PE：Poster Presentation-Endocrine (1-28

PE01 ECTOPIC ADRENOCORTICAL CARCINOMA IN THE OVARY: A CASE REPORT

1WEN-HSUAN TSAI, 2TZE-CHIEN CHEN, 3SHUEN-HAN DAI, 1YI-HONG ZENG

1Division of Endocrinology and Metabolism, Department of Internal Medicine, Mackay Memorial Hospital, Taipei, Taiwan (ROC); 2 Department of Obstetrics and Gynecology, Mackay Memorial Hospital, Taipei, Taiwan (ROC); 3 Department of Pathology, Mackay Memorial Hospital, Taipei, Taiwan (ROC)

Adrenocortical carcinoma (ACC) is a rare malignancy with an incidence of 0.7–2.0 cases/ million habitants/year. Ectopic adrenal adenomas are uncommon and ectopic ACCs are rarely seen. We presented a 59-year-old woman who suffered from abdominal fullness for 6 months and increased abdominal circumstance. A huge pelvic tumor was noted. She received debulking operation. Initial diagnosis was ovarian neuroendocrine carcinoma with omentum, lymph nodes, lung and peritoneum metastasis. Pathology report revealed local tumor necrosis and prominent lympho-vascular invasion. The Ki-67 proliferation labeling index is very high > 50%. Immunohistochemically, tumor cells are focally positive for CD56, synaptophysin but also focally positive for calretinin. She received 3 cycles of etoposide, cisplatin and bevacizumab. 2 months later, pathologist confirmed diagnosis of ectopic ACC by positivity for synaptophysin, alpha-inhibin, TFE-3, calretinin (focal), and CD56 (focal), and high Ki-67-labeling proliferating index (> 80%). Non-functioning tumor was diagnosed according to hormone profile. She received mitotane 6 months after operation but died of cachexia 3 months later. There was limited knowledge of the incidence and prognosis of ectopic ACC. Diagnosing ACC from ectopic organ can be tricky and comprehensive IHC may shed light on the correct diagnosis.

PE02 WEE1 INHIBITION BY ADVOSERTIB FOR ANAPLASTIC THYROID CANCER THERAPY

123YU-LING LU, 123SHU-FU LIN,

4YU-TUNG HUANG, 5TING-CHAO CHOU,

6RICHARD J. WONG

1Department of Internal Medicine, New Taipei Municipal TuCheng Hospital, New Taipei City, Taiwan;

2Department of Internal Medicine, Chang Gung Memorial Hospital, Taoyuan, Taiwan; 3Chang Gung University,

Taoyuan, Taiwan; 4

Center for Big Data Analytics and Statistics, Chang Gung Memorial Hospital, Taoyuan, Taiwan; 5Laboratory of Preclinical Pharmacology Core, Memorial Sloan-Kettering Cancer Center, New York, NY, USA; 6Department of Surgery, Memorial Sloan-Kettering Cancer Center, New York, NY, USA

Background: Wee1 is a kinase that regulates the G2/M progression by inhibition of CDK1, which is critical for ensuring DNA damage repair before initiation of mitotic entry. Targeting Wee1 may be a potential strategy in the treatment of anaplastic thyroid cancer, a rare but lethal disease.

Methods: The therapeutic efficacy of Adavosertib, a Wee1 inhibitor for treatment of ATC was evaluated in vitro and in vivo. The expression of cleaved PARP was assessed using Western blot. Cell cycle distribution was measured by flow cytometry and immunofluorescence microscopy. Apoptosis and caspase-3 activity were evaluated by flow cytometry and fluorometric assay. Mice bearing flank ATC were treated with either adavosertib, dabrafenib plus trametinib, or combination of adavosertib with dabrafenib plus trametinib.

Results: Adavosertib inhibited cell growth in three anaplastic thyroid cancer cell lines in a dose-dependent manner. Cell cycle analysis revealed cells were accumulated in the G2/M phase. Adavosertib induced caspase-3 activity and led to apoptosis. Adavosertib monotherapy did not significantly retard the growth of anaplastic thyroid cancer tumors in two xenograft models. However, the combination of adavosertib with dabrafenib plus trametinib significantly inhibited tumor growth compared with placebo treatment in two anaplastic thyroid cancer xenograft models with BRAFV600E mutation.

