable. Congenital adrenal hyperplasia, suspect 21-alpha hydroxylase deficiency, salt wasting or female virilization type was impressed. Cortisone acetate 25mg 0.2 tabs BID and FludR.O.C.ortisone 1 tab were prescribed since 2014/4/15. Pediatric plasty surgeon was consulted. Genetic study evidenced CYP21A2 gene mutation. We shared the experience and special characteristics of congenital adrenal hyperplasia. The routine newborn screen is very important in neonatal metabolism and growth. The molecular analysis of genetics provides the evidence of the subtype and gender difference.

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LARGE BILATERAL ADRENAL MASS IN A 43-YEAR-OLD MAN: A CASE REPORT SHIHCHANG LO, EDY KORNELIUS, CHIEN NING HUANG Division of Endocrinology and Metabolism, Department of Internal Medicine, Chung Shan Medical University Hospital, Taichung, Taiwan

Introduction: We report a bilateral large adrenal tumor (7cm) in a 43-year-old man with the presentation of abdominal fullness, anorexia and epigastralgia. Case: A 43-year-old man presented with a 3 weeks history of progressive abdominal fullness, anorexia and epigastralgia. He had significant weight loss from 65 kilogram to 60 kilogram in 3 weeks. He visited local hospital 2 days ago, and panendoscopy discovered an ulcerative mass at stomach. He was referred to Chun-Shan medical university hospital for further investigation. Physical examination was unremarkable except epigastric tenderness. Mild hypotension (102/56 mmHg) without tachycardia was found at admission. The blood pressure was not changed after intravenous hydration and as his baseline level. Contrast abdominal CT showed large solid mass in bilateral adrenal gland with heterogenous enhancement (left side 5 x 7 cm; right side 7 x 7 cm). In addition, there were three separate gastric tumor, multiple confluent lymph nodes and several round pulmonary nodules, suggesting metastasis. Laboratory test results revealed normal blood count, serum electrolyte and serum creatine. 24-hour urinary Norepinephrine (32.5 ug/day), Epinephrine (16 ug/ day), Dopamine (400.3 ug/day) and VMA (4.1 mg/day) were within normal limit. Endocrine profile showed plasma Cortisol 14.2 ug/dl, ACTH 51.2 pg/ml, Aldosterone 43.1 pg/ml, PRA 2.22 ng/ml/hr. Panendoscopy discovered two ulcerative mass lesion at gastric body and one round mass with intact mucosa at lesser curvature, all lesions were biopsied. The pathological report were metastatic melanoma (Melan-A +, CK -, S100 +, LCA -, HMB45 +). Subsequent investigation was suggested but the patient refused and sought the secondary opinion. Conclusion: Adrenal gland is one of the common site of metastatic melanoma. Patients with melanoma adrenal metastasis have a poor prognosis. Surgical treatment should be considered only in highly selected patients.

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25 Years Old Man with Central Diabetes Insipidus 1,2

BAO-MEI WANG, 1,2,3CHING-CHIEH SU

Introduction: Diabetes insipidus can be caused by lymphocytic infundibuloneurohypophysitis, which could be detected by MRI. The natural course of the disorder is self-limited.[1] In the case report, we presented a young man with highly suspected infundibuloneurohypophysitis radiologically. Case presentation: This 25 years old man came to our endocrine outpatient department for frequent thirst and polyuria for 2 months. He noticed polydipsia(30L/day) and polyuria (10L/day) in these 2 months. He denied systemic illness, nor took any drugs such as lithium, demeclocycline. There was no glycosuria and HbA1C was 6.3%.His initial serum sodium was 141mmol/L, blood osmolarity 308 mosm/kg, urine osmolarity 108mosm/kg. Water deprivation test was arranged during admission. Serum and urine osmolarity, body weight were monitored every 1-2 hours. During water deprivation test, gradual rise of serum sodium and osmolarity was noted, as well as urine osmolarity. DDAVP nasal spray was given when urine osmolarity was stable for 3times. Rapidly increased urine osmolarity was noted. Therefore central diabetes incipidus was diagnosed and sella MRI was arranged which showed infundibuloneurohypophysitis with possible differential diagnosis of lymphocytic hypophysitis, histiocytosis,germ cell tumor, neurosarcoidosis. His serum cortisol (8AM) 21.59μg/dl, ACTH 36.1pg/ ml,testosterone 217.25ng/ml, FSH 5.49m IU/ml, LH 2.58 m IU/ml, free T4 1.54ng/ml, TSH 1.286μU/ ml HGH 0.036 ng/ml, IGF 1 124ng/ml. There was no sign or symptom of deficiency of anterior pituitary hormones. Therefore neurosurgeon was consulted for surgical intervention and transphenoidal surgery was performed. During surgery, anterior lobe specimen was sent to pathology which disclosed normal anterior lobe. However, CSF leakage was noted thereafter. Therefore, surgery was discontinued without any specimen of posterior lobe. Patient was discharged with regular minirin for DI. Discussion: Central diabetes insipidus is a chronic disorder characterized by polyuria and polydipsia due to vasopressin deficiency. The disorder may be familial, idiopathic, or secondary. Familial diabetes insipidus is characterized by autosomal dominant inheritance and, at least in some families, mutations of the vasopressin-neurophysin II genes. Secondary diabetes insipidus, the most common form of the disorder, is caused by tumors, infections, trauma, or other processes (such as histiocytosis and vascular lesions) that damage the hypothalamic-neurohypophysial system. Idiopathic diabetes insipidus, which accounts for 10 to 30 percent of cases of central diabetes insipidus, is

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Abstract characterized by selective hypofunction of the hypothalamic-neurohypophysial system. Antibodies against magnicellular neurons of the hypothalamus have been detected in some patients, leading to speculation that it is an autoimmune disorder[1] Deterioration of pituitary function was only found in patients with progressive lesions. The initial response to glucocorticoid pulse therapy was most favorable, with early failure in only 3%. However, the overall failure and recurrence rate was 41%. Recurrence rate was not related to duration of steroid administration. Side effects of steroids occurred in 63%. The surgical approach was transsphenoidal in 94%. The histological subtype was lymphocytic hypophysitis in 70% and granulomatous hypophysitis in 30%. Progression or recurrence was observed in 25% after surgical treatment.[2] Conclusion: Infundibuloneurohypophysitis is inflammatory process, was self-limited and regressed spontaneously, perhaps after the destruction of all neurons. This sequence is compatible with the autoimmune hypothesis of idiopathic diabetes insipidus.

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DIABETIC KETOACIDOSIS AS THE INITIAL PRESENTATION OF ACROMEGALY 1

YUNG-HSIN TSAI, 1,2SHYANG-RONG SHIH

Division of Endocrinology and Metabolism, Department of Internal Medicine, National Taiwan University Hospital, National Taiwan University, Taipei, Taiwan, R.O.C.; 2Department of Medicine, College of Medicine, National Taiwan University, Taipei, Taiwan, R.O.C.

Introduction: Excessive growth hormone (GH) impairs glucose metabolism by increasing insulin resistance, lipolysis and hepatic gluconeogenesis. About 19–56% of acromegaly patients developed diabetes mellitus (DM), but diabetes ketoacidosis (DKA) rarely occurred. Here we report a case of acromegaly who presented with DKA initially. Case report: A 45-year-old man with no prior medical history presented to our emergency room with dyspnea and weakness for one week. He also complained of polyuria and polydipsia in this week and weight loss for one month. Laboratory examinations showed high plasma glucose and ketoacidosis (plasma glucose: 966 mg/dL, HbA1C: 13.2%, plasma ketone: 6.1 mmol/L, arterial pH: 7.142). DKA was diagnosed and treated. Because the response to insulin therapy was poor, secondary causes of hyperglycemia were judiciously surveyed. Serum GH and insulin-like growth factor (IGF-1) were measured while there was subtle acromegaloid appearance, including mildly enlarged nose, fingers and toes. The results were abnormal (GH: 29 ng/mL, IGF-1: 468 ng/ml). Magnetic resonance imaging disclosed a pituitary macroadenoma measured 1.7 cm in diameter. Insulin requirement decreased after metformin prescribed, and further decreased to zero 4 days after trans-sphenoidal adenomectomy. GH and IGF-1 were then normalized and no anti-hyperglycemic medication was required 3 months after operation. Conclusion: We demonstrated a case of GH induced severe hyperglycemia with DKA, which was a rare initial presentation of acromegaly. Treatment of acromegaly would reach the resolution of DM. Judicious work-up for the secondary causes of hyperglycemia should be performed in all patients with difficultly controlled DM.

