Thyroid Symposium

S4-1 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, Ministry of Health, Singapore Member 2014-2016 Endocrine & Metabolic Society of Singapore President 2013-2014 Chapter of Endocrinology, Academy of Medicine, Singapore Chairman 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

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.

S4-2 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 Chang Gung Memorial Hospital, Taipei, Taiwan Residency in Internal Medicine 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.Huang 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.

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 131I 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.

S4-3 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.

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.Khosroshahi 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