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SEVERE SYMPTOMATIC HYPERCALCEMIA - CHRONIC TOPHACEOUS GOUT AS THE POSSIBLE TRIGGER? 1

CHEN-TI WANG, 1, 2YUNG-CHUAN LU, 1YU-HSI KAO, 1SHU-JU KU, 1KUO-BIN TSENG 1

Division of Endocrinology and Metabolism, Department of Internal Medicine, E-DA Hospital, Kaohsiung, Taiwan; 2School of Medicine for International Students, I-Shou University College of Medicine, Kaohsiung, Taiwan

Hypercalcemia is common in clinical practice and most of the cases are due to hyperparathyroidism and malignancy. Hypercalcemia has also been associated with granulomatous diseases, which is due to enhanced extra-renal conversion of calcidiol to calcitriol by activated macrophages within the granuloma. We report a case of symptomatic hypercalcemia possibly due to chronic tophaceous gout induced granulomatous inflammation. The patient was a 52-year-old man with past history of a 30year history of gouty arthropathy with extremities deformity without any treatment. He was presented to the emergency department with altered mental status characterized by confusion, slow verbal response and lethargy. Multiple tophi had appeared on bilateral knees, elbows, hands and feet for years and he was sometimes confined to bed most of the day due to intense generalized pain. Physical examination revealed altered mental status characterized by lethargy and a Glasgow Coma Scale of 14 without focal neurological deficits. Multiple gouty tophi were obvious at inspection over bilateral wrists, elbows, metacarpophalangeal, proximal and distal interphalangeal joints, knees, ankles and the metatarsophalangeal joints. The rest of the examination was unremarkable. Laboratory tests revealed elevated uric acid (UA: 10 mg/dl; normal range 4-8.5 mg/dl), elevated calcium (Ca: 14.7 mg/dl; normal range 8.8-10.3 mg/dl), elevated phosphorous (P: 5.3 mg/dl; normal range 2.7-4.5 mg/ dl), elevated creatinine (Cr: 3.2 mg/dl; normal range 1.1-1.5 mg/dl), low intact-PTH (iPTH: 9 pg/ml; normal range 15-68.3 pg/dl), low 25-hydroxy vitamin D (25(OH) Vitamin D: 17 ng/ml; normal range 32-100 ng/ml), low hemoglobulin (Hb: 6.5 g/dl; normal range 13.5-17.5 g/dl), elevated squamous cell carcinoma (SCC: 3.5 ng/ml; normal range 0-1.5 ng/ml), normal levels of alphafetaprotein, carcinoembryonic antigen, prostatic specific antigen. It was not possible to check PTH-related peptide and 1,25-dihydroxyvitamin D in our laboratory setting. Upper gastrointestinal panendoscopy revealed gastritis and gastric ulcers. Bone marrow biopsy result showed normocellular bone marrow with small aggregates of plasma cells. Bone scan showed no evidence of bone metastasis and was consistent with gouty arthritis with multiple tophi. Gallium scan revealed moderate inflammatory pR.O.C.ess in over multiple joints, consistent with chronic gouty arthritis with multiple tophi and gout granuloma. Excisional biopsy of tophi over right thigh was arranged and pathology showed amorphous material 115

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surrounded by histiocytes and multinucleated giant cells, and result is consistent with gouty tophi. Chest computed tomography revealed a small nodule about 4 mm in size in right upper lobe. The lung nodule was too small to perform biopsy. Treatment during hospitalization included intravenous saline solution, bisphosphonates and prednisolone with a subsequent restoration of normocalcemia and improvement in renal function. Patient’s presenting symptoms were also resolved and he was discharged in stable condition. Hypercalcemia is relatively common in clinical practice and the majority of the cases are accounted for hyperparathyroidism and malignancy. Hypercalcemia has also been described in patients with various types of granulomatous disorders, with sarcoidosis being most widely evaluated. However, the association of chronic tophaceous gout with severe hypercalcemia is infrequent. The postulated mechanism is an enhanced 1α-hydroxylation of calcidiol to calcitriol by the activated mononuclear cells within the granuloma. Monosodium urate crystals in patients with chronic tophaceous gout are thought to act as the inciting antigen that leads to an intense inflammatory reaction of giant cells, macrophages and lymphocytes. It was impossible to check PTH-related peptide and 1,25-dihydroxyvitamin D in this case. In addition, the nature of the lung nodule is unknown. Hyercalcemia induced by malignancy might see an increase of PTH-related peptide. Granulomatous induced hypercalcemia may cause an increase of 1,25-dihydroxyvitamin D. Without these laboratory data, it was difficult to distinguish the actual cause of hypercalcemia in this case. Immobilization is another known cause of calcium elevations and it is likely that this was an exacerbating factor in this case. Since the patient in this case presents with multiple tophaceous gout, association with hypercalcemia should also be taken into account. It would be an interest to check calcium levels in patients with chronic tophaceous gout to determine whether hypercalcemia is a common association.

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PITUITARY STALK LESION WITH PARTIAL CENTRAL DIABETES INSIPIDUS-A CASE REPORT 1

YIN-HUEI CHEN, 1RONG-HSING CHEN, 2YEN-NIEN LIN, 1CHING-CHUNG CHANG

Central diabetes insipidus (CDI), characterized by a deficiency of arginine vasopressin, is uncommon. Causes of CDI include traumatic, infiltrative, inflammatory and neoplastic disorders of the pituitary or hypothalamus. Here in, we reported a 31 year old woman who presented with CDI due to thickened pituitary lesion. After differential diagnosis, we suspected she suffered from lymphocytic hypophysitis. With daily 20ug desmopressin nasal spray, her polyuria improved. At last, we also made literature review about pituitary stalk lesions.

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ACUTE ENLARGING GOITER AFTER INTRAVENOUS THROMBOLYSIS FOR SEVERE DEEP VEIN THROMBOSIS 1

YIN-HUEI CHEN, 1CHING-CHU CHEN, 1CHING-CHUNG CHANG, 1CHWEN-TZUEI CHANG, 2YEN-NIEN LIN, 2CHIUNG-RAY LU 1

Division of Endocrinology and Metabolism, Department of Internal Medicine, China Medical University Hospital; 2Division of Cardiology , Department of Internal Medicine, China Medical University Hospital

Nowadays, treating extensive proximal DVT had been changing with the advent of catheterdirected thrombolysis using tPA or Urokinease directly and slowly into venous thrombus via multisidehole catheter. Clinically relevant bleeding complication was less than 10%. Spontaneous hemorrhage in thyroid cysts and adenoma is common and asymptomatic. Here in, we presented a case sufferred from acute enlarging goiter after intravenous thrombolysis for severe deep vein thrombosis. Our case highlighted that closed surveillance of neck during thrombolytic therapy in patients with goiter is important.

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A NEWLY ONSET DIABETES PRESENTING WITH DKA DUE TO GAS-FORMING PYOGENIC LIVER ABSCESS COMPLICATED WITH PNEUMOPERITONEUM JUIHSIANG LI, CHI CHAO WANG Tao-Yuan General Hospital

Introduction: Pyogenic liver abscess is an infective disease of the liver, accounting for 8 to 25 cases per 100, 000 hospital admissions. Gas-forming pyogenic liver abscess (GFPLA), which accounts for 7 to 24% of pyogenic liver abscess, has a high fatality rate in spite of aggressive management (27.7 to 37.1%) (. They usually appear as an acute disease with malaise, nausea, anorexia, fever, jaudice and right upper-quadrant pain. Blood cultures are positive in 52% of the cases and the pathogens are Streptococcus species and Escherichia coli while in Taiwan the most common pathogen is Klebsiella pneumonia . Diabetic patient is immunocompromised. The disease presentation is sometimes atypical . We presented an unusual case of newly diagnosed diabetes admission with DKA due to Gas-Forming Pyogenic Liver Abscess complicated with pneumoperitoneum Case report: A 54 year-old woman had only hypertension in previous medical history. She had poor appetite and nausea recently. She ever received panendoscopy and the result showed only gastritis. Her symptoms got worsen with nausea, vomiting and general malaise for one week. She was brought to our ER for help. Findings at initial assessment at our emergent room were as follows: body temperature, 37.2∘C; blood pressure, 149/56 mmHg; regular pulse, 99 beats/min, respiratory rate , 19 times/min; weight, 53kg ; body mass index, 21 . Physical examinations indicated that the patient was clear in consciousness, had weakened appearance, anicteric sclera and smooth respiratory pattern . However, the physician did notice mild abdomen distention, but no tenderness, no rebound pain. The remarkable blood biochemistry studies showed as follows: leukocytosis with left shift (WBC=21790, seg/band/lym=69.5/17.2/3.8, Hb=13), CRP=18.63, hyperglycemia (sugar=414), A1c=16.4%, hyponatremia(Na=132), normal liver function test (AST/ALT=33/33), Vein blood gas with metabolic acidosis, (PH/pCO2/PO2/HCO3-/Be=7.098/17.3/50.6/5.2/-22.4), blood ketone body=3.7 mmol/l (reference<0.6), lactic acid=0.9 mmol/l, glycosuria and ketouria with no pyuria (glucose 4+, ketone4+, WBC=0-2/HPF), normal chest X ray image and ileus in KUB image. IV insulin and empiric anbitiotics ( cefoxin) was given. Fever (39.6°C) was noted after admission. She complained of severe abdominal pain 2 days later. We arranged chest X-ray and KUB image. Right subphrenic air was noted. Hollow organ perforation was suspected. Emergent abdominal CT was performed and an irregular lobulated lesion with air collection and rim enhancement in lateral segment of liver R/O abscess formation. The impression is pneumoperitoneum and liver abscess. Emergent

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laparotomy with abscess drainage was performed. After operation, the patient recovered well and discharged. The final blood and pus cultures showed klebsiella pneumonia infection. Discussion: The liver receives blood from both systemic and portal circulations. This increased susceptibility to infections. The three major forms of liver abscess, classified by etiology, are as follows: Pyogenic abscess, which is most often polymicrobial, accounts for 80% of hepatic abscess cases in the United States. Amebic abscess due to Entamoeba histolytica accounts for 10% of cases. Fungal abscess, most often due to Candida species, accounts for fewer than 10% of cases. The prevalence of pyogenic liver abscess in Taiwan is 17.59/100, 000. The characteristics of these patients had old age (median age 61 years), diabetes (33.3%), liver cirrhosis (10.4%), cholelithiasis(14.6%), and concomitant malignancy (13.9%). Pyogenic abscesses may be caused mainly by ascending biliary or portal tract sepsis and in lesser degree by superinfection of cysts or necrotic tissue, trauma or hematogenous dissemination. Nevertheless, in many cases (up to 25% of patients) no underlying cause is found and the disease is defined as cryptogenic. Klebsiella pneumoniae is the most common pathogen of pyogenic liver abscesses in Taiwan (2, 3, 5, 22), especially in GFPLA. This newly diagnosed diabetic patient presented with DKA and sepsis. She had no right upper abdominal pain, normal liver function test, no jaudice except fever. Until 2 days later, She suffered from severe abdominal pain because of the liver abscess rupture with peritonitis and pneuoperitoneum. She had no other abdominal lesion. Therefore, we should be highly alert to liver abscess when diabetic patient admitted due to sepsis without obvious focus on lung and urinary tract area. Liver echo and abdominal CT are helpful techniques in differential intrabdominal infection especially in liver and biliary tract infection.

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PURPOSE: Many environmental factors in high altitude differs from low altitude, such as the partial pressure of oxygen in the breathed air, temperature, humidity and solar radiation. Human physiology encounters considerable variation in high altitude during short-term exposure. Here, we present the author’s personal experience of blood sugar homeostasis in status of acute exposure to high altitude. METHOD: A 30 years old male without any systemic disease had a trip in Peru and Bolivia. Fasting sugar recored in Taiwan was all within normal limit (below 100mg/dL). The initial altitude is around 3800 meters while landing in South America, and the subject stayed above 3500 meters for five days. Portable blood glucose meters was corrected in Taiwan before travel. RESULT: The fasting finger sugar recorded in the morning were all above 100mg/dL but below 126mg/dL (112-112-110-118-101mg/dL, fasting time over 8 hours) during acute exposure to high altitude. And the post-prandial finger sugar were all within normal limit (below 140mg/dL). No acute illness except mild high mountain sickness noted during the first two days. CONCLUSION: Lowlanders acute exposure to high altitude may induce stress-related hormone and further result in high fasting sugar. However, better insulin sensitivity in status of mild hypoxia might contribute to stable post-prandial sugar. There are strong evidences that the high fasting sugar will become normal after long-term exposure to high altitude. And lots of studies reveled that lower fasting sugar, lower prevalence of diabetes and obesity in populations from high altitudes. Thus, understanding the mechanisms that regulate the lower fasting sugar in highlanders could lead to new therapeutics for impaired glucose homeostasis.

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WHAT NEXT IN PATIENTS WITH TYPE 2 DIABETES MELLITUS INADEQUATELY CONTROLLED WITH METFORMIN AND SULFONYLUREA? PIOGLITAZONE OR BASAL INSULIN?— FROM THE PERSPECTIVE OF RENAL FUNCTION CHANGE 1

YU-HUNG CHANG, 1DER-WEI HWU, 1KUN-CHEN LIN, 1DAO-MING CHANG, 2 LING-WANG AN, 3CHANG-HSUN HSIEH, 1YAU-JIUNN LEE 1

Lee’s Endocrinology Clinic; 2Beijing Ruijing Diabetes Hospital; 3Division of Endocrinology and Metabolism, Department of Internal Medicine, National Defense Medical Center, Tri-Service General Hospital, Taipei, Taiwan

Background: Despite insulin-sensitizer and insulin itself have proved their efficacy in improving glycemic control, clinical outcome may be dissimilar via their pharmacological characteristics. The aim of this study is to compare the renal function change of add on pioglitazone versus basal insulin in type 2 diabetic patients who failed of sulfonylurea and metformin regimens. Methods: Patients with type 2 diabetes mellitus (T2DM) who consecutively visited a diabetesspecific polyclinic been prescribed pioglitazone or basal insulin (i.e. detemir and glargine) for at least 2 years owing to failed of sulfonylurea and metformin control were included. Propensity score matching was used to identify well-matched groups in order to decrease potential baseline confounders. We use Cox-regression analysis to investigate the influence of pioglitazone and basal insulin to CKD progression. Results: A total of 1002 (pioglitazone: 559, detemir: 264, glargine: 179) patients were included. After propensity score matching, there were 105 patients with matchable baseline characteristics in each group. During a 3.3-year follow up, while the pioglitazone group showed a greater A1C reduction as compared with the detemir group (-0.93% vs. -0.37%, p<0.05), the pioglitazone group showed a greater body weight increase as compared with the detemir group (2.1 kg vs. 0.8 kg, p<0.05). There was no significant difference in A1C or body weight change in the group comparisons of pioglitazone vs. glargine and glargine vs. detemir. In contrast of a subtle decrease of renal function in the basal insulin groups; the pioglitazone group demonstrated a benefit in preserving renal function. In addition, the cox-regression analysis indicated that patients with detemir or glargine had higher probability of CKD progression as compared with the pioglitazone group with a hazard ratio of 2.63 (95% C.I.: 1.79~3.88) and 3.13 (95%:C.I.:2.01~4.87), respectively. Conclusion: Our study firstly showed that pioglitazone may be advantage in preserving renal function comparing basal insulin when as add on therapy for glycemic control.

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MEDULLARY THYROID CARCINOMA IN A PATIENT WITH HASHIMOTO’S THYROIDITIS 1

YU-CHUN HSUEH, 1,2TING-WEI LEE, 1,3TING-I LEE, 1CHUN-JEN CHANG, 1 YU-MEI CHIEN, 1CHI FAN 1

Division of Endocrinology and Metabolism, Taipei Medical University-Wan Fang Hospital, Taipei, Taiwan Graduate Institute of Clinical Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan 3 General Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan 2

Medullary thyroid carcinoma (MTC) is a rare form of thyroid cancer. MTC has variable cytologic patterns that makes its cytological diagnosis difficult. We report a patient with Hashimoto’s thyroiditis and elevated carcinoembryonic antigen (CEA) level that was later diagnosed as MTC. A 82 year-old man with history of hypertension and stroke who was referred to our endocrinology clinic because of right thyroid nodule. Laboratory findings were suggestive of Hashimoto’s thyroiditis in euthyroid states. A right thyroid heterogeneous nodule of about 4cm in diameter was found on thyroid sonogram. Cytological examination of the right thyroid nodule demonstrated benign follicular cells. The patient was also found to have elevated serum CEA level, thus he underwent serial of work-ups such as esophagogastroduodenoscopy, colonoscopy and CT scan of chest and abdomen which showed no evidence of malignancy. During his 4 years of follow up, he had repeated cytological studies that all showed benign follicular cells and numerous lymphocytes. However, his CEA level increased from 14.4 ng/ml to 33.4 ng/ml (reference range <5 ng/ml). Because of the progressive elevation of CEA level and increased focal uptake of right thyroid during 18F-Fluorodoexyglucose Positron Emission Tomography (FDG-PET), calcitonin was checked under the suspicion of MTC, and a markedly elevated calcitonin level 696 pg/ml (reference range 2.0-18.2 pg/ml) was found. Biochemical studies to rule out the co-existence of hyperparathyroidism and pheochromocytoma were negative. The patient underwent total thyroidectomy and neck lymph node dissection. Histopathological examination confirmed the diagnosis of MTC. Post-operatively, his CEA level lowered to 3.59 ng/ml, and calcitonin decreased to 63.5 pg/ml. Here, we highlighted the importance of considering MTC as a differential diagnosis in a patient presenting with an elevated CEA level. Thyroid nodules with increased focal uptake on FDG-PET scan are at higher risk of being malignant. Moreover, coexistence of Hashimoto’s thyroiditis might increase difficulty in cytological diagnosis of MTC.

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CLINICAL FEATURES OF METASTATIC NEUROENDOCRINE TUMOR OF THE THYROID GLAND 1

PO CHUNG CHENG, 1SHU YI WANG, 2TA-JEN WU

Division of Endocrinology and Metabolism, Department of Internal Medicine, Changhua Christian Hospital, Changhua County, Taiwan, R.O.C.

B ackground: Neuroendocrine tumor describes a heterogeneous group of neoplasms with distinctive histology and behavior. The prevalence of neuroendocrine tumor is relatively low, and these neoplasms predominantly originate from the intestine, pancreas, or the lungs. Metastatic neuroendocrine tumor of the thyroid gland is uncommon and has been described in a limited number of case reports. Methods: The clinical features of a metastatic neuroendocrine tumor of the thyroid gland are illustrated. Results: A 52-year-old man visited the emergency room of Changhua Christian Hospital due to respiratory distress for one week. Computed tomography demonstrated thyroid neoplasms with mediastinal extension and tracheal compression. Thoracoscopic biopsy revealed neuroendocrine tumor with positive staining for synaptophysin, chromogranin-A, and thyroid transcription factor-1. Conclusion: Metastatic neuroendocrine tumor of the thyroid gland is unusual and may imitate clinical features of thyroid cancer. However, metastatic thyroid neuroendocrine tumor should be distinguished from thyroid cancer because of significant differences in hormonal secretion and treatment modality. Early diagnosis and treatment of metastatic neuroendocrine tumor of the thyroid gland will likely improve the clinical outcome.

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Clinically, many diabetic patients have large vessel complications such as peripheral artery disease(PAD). It is a long and chronic course since atherosclerosis is the main etiology. If there is an atypical disease course, a rare etiology should be considered. A 41-year-old woman was diagnosed with diabetes mellitus during hospitalization of metabolic acidosis on Jul. 2014. Six months later, she was admitted to ICU due to lactate acidosis(pH 6.8, Lactate 239 ng/dL) with respiratory decompensation, and bilateral toes gangrene developed within 2 days. After 4-days intensive treatment, she was transferred out of ICU. Hyperlactatemia persisted(21.6 ng/dL) despite stable hemodynamics and oxygenation. Investigation of DM etiology showed high HbA1c(9%) with low BMI(14.7) but negative finding on T1DM antibodies, glucagon test or DM related hormone. Patient was short stature. Hearing loss was found since 20 years ago and mental slowing occurred since 1 year ago. These findings prompted us to survey mitochindrial disorder. Skeletal muscle biopsy showed red ragged fibers. Mitochondrial DNA analysis revealed A-to-G point mutation at position 3243. CT angiography did not show PAD. Autoimmune vasculitis markers were negative but tests of lupus anticoagulants were positive on Jan. 2015 and Jun. 2015. Toes gangrene may be associated with mitochondrial angiopathy or antiphospholipid syndrome. After Q10 and clopidogrel administration, serum lactate level decreased and autoamputation of toes gangrene occurred without any new ischemic lesion. The expression of mitochondrial disease is variable. Because the mitotic segregaion and heteropasmy result in the different percentage of mutated mtDNA in every cell. We reported a case of DM with toes gangrene underlying mitochondrial disease. The gangrene can be explained by mitochondrial angiopathy. But the clinical data also meets APS. It is difficult to rule out APS because the APS may cause gangrene, and the oxidant mediated injury of APS may deteriorate mtDNA mutation.

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PROGNOSTIC MARKER OF DIABETIC NEPHROPATHY: A PILOT STUDY BY METABOLOMIC APPROACH 1

CHIEN-AN CHOU, 1SZU-TAH CHEN, 2CHIA-NI LIN

Division of Endocrinology and Metabolism, Department of Internal Medicine, Chang Gung Memorial Hospital, Chang Gung University, Taoyuan, Taiwan, R.O.C.; 2Department of Laboratory Medicine, Chang Gung Memorial Hospital Linkou Branch, Taoyuan, Taiwan

Background. Diabetic nephropathy (DN) is the leading cause of ESRD, but few biomarkers of DN are available. Although biomarkers such as serum creatinine and estimated glomerular filtration rate, eGFR) are used to categorize stage of chronic kidney disease (CKD), they could not predict prognostic outcome of renal function. In order to find a more sensitive surrogate prognostic marker for CKD progression, we conducted this study by analyzing plasma metabolomics from patients with different stages of CKD. Design and methods. From September 2013 to September 2015, 49 diabetic patients with various stage of CKD were enrolled. Total of 186 metabolites including 40 acylcarnitine, 21 amino acids, 19 biogenic amines, 15 sphingomyelins and 90 glycerophospholipids were examined with UPLC/MSbased Absolute IDQ p180 kit. All metabolites were corrected between initial CKD staging and plasma concentration by Kruskal-Wallis one-way ANOVA. Events of advancing CKD stage and deterioration in eGFR and UACR in CKD stage 3 patients within 12 months’ interval were analyzed by Chi-square and Mann-Whitney U-test, respectively. Results. 12 metabolites were significantly different (5 increased and 7 decreased, P<0.05) in advanced (stage 45) CKD. By using the mean value (m45x) of each of the 12 metabolites, tryptophan (P=0.006) and t4-OH-Pro (P=0.036) were found to be associated with events of renal function deterioration in CKD stage 3 patients with their index metabolite(s) levels below m45x. However, no significant difference were noted when the numerical change of eGFR and UACR were compared (tryptophan, P=0.052; t4-OH-PRO P=0.126). Discussion. 12 metabolites (including C4, C5, Cit, Kynurenine, T4-OH-PRO, Ala, Lys, Met, Ser, Trp, Tyr, and Val) showed significant difference in advanced CKD. Tryptophan, by showing significant difference and borderline significance (P=0.006 and P=0.052) in dogmatic classification of CKD stage and continuous change in eGFR, may be regarded as a potential prognostic surrogate marker for CKD. This difference may be contributed to the limited patient number and follow up time in this study. Key words: Diabetic nephropathy, Biomarker, Metabolites

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Background: Coronary heart disease risk is higher in male in the middle-aged group and visceral obesity is a key factor related to the cardiovascular risk. Fatty infiltration of pancreas could be viewed as visceral obesity. In the previous study, the prevalence of fatty pancreas is especially higher in male aged between 40-49 years than in females in the same age population, which may explain the discrepancy of cardiovascular risk in different genders. In this article, we would like to see if there is other biochemical variant in addition to visceral obesity between different genders aged 40 to 50 years. Method: We enrolled total 307 NAFPD subjects (male: N= 219; female: N= 88) that were aged between 40 to 50 years. NAFPD was diagnosed by abdominal sonography. Biochemical parameters were compared between male and female groups by using Student’s t-test (Sigmart plot 15.0). Results: The analysis revealed no specific difference in blood glucose level (AC, PC, and HbA1C) between females and males with NAFPD aged between 40~50 years. The level of total bilirubin, direct bilirubin, ALP, and GGT were significantly higher in male group (p< 0.001). Conclusion: Male aged between 40 to 50 years with NAFPD has higher cholestasis risk than women in the same population. Further study is needed to identify if there is also significant difference of cholestasis risk in people aged 40~50 years without NAFPD, and if the discrepancy disappears in other age groups.

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A COHORT STUDY ON TEN-YEAR SURVIVAL OF SPORADIC MEDULLARY THYROID CARCINOMA WITH SOMATIC RET MUTATION: A SINGLE CENTER EXPERIENCE 1

LI-LUN CHUANG, 3,8DAW-YANG HWANG, 4KUN-BOW TSAI, 5,7HON-MAN CHAN, 6,7 FENG-YU CHIANG, 2,7PI-JUNG HSIAO 1

Division of Endocrinology and Metabolism, Kaohsiung Municipal CiJin Hospital; 2Division of Endocrinology and Metabolism, Kaohsiung Medical University Hospital; 3Division of Nephrology, Kaohsiung Medical University Hospital; 4Department of Pathology, Kaohsiung Municipal Siaogang Hospital; 5Department of Surgery, Kaohsiung Medical University Hospital; 6Department of Otolaryngology-Head and Neck Surgery; 7 School of Medicine, College of Medicine, Kaohsiung Medical University; 8Lipid Science and Aging Research Center, Kaohsiung Medical University

OBJECTIVE: Somatic RET mutations are reported in 40-50% of sporadic medullary thyroid carcinoma (sMTC) patients with prognostic significance. As it lacked somatic RET mutation reported previously for Taiwanese, we tried to assess the presence of somatic RET mutations and evaluate the potential outcome predictors for our sMTC patients. METHODS: We collected data from seven sMTC patients from 1997 to 2005 and analyzed their clinic-pathological features up to 2015. All patients were still alive to follow up for 11~18 years. Tumor DNAs were extracted to assess exons 10-11 and 13-16, and the intron-exon boundaries of the RET gene. RESULTS: Six cases (86 %) were screened positive of somatic RET gene mutations in hotspot regions, one at M918T, one at C620R and three at C634S with another two rare mutations at L629Q and V642I. CONCLUSION: Comparing the current TNM staging system, the 10-year survival outcomes for our sMTC patients was not predicted by serum calcitonin and/or CEA, surgical extent, and presence of the somatic RET gene mutations. The small cohort demonstrated a relatively good outcome of sMTC patients to survive greater than 10 years. In addition, intensive treatment with total thyroidectomy with extensive neck lymph node dissection seemed to be the critical determinant of better survival outcome for sMTC patients.

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RELATIONSHIP BETWEEN METABOLIC PARAMETERS AND TESTOSTERONE LEVEL IN MALE PATIENSTS WITH T2DM -A CROSS-SECTION STUDY IN REGIONAL HOSPITAL 1

SHIH-MING CHUANG, 1MING-NAN CHIEN, 1CHUN-CHUAN LEE, 2KAT-YIEN NGU

Division of Endocrinology and Metabolism, Department of Internal Medicine, Mackay Memorial Hospital, Taipei; 2Division of Endocrinology and Metabolism, Department of Internal Medicine, Mackay Memorial Hospital, Taitung,

Introduction: Type 2 diabetes is associated with low testosterone (LT) identified in several observation studies and systemic analyses. Besides, LT was also associated with insulin resistance and subsequent risk of developing DM. Routine serum testosterone was rare utilized and not for screeing all diabetes patients. We try to investigate what kind characteristics of LT in patients with T2DM. Methods: This cross-section study collected 80 men with T2DM who have visited our clinics. On the basis of serum testosterone level, patients were divided into two groups: LT group (serum testosterone less than 300ng/dL, n=26) and NT(normal testosterone)(testosterone more than 300ng/ dL, n=54). Body mass index(BMI), waist circumstance, glucose and lipid profiles, as well as liver and kindey function, albumin excretion rate were assessed in 3 months during testosterone measurement. Results: Our patients with diabetes have overweight in BMI and one-third of which is correspond with LT group. Compared with the NT group, LT groups were with significantly higher triglyceride(TG) level and TG/HDL ratio. Other parameters such as fasting and postpranil glucose, glycated hemoglobin, total cholesterol, liver and kindery function, AER were not significant different in both groups. Elder patients (age>65 years) have higher prevelance of LT than younger patients. There is no significant difference in lipid and glucose profile between NT and LT group in elder patients. However, younger patients have higher TG and TG/HDL ratio. Conclusions: In our investigation study, T2DM with LT was possibly associated with hyperlipidemia, especially high TG and TG/HDL ratio, in younger patients.

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HYPOGLYCEMIA AND INSULINOMA CHIH-HUANG CHIU, SHU-YI WANG Division of Endocrinology and Metabolism, Department of Internal Medicine, Changhua Christian Hospital, Changhua, Taiwan

The patient is a 36-year-old Minnan Taiwanese woman without systemic disease before. She suffered from spontaneous consciousness change for 10-20 minutes(1/3-4 months) and recover rapidly about 2-3 years. Cold sweating, hand tremor and hand tremor was noted at meantime. After pregnancy, The episode became frequently. Lab data showed HbA1c 3.7%, TSH 0.79μIU/mL, Cortisol 12.06μg/dL, C-Peptide 2.87ng/mL, when Glucose 36mg/dL, Insulin 1.81μIU/mL. we arranged 72 hr Fasting test and lab data showed Insulin: 5.21, Glucose: 43, insulin/Glucose ratio: 0.12, Cortisol (Blood, AM) 6.93. After general condition stable, Abdominal MRI was arranged and revealed Nodular tumor at pancreatic tail. Due to recurrent hypoglycemia, neuroendocrine tumor (insulinoma) is considered. Pancreatic tail tumor s/p Laparoscopic Distal Pancreatectomy on (2014-2-17). Pathology showed grade 1 neuroendocrine tumor of pancreas (PT2N0Mx). After operation, no recurrent spontaneous consciousness change was noted again.

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ACROMEGALY PRESENTING WITH NEWLY-DIAGNOSED DIABETES MELLITUS: A CASE REPORT PO-WEN YANG Department of Internal Medicine, Keelung Hospital, Ministry of Health and Welfare, Taiwan, R.O.C.

Introduction: Acromegaly is characterized by excessive production of growth hormone (GH) and insulin-like growth factor-1 (IGF-1). Pituitary GH-secretion adenoma is the major cause of acromegaly. Diabetes mellitus may develop in patients with acromegaly. Case report: A 56-year-old man presented for a second opinion for the treatment of his newly-diagnosed diabetes mellitus. He reported weight loss and polyuria for 6 months. He weighed 71 Kgs and his height was 168 cm. His blood pressure was 130/90 mmHg. He had deepened voice, enlarged hands and feet, and prominent forehead and jaw as compared to his old picture on the health insurance card. His fasting blood glucose was 300 mg/dl, and HbA1C was 12.8%. Baseline screening test for acromegaly showed elevated GH (21.850, reference range 0.003-0.971 mg/ml), and elevated IGF-1 (1015, reference range 81 - 225 ng/ ml). Skull lateral view disclosed ballooning of sella turnica. Magnetic resonance imaging of the sella revealed a homogeneously enhancing lesion involving the pituitary gland measured about 12 mm in height, suggestive of a pituitary macroadenoma. Conclusion: Acromegaly may present with newdiagnosed diabetes mellitus. A detail physical examination and review of an older photograph are clues in examining a patient suspected of having acromegaly.

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Introduction: American Diabetes Association published Standards of Medical Care in Diabetes in Diabetes Care annually. The guidelines provide health care providers with all components of diabetes care, general treatment goals, and tools to evaluate quality care. I set glycemic target for new patients with diabetes by patient/disease features in guideline first. The guidelines use metformin as first-line medication after healthy eating, weight control, increased physical activity, and diabetes education. According to drug efficacy, hypoglycemic risk, weight effect, side effects and costs, the guidelines suggest 6 kinds of medication for secondary-line choose after 3 months of monotherapy. I used homeostatic model assessment (HOMA) index as drugs adjustment tools It can evaluate severity of insulin resistance and relative beta-cell function by fasting glucose and insulin. I think HOMA index as a good tool in clinical practice. Case Report: A 67-year-old female visited Endocrinology clinic for hyperglycemia and frequent urine tract infection on 2013/11/5. In her past history, Diabetes was diagnosed on 2008 and She took sulfonylurea and metformin. HbA1c was 10.4% on 2008，10.8% on 2009. Frequent urine tract infection was noted and she visited urologic clinic regularly. She loss follow-up until 2013/6/19. She was admitted to our medical ward due to urine tract infection with fever on 2013/6/19~2013/6/24. After discharge, she took 3 kinds of oral anti-diabetic agents (sulfonylurea, metformin and D PP-4 inhibitor) for sugar control. Hypertension was diagnosed at admission and she took fixed-dose ARB/CCB for blood pressure control. Later A1c showed 8.4% on 2013/7. She visited our ER due to urine tract infection with fever on 2013/11/4. She was referred to my clinic for sugar control. I added sulfonylurea dose for it but hypoglycemia (ac sugar: 65 mg/dl on 2013/11/26) was noted. At this exam, hyperlipidemia was noted and I used statin for it. Then I decreased sulfonylurea dose and use fixed dose DPP4 inhibitor and extended release metformin. HbA1c decreased to 7.2% but elevated to 8.0% on 2014/9. I checked fasting glucose and insulin since 2015/1.High insulin resistance and insulin level was found and I decreased her sulfonylurea dose and add metformin dose.HbA1c was improving to 6.8% without hypoglycemia. 132

Abstract Discussion: According to patient/disease features in Standards of Medical Care in Diabetes in Diabetes Care，Her glucose target sets less stringent (<8%). But I used HOMA index for evaluating insulin resistance and relative beta-cell function. It can help me to improve glucose control with low hypoglycemic risk. It can be a good tool for health care providers. References: 1. Standards of Medical Care in Diabetes in Diabetes Care, 2016 2. Homeostasis model assessment: insulin resistance and beta-cell function from fasting plasma glucose and insulin concentrations in man. Diabetologia 28:412–419, 1985 3. Analysis of homeostasis model assessment-insulin resistance HOMA-IR in healthy young Chinese adults, Saudi Med J. Saudi Med J 2010 Dec; 31(12):1375-6.

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DIPEPTIDYL PEPTIDASE-4 INHIBITOR PREVENTS ARTERIAL DAMAGE THROUGH STRA6 SIGNALING BEYOND GLYCEMIC CONTROL IN HIGH FAT DIET-FED MICE 1

CHAO-HUNG CHEN, 2HSING-YI LIN, 2KUN-DER LIN, 2MEI-YUEH LEE, 2YU-LI LEE, 2 WEI-WEN HUNG, 2HE-JIUN JIANG, 2,3PI-JUNG HSIAO, 2,3SHYI-JANG SHIN 1

Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, 80708, Taiwan; 2Division of Endocrinology and Metabolism, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, 80708, Taiwan; 3Department of Internal Medicine, School of Medicine, College of Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, 80708, Taiwan

We recently found that O-GlcNAcosylation of RBP4 receptor (STRA6) with a decrease of RBP4 binding activity suppressed CRBP-1 and RARα expression and thereafter activate apoptosis and fibrosis in high-glucose cultured renal cells and in the kidneys of diabetic mice. Dipeptidyl peptidase-4 inhibitors (DPP-4i) was reported to capably ameliorate kidney fibrosis in diabetic mice. We hypothesized that DDP-4i can produce its pleiotropic action to prevent arterial damage beyond glycemic control. STRA6, CRBP1, RARα, LOX-1, caspase 3, collagen 1 and fibronectin was measured by Western blot analysis for protein and PCR for mRNA expression in the aorta in normal fat diet(NFD)-fed, high fat diet(HFD)-fed mice and sitaglitipin-treated HFD-fed mice. We aimed to investigate whether the recipR.O.C.al appearance of STRA6 cascade down-regulation and fibrosis increase in the aorta of HFD-fed mice, and whether DPP4i reverses these alterations beyond glycemic control.. The expression of STRA6, CRBP1 and RARα protein and mRNA expression remarkably decreased, while caspase 3, collagen 1, and fibronectin significantly increased in the aorta of HFD-fed mice as compared with NFD-fed mice. All these changes in the aorta of HFD-fed mice were reversed in sitaglitipin-treated HFD-fed mice. The blood glucose values in HFD-fed mice and sitaglitipintreated HFD-fed mice are not different, but are higher than NFD-fed mice. We conclude that DDP-4 inhibitor can produce its beneficial action to prevent HFD-induced fibrosis and apoptosis in arteries of HFD-treated mice by reversing the suppression of RBP 4 receptor/ CRBP-1/RARα signaling beyond its glycemic control.

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BASELINE FACTORS ASSOCIATED WITH BETTER RESPONSE TO INSULIN LISPRO LOW MIXTURE OR INSULIN GLARGINE IN DURABLE STUDY 1

THOMAS LEW, 2NAN JIA, 3ANGEL RODRIGUEZ, 4ZBIGNIEW KINDRACKI

Presenting on behalf of Eli Lilly and Company, Indianapolis, USA; 2Eli Lilly and Company, Indianapolis, USA; Eli Lilly and Company, Alcobendas, Madrid, Spain; 4Eli Lilly Poland, Warsaw, Poland

BACKGROUND: Identification of patient characteristics associated with better efficacy and safety outcomes may help clinicians in their choice of therapies. This analysis is to determine the major baseline factors associated with better efficacy and safety response for insulin lispro low mixture (LM) or insulin glargine (IG) in insulin-naïve patients with type 2 diabetes (T2D) using data from a randomized clinical trial (DURABLE Study). METHODS: Baseline covariates were used to build their nonparametric model with the efficacy and safety outcomes via the gradient boosting method (GBM). Hypothetical outcomes were calculated via this model, and treatment differences were calculated when patient was assigned to LM compared with IG. Further assessments were made to select the top baseline covariates that distinguish the greatest treatment differences. Analyzed baseline factors included baseline HbA1c, fasting blood glucose (FBG), age, body mass index (BMI), weight, duration of diabetes (DoD), and oral antidiabetic drugs use. RESULTS: This study database includes 2203 insulin-naïve patients with T2D (1102 randomized to IG and 1101 to LM). Based on the GBM, the top baseline covariates associated with the greatest treatment differences (and their relative influences) at the end of 26 weeks’ treatment are: for change in HbA1c: FBG (30.78%), age (29.66%), HbA1c (19.45%); for achieving HbA1c target of <7%: BMI (28.38%), age (23.73%), weight (23.39%); for weight change: weight (21.30%), HbA1c (19.54%), DoD (15.56%); for self-monitored FBG before morning meal: FBG (42.16%), age (17.82%), HbA1c (14.73%); for hypoglycemia frequency since last visit: FBG (50.64%), BMI (16.67%), weight (12.40%); and for hypoglycemia rate per 30-day period since last visit: FBG (56.54%), weight (12.77%), BMI (11.4%). Overall, LM shows superiority over IG in change in HbA1c and achieving HbA1c target, whereas IG shows superiority over LM in the other endpoints. CONCLUSIONS: This analysis identified baseline covariates that may predict potential treatment differences between LM and IG for the same patient. These results may help clinicians at insulin therapy initiation. DISCLOSURES: This study was supported by Eli Lilly and Company, Indianapolis, IN, USA. This is an encore of an abstract presented at the International Diabetes Federation – 23rd World Diabetes Congress, 30 November – 4 December 2015; Vancouver, Canada. 135

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ASSOCIATION BETWEEN MILD AND SEVERE HYPOGLYCEMIA IN PATIENTS WITH TYPE 2 DIABETES INITIATING INSULIN 1

THOMAS LEW, 2ADREAS FESTA, 2RAN DUAN, 2HAODA FU

Presenting on behalf of Eli Lilly and Company, Indianapolis, USA; 2Eli Lilly and Company, Indianapolis, USA

BACKGROUND: The relationship between mild (MH) and severe hypoglycemia (SH) has been quantitatively evaluated in a randomized, controlled, open-label, 2-arm, parallel study in 2008 patients with type 2 diabetes initiating insulin (insulin glargine or insulin lispro mixture 25/75). METHODS: Standard definitions were used for MH (all non-SH) and SH. A Cox regression model was employed to identify risk factors associated with incident SH. RESULTS: Average age was 56.90 (9.82) years, diabetes duration was 9.54 (6.10) years, body mass index was 31.68 (5.96) kg/m2 and HbA1c was 9.03 (1.26) %. During a treatment period of 24 weeks, 78.6% (1606/2043) of the patients experienced more than one MH, but no SH, with a mean monthly MH rate (SD) of 2.67 (2.98). Thirty-three of 2043 patients (1.6%) experienced at least one SH, with a mean monthly MH rate (SD) of 5.11 (3.98). CONCLUSIONS: Among all factors tested in the model, only the monthly MH rate (hazard ratio 1.174; confidence interval, 1.106–1.248; p<.0001) was significantly associated with SH. Stratification in high and low rates of MH showed that the risk of SH was significantly lower (p<.0002) for the low MH-rate group (MH rate ≤1.05) compared to the high rate group (MH rate ˃1.05). DISCLOSURES: This study was supported by Eli Lilly and Company, Indianapolis, IN, USA. This is an encore of an abstract presented at the American Diabetes Association – 74th Annual Scientific Sessions, 13 – 17 June 2014; San Francisco, California.

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IMPROVEMENT IN HBA1C IN PATIENTS WITH TYPE 2 DIABETES MELLITUS TREATED WITH ONCE-WEEKLY DULAGLUTIDE ACROSS BASELINE BODY MASS INDEX SUBGROUPS AT 26 OR 52 WEEKS 1

THOMAS LEW, 2LUIS ALBERTO VÁZQUE, 3ESTEBAN JÓDAR, 4 CARLOS TRESCOLI, 5CLAUDIA NICOLAY, 2JESÚS REVIRIEGO, 6 RAFFAELLA GENTILELLA 1

Presenting on behalf of Eli Lilly and Company, Indianapolis, USA; 2Eli Lilly, Alcobendas, Spain; 3Hospital Universitario Quirón, Madrid, Spain; 4Hospital Universitario de la Ribera, Alzira, Valencia, Spain; 5Lilly Deutschland GmbH, Bad Homburg, Germany; 6Lilly Diabetes, Eli Lilly Italia, Sesto Fiorentino, Italy

BACKGROUND: This post-hoc analysis investigated the efficacy of dulaglutide and active comparators across baseline body mass index (BMI) categories (BMI <30, ≥30 to <35 or ≥35kg/ m2) in patients with type 2 diabetes mellitus (T2DM) using data from the Phase 3 randomized trials AWARD-1 to -6. METHODS: Patients with T2DM received dulaglutide [1.5 mg, n=1719 (AWARD-1 to -6); 0.75 mg, n=1417 (AWARD-1 to -5)], or exenatide (n=276), insulin glargine (n=558), metformin (n=268), sitagliptin (n=315) or liraglutide (n=300), in addition to other concomitant background treatments. Analysis of covariance models (AWARD-1 to -5) or mixed-effects model for repeat measures (AWARD-6), including treatment-by-BMI subgroup interaction terms, were applied by study to estimate the effect of each treatment on HbA1c at 52 weeks (AWARD-1 to -5) or 26 weeks (AWARD-6) and to compare dulaglutide and corresponding active comparators for patients with baseline BMI <30, ≥30 to <35 or ≥35kg/m2 (intention-to-treat population). RESULTS: Baseline mean BMI in each study ranged from 31.2 to 33.6 kg/m2. HbA1c reductions from baseline according to BMI subgroup were recorded for each study. In all studies, dulaglutide 1.5 mg, dulaglutide 0.75 mg and all active comparators achieved statistically significant HbA1c reductions from baseline overall and in all BMI subgroups. No statistically significant treatment-by-BMI subgroup interactions were found for reductions in HbA1c. CONCLUSIONS: Dulaglutide (1.5 mg or 0.75 mg) is an effective treatment for patients with T2DM, regardless of baseline BMI. There was no evidence of any treatment-by-BMI subgroup interaction for HbA1c change, suggesting that baseline BMI had no effect on the relative antihyperglycemic efficacy associated with dulaglutide versus comparator antidiabetes agents. DISCLOSURES: This study was supported by Eli Lilly and Company, Indianapolis, IN, USA. This is an encore of an abstract presented at the European Association for the Study of Diabetes, 51st Annual Meeting, 14 – 18 September 2015; Stockholm, Sweden.

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COMPARISON OF EFFICACY AND SAFETY OF TWO STARTING INSULIN REGIMENS IN NON-ASIAN, ASIAN INDIAN, AND EAST ASIAN PATIENTS WITH TYPE 2 DIABETES: A POST-HOC ANALYSIS OF THE PARADIGM STUDY 1

L JI, 2KW MIN, 3J OLIVIERA, 4T LEW, 5R DUAN

OBJECTIVE: To examine differences between three racial/ethnic subgroups of insulin-naïve patients with type 2 diabetes (T2D) regarding initiation and intensification of insulin therapy with insulin lispro mix 25 (25% insulin lispro, 75% insulin lispro protamine suspension [LM25]) or insulin glargine plus insulin lispro (G+L). METHODS: This post-hoc analysis of a multi-country, randomized, open-label, active-controlled study focused on non-Asian (n=130), Asian Indian (n=106), and East Asian (n=89) patients taking oral antidiabetic medications (metformin plus sulfonylurea and/or pioglitazone) without insulin for ≥90 days who demonstrated inadequate glycemic control (HbA1c ≥7.0% [≥53 mmol/mol] and <11.0% [<97 mmol/mol]). RESULTS: HbA1c reductions were reported in all subgroups: non-Asian (LM25, 2.07%; G+L, 2.05%), Asian Indian (LM25, 1.75%; G+L, 1.60%), and East Asian (LM25, 2.03%; G+L, 1.76%); Asian Indians and East Asians recorded higher HbA1c values at endpoint than non-Asians. A higher percentage of non-Asians (LM25, 51.7%; G+L, 48.1%) achieved HbA1c <7% than Asian Indians (LM25, 43.2%; G+L, 29.2%) and East Asians (LM25, 37.5%; G+L, 36.1%), although differences were not statistically significant (p=0.12; p=0.06, respectively). Mean total daily insulin dose (U/kg) was non-Asian (LM25, 0.67; G+L, 0.61), Asian Indian (LM25, 0.91; G+L, 0.90), and East Asian (LM25, 0.53; G+L, 0.59). Ratio of mealtime to total insulin dose in G+L arm was non-Asian: 0.19±0.23, Asian Indian: 0.33±0.25, and East Asian: 0.34±0.27. Overall incidence (%) of hypoglycemia was non-Asian (LM25, 94.1; G+L, 91.8), Asian Indian (LM25, 90.4; G+L, 88.5), and East Asian (LM25, 69.8; G+L, 77.3). CONCLUSIONS: Despite greater insulin use, Asian Indians reported the least HbA1c reduction. Similar HbA1c reduction was seen in East and non-Asians, with a lower hypoglycemia rate. Greater mealtime insulin coverage was required by Asians than non-Asians. These findings highlight the importance of considering ethnicity in insulin treatment decisions for T2D patients

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Abstract AP-01

IMPROVE GLYCEMIC CONTROL IN PATIENTS WITH TYPE 2 DIABETES HARN-SHEN CHEN Division of Endocrinology and Metabolism, Department of Medicine, Taipei Veterans General Hospital, Taiwan, R.O.C.

The U.K. Prospective Diabetes Study demonstrated that good glycemic control in type 2 diabetes is associated with a reduced risk of diabetes complications. However, achieving and maintaining tight glycemic targets represent a major challenge, especially in insulin treated patients. We first demonstrated an influence of winter holiday on the glycemic control of patients who had type 2 diabetes. Then, we designed a study to investigate whether the effects of regular diabetes health education or a holiday-specific paper pamphlet before the Chinese New Year’s holidays could improve glycemic control during the winter holidays among type 2 diabetics. Self-monitoring blood glucose (SMBG) is important for patients treated with insulin to guide patients toward reaching blood glucose goal. We designed a study to improve glycemic control by a structured education package for SMBG in poorly-controlled type 2 diabetic subjects. This study reveals that a constructed education package for SMBG could improve glycemic control in type 2 diabetic subjects. We designed another pilot study to evaluate the kinetics of HbA1c levels in response to blood glucose change in type 2 diabetic patients with chronic kidney disease. We wanted the HbA1c to be able to decrease about 1.5 to 2.0% in order to see the kinetic change of HbA1c. When a patient presents with new-onset type 2 diabetes with severe hyperglycemia, the optimal treatment is aggressive insulin therapy. We designed an interventional trial to compare the effects of a further 6-month insulin therapy and oral anti-diabetic drugs on long-term glycemic control. Our main finding is that A 6-month course of insulin therapy could more effectively achieve adequate glycemic control and significant improvement of beta-cell function. A 6-month course of insulin therapy led to better 5 year glycemic control than did oral antidiabetic agent therapy in these patients. We provide health education, diabetes management, adjust insulin dose from SMBG, and encourage early insulin therapy to improve glycemic control in patients with type 2 diabetes. These serial studies not only proof some concepts but also translate these results to clinical practice.

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GENETIC DETERMINANTS OF ANTITHYROID DRUG-INDUCED AGRANULOCYTOSIS BY HUMAN LEUKOCYTE ANTIGEN GENOTYPING AND GENOME-WIDE ASSOCIATION STUDY 1,2,3,4

P-L CHEN, 1,5S-R SHIH, 6P-W WANG, 7Y-C LIN, 8C-C CHU, 7,9,10J-H LIN, 1,11S-C CHEN, 1,12,13C-C CHANG, 1,5,14T-S HUANG, 1,15K S TSAI, 1F-Y TSENG, 1C-Y WANG, 1J-Y LU, 1W-Y CHIU, 7C-C CHANG, 9Y-H CHEN, 7,16Y-T CHEN, 7C S-J FANN, 1,3,4,5 W-S YANG & 1,5T-C CHANG 1

Division of Endocrinology and Metabolism, Department of Internal Medicine, 2Department of Medical Genetics, National Taiwan University Hospital, 3Graduate Institute of Medical Genomics and Proteomics, 4Graduate Institute of Clinical Medicine, 5Department of Medicine, College of Medicine, National Taiwan University, 6 Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, 7Institute of Biomedical Sciences, Academia Sinica, 8Immunogenetics Laboratory, Medical Research Department, Mackay Memorial Hospital, 9School of Pharmacy, National Taiwan University, 10Research Center for Applied Sciences, Academia Sinica, 11Department of Internal Medicine, New Taipei City Hospital, 12 Department of Internal Medicine, China Medical University Hospital, 13Department of Internal Medicine, China Medical University, 14Department of Social Medicine, 15Department of Laboratory Medicine, College of Medicine, National Taiwan University, 16Department of Pediatrics, Duke University Medical Center, Durham, North Carolina 27708, United States of America

Graves’ disease is the leading cause of hyperthyroidism affecting 1.0-1.6% of the population. Anti-thyroid drugs are the treatment cornerstone, but may cause life-threatening agranulocytosis. Here we conduct a two-stage association study on two separate subject sets (in total 42 agranulocytosis cases and 1,208 Graves’ disease controls), using direct human leukocyte antigen genotyping and SNP-based genome-wide association study. We demonstrate HLA-B*38:02 (Armitage trend Pcombined = 6.75 × 10-32) and HLA-DRB1*08:03 (Pcombined = 1.83 × 10-9) as independent susceptibility loci. The genome-wide association study identifies the same signals. Estimated odds ratios for these two loci comparing effective allele carriers to non-carriers are 21.48 (95% confidence interval = 11.13-41.48) and 6.13 (95% confidence interval = 3.28-11.46), respectively. Carrying both HLA-B*38:02 and HLADRB1*08:03 increases odds ratio to 48.41 (Pcombined = 3.32 × 10-21, 95% confidence interval = 21.66108.22). Our results could be useful for anti-thyroid-induced agranulocytosis and potentially for agranulocytosis caused by other chemicals.

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Glucose Variability and beta- Cell Response by GLP-1 Analogue added-on CSII for Patients with Poorly Controlled Type 2 Diabetes 1,2

C-H LIN, 1S-H HSIEH, 1J-H SUN, 3J-S TSAI, 1Y-Y HUANG

Introduction: The purpose of this study was to test the effects of twice-daily exenatide injections added on continuous subcutaneous insulin infusion in patients with poorly controlled type 2 diabetes (T2DM). Methods: Patients with poorly controlled (A1C 8-12%) T2DM were randomized to receive a 6-day course of continuous subcutaneous insulin infusion (CSII) during hospitalization. After optimization of blood glucose in the first 3 days, patients were randomized to receive CSII combined with injections of exenatide for another 3 days or placebo. Biomarkers and 75 g oral glucose tolerance test (OGTT) were performed at baseline (day 0) and endpoint (day 7). Results: A total of 51 patients (30 in exenatide and 21 in placebo groups) with mean A1C 11 % were studied. At endpoint, the mean glucose was 143.93±4.15 and 153.36±5.13 mg/dl in exenatide and placebo groups, respectively (p = 0.167). There was no difference in daily insulin dose but a significant higher standard deviation of plasma glucose (SDPG) was found in the exenatide group (50.51±2.43 vs. 41.49±3.00 mg/dl, p = 0.027). The improvement of incremental area under the curve (AUC) of glucose and insulinogenic index (Insulin0–peak/ Glucose0–peak) was prominent in the exenatide group (p < 0.01). The adiponectin level was significantly increased with exenatide added on (0.39 ± 0.32 vs. -1.62 ± 0.97 μg/mL, in exenatide and placebo groups, respectively, p = 0.045). Conclusions: The add-on of GLP-1 analogue to CSII increased glucose variability and the β cell response in patients with poorly controlled T2DM. Keywords: GLP-1 analogue, CSII, type 2 diabetes

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AP-04

THE ASSOCIATION BETWEEN BODY MASS INDEX AND ALL-CAUSE MORTALITY IN PATIENTS WITH TYPE 2 DIABETES MELLITUS: A 5.5-YEAR PRPPECTIVE ANALYSIS 1

J-F KUO, 2Y-T HSIEH, 1I-C MAO, 1S-D LIN, 1S-T TU, 1,3M-C HSIEH

Department of Internal Medicine, Division of Endocrinology and Metabolism, Changhua Christian Hospital, Changhua, Taiwan, R.O.C.; 2Department of Ophthalmology, National Taiwan University Hospital, Taipei, Taiwan, R.O.C.; 3Graduate Institute of Integrated Medicine, China Medical University, Taichung, Taiwan

OBJECTIVE: Abundances of study in different population have noted that obese cardiovascular disease (CVD) patients have a better prognosis than leaner patients, which refer to the phenomenon of obesity paradox. However, data on the association between body mass index (BMI) and mortality among Asian patients are limited, especially in patients with type 2 diabetes mellitus (T2DM). We investigate the association between BMI and all-cause mortality in Taiwanese patients with T2DM to define the optimal body weight for health. METHOD: We conducted a longitudinal cohort study of 2161 T2DM patients with a mean follow-up period of 66.7±7.5 months. Using Cox regression models, BMI was related to the risk of allcause mortality after adjusting all confounding factors. RESULT: A U-shaped association between BMI and all-cause mortality was observed among all participants. Those with BMIs <22.5 kg/m2 had a significantly elevated all-cause mortality as compared with those with BMIs 22.5 to 25.0 kg/m2, (BMIs 17.5–20.0 kg/m2: hazard ratio 1.989, p<0.001; BMIs 20.0–22.5 kg/m2: hazard ratio 1.286, p=0.02), as did those with BMIs >30.0 kg/m2 (BMIs 30.0–32.5 kg/m2: hazard ratio 1.670, p<0.001; BMIs 32.5–35.0 kg/m2: hazard ratio, 2.632, p<0.001). This U-shaped association remained when we examined the data by sex, age, smoking, and kidney function. CONCLUSION: Our study found a U-shaped relationship between all-cause mortality and BMI in Asian patients with T2DM, irrespective of age, sex, smoking, and kidney function. BMI <30 kg/m2 should be regarded as a potentially important target in the weight management of T2DM.

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Abstract AP-05

Genetic Polymorphisms of PCSK2 are Associated with Glucose Homeostasis and Progression to Type 2 Diabetes in a Chinese Population. 1

TJ CHANG, 2YF CHIU, 3WH SHEU, 4KC SHIH, 5,6CM HWU, 7 QUERTERMOUS T, 8YS JOU, 1SS KUO , 1,9 YC CHANG, 1,10 LM CHUANG 1

Department of Internal Medicine, National Taiwan University Hospital, Taipei 10002, Taiwan; 2Department of Bioinformatics and Biostatistics, National Health Research Institutes, Zhunan Town, Miaoli County 35053, Taiwan; 3Department of Internal Medicine, Taichung Veterans General Hospital, Taichung 40705, Taiwan; 4 Division of Endocrinology and Metabolism, Taipei Veterans General Hospital, Taipei 11217, Taiwan; 5Section of General Medicine, Department of Medicine, Taipei Veterans General Hospital, Taipei 11127, Taiwan; 6 Faculty of Medicine, National Yang-Ming University School of Medicine, Taipei 11221, Taiwan; 7Division of Cardiovascular Medicine, Falk Cardiovascular Research Building, Stanford University School of Medicine, Stanford, CA 94305, USA; 8Institute of Biomedical Sciences, Academia Sinica, Taipei 11529, Taiwan; 9Graduate Institute of Medical Genomics and Proteomics, National Taiwan University College of Medicine, Taipei 10055 Taiwan; 10Institute of Epidemiology and Preventive Medicine, College of Public Health, National Taiwan University, Taipei 10055, Taiwan.

Proprotein convertase subtilisin/kexin type 2 (PCSK2) is a prohormone processing enzyme involved in insulin and glucagon biosynthesis. We previously found the genetic polymorphism of PCSK2 on chromosome 20 was responsible for the linkage peak of several glucose homeostasis parameters. The aim of this study is to investigate the association between genetic variants of PCSK2 and glucose homeostasis parameters and incident diabetes. Total 1142 Chinese participants were recruited from the Stanford Asia-Pacific Program for Hypertension and Insulin Resistance (SAPPHIRe) family study, and 759 participants were followed up for 5 years. Ten SNPs of the PCSK2 gene were genotyped. Variants of rs6044695 and rs2284912 were associated with fasting plasma glucose, and variants of rs2269023 were associated with fasting plasma glucose and 1-hour plasma glucose during OGTT. Haplotypes of rs4814605/rs1078199 were associated with fasting plasma insulin levels and HOMA-IR. Haplotypes of rs890609/rs2269023 were also associated with fasting plasma glucose, fasting insulin and HOMA-IR. In the longitudinal study, we found individuals carrying TA/AA genotypes of rs6044695 or TC/CC genotypes of rs2284912 had lower incidence of diabetes during the 5-year follow-up. Our results indicated that PCSK2 gene polymorphisms are associated with pleiotropic effects on various traits of glucose homeostasis and incident diabetes.

143

The

th Annual Meeting of March 19-20, 2016 The Endocrine Society and The Diabetes Association of the R.O.C. (Taiwan)

AP-06

CLINICAL CHARACTERISTICS AND RISK FACTOR ANALYSIS FOR LOWER-EXTREMITY AMPUTATIONS IN DIABETIC PATIENTS WITH FOOT ULCER COMPLICATED BY NECROTIZ FASCIITIS 1

I-WEN CHEN, 1HUI-MEI YANG, 2CHENG-HSUN CHIU, 3 JIUN-TING YEH, 1CHUNG-HUEI HUANG, 1YU-YAO HUANG 1

Division of Endocrinology and Metabolism, Department of Internal Medicine, Chang Gung Memorial Hospital, Chang Gung University, Taiwan; 2Molecular Infectious Disease Research Center, Division of Pediatric Infectious Diseases, Department of Pediatrics, Chang Gung Memorial Hospital, Chang Gung University, Taiwan; 3Division of Trauma Plastic Surgery, Department of Plastic and Reconstructive Surgery, Chang Gung Memorial Hospital, Chang Gung University, Taiwan.

Patients with diabetes are at a higher risk of having diabetic foot ulcers (DFU) or necrotizing fasciitis (NF). The present study aims to examine the clinical characteristics and associated risk factors for lower-extremity amputation (LEA) in patients with DFU complicated by NF. We retrospectively reviewed patients treated at a major diabetes center in Taiwan between 2009 and 2014. Of the 2,265 cases 110 had lower-extremity NF. Limb preservation outcomes were classified as major LEA, minor LEA or limb-preserved. Clinical characteristics, laboratory data, and bacterial culture results were collected for analysis. Of the 110 patients with NF, 100 had concomitant diabetic foot ulcers (NF with DFU) and the remaining 10 had no DFU (NF without DFU). None of the NF patients without DFU died nor had their leg amputated. Two NF patients with DFU died of complications. The amputation rate in the surviving 98 NF patients with DFU was 72.4% (46.9% minor LEA and 25.5% major LEA). Seventy percent of the NF patients without DFU had monomicrobial infections (60% with Streptococcus species), and 81.4% NF patients with DFU had polymicrobial infections. Anaerobic organisms were identified in 66% of the NF patients with DFU. Multinomial logistic regression analysis revealed an association between high-grade Wagner wound classification (Wagner 4 and Wagner 5) and LEA (adjusted odds ratio [aOR]= 21.856, 95% confidence interval [95% CI] =1.625–203.947, P = 0.02 and aOR= 20.094, 95% CI = 1.968–205.216, P = 0.01 for major and minor LEA, respectively) for NF patients with DFU. In addition, a lower serum albumin level was associated with major LEA (OR = 0.066, P = 0.002). In summary, once diabetic foot ulcers were complicated by NF, the risk of amputation increased. Empirical treatment for NF patients with DFU should cover polymicrobial infections, including anaerobic organisms. The high-grade wound classification and low serum albumin level were associated with LEA.

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105年會論文摘要集

Articles inside

Poster Presentation

2016 Award

Oral Presentation-2

Iodine Nutrition in Taiwan

Gender and Medicine

Thyroid Symposium

Adrenal Symposium

Bone Metabolism & Osteoporosis Symposium

The International Voice

ESROC-KES Joint Symposium

Board of Directors

2016 Taiwan Diabetes Prevention, Treatment and Prospect of a New Realm

New Developments in Cushing’s Syndrome