Conclusions: Our findings suggest adavosertib holds the promise for the treatment of patients with anaplastic thyroid cancer.

PE03 LOW DOSE OF LENVATINIB TREATMENT FOR PATIENTS OF RADIOIODINE-REFRACTORY DIFFERENTIATED THYROID CARCINOMA: A REAL-WORLD EXPERIENCE

1HE-JIUN JIANG,

2YEN-HSIANG CHANGE, 3YEN-HAO CHEN, 3YEN-YANG CHEN,

2PEI-WEN WANG,

1PI-JUNG HSIAO

1Division of Endocrinology and Metabolism, Department of Internal Medicine, E-DA Dachang Hospital;

2

Department of Nuclear Medicine, Kaohsiung Chang Gung Memorial Hospital; 3Department of HematologyOncology, Kaohsiung Chang-Gung Memorial Hospital

Background: Lenvatinib treatment of 24 mg/day for radioiodine-refractory differentiated thyroid carcinoma (RRDTC) patients was almost intolerable, with high rates of dose reduction, interruption and discontinuation. Balancing treatment safety, disease risks and appropriate dose remains challenging. A real-world experience of low dose of lenvatinib treatment was assessed from two medical centers of South Taiwan.

Methods: A total of 65 RRDTC patients treated with lenvatinib were retrospectively reviewed from Oct. 2015 to Mar. 2020. The median follow-up period was 48 months. Drug tolerability, treatment efficacy and clinical outcomes were analyzed.

Results: Lenvatinib was initiated and maintained with a median dose of 10 mg/day at 10 mg/ day in the first 3 months. The disease control rate reached 89.2%, including 24.6% partial response and 64.6% stable disease. Disease progression occurred in 10.8% of patients and increased to 40.0% at the end of follow-up. Eventually, the low dose treatment achieved a median progression-free survival (PFS) of 26.1 month (95% CI: 17.1-NA) with overall survival (OS) not reached yet (24.1~NA). Overall, the 48-month PFS rate was 35.6% (95% CI: 18.5-68.4) and 48-month OS was 54.3% (95% CI: 41.2-71.7). The dose was tolerable with a dose reduction rate of 44.6%, dose interruption rate of 40.0% and fewer high-graded adverse events. The drug discontinuation rate was only 3.1%. Low dose lenvatinib treatment appeared beneficial for patients with less bone metastasis or structural progression.

Conclusions: Assessing treatment intensity, safety and efficacy, low dose lenvatinib treatment was well tolerated by patients with RRDTC and the therapy displayed acceptable drug efficacy and competitive outcomes.

PE04 DETERMINATION OF IODINE CONTENT IN MILK AND EGGS

1FAN-FEN WANG, 2CHYI-HUEY BAI, 3KAM-TSUN TANG, 4YI-LIN LIU,

4CHEN-CHANG YANG,

3CHUN-JUI HUANG,

1SHEAU-FANG PAN

1Division of Endocrinology and Metabolism, Department of Medicine, Yangming Branch, Taipei City Hospital, Taipei, Taiwan; 2Department of Public Health, College of Public Health, Taipei Medical University, Taipei, Taiwan; 3Division of Endocrinology and Metabolism, Taipei Veterans General Hospital, Taipei, Taiwan;

4Department of Clinical Toxicology & Occupational Medicine, Taipei Veterans General Hospital, Taipei, Taiwan

Background: Iodine is essential for the production of thyroid hormones and is acquired through the diet. Dairy products and eggs are primary source of iodine in many countries. However, a survey of iodine content of dairy products and eggs had not been conducted in Taiwan.

Methods: The current study is a sub-study of the Nutrition Survey of Pregnant Women in Taiwan 2017-2019, evaluating dietary iodine sources. Iodine levels of 10 brands of liquid milk, 7 brands of milk made from milk powder, and 10 brands of yogurt were measured by inductively coupled plasma mass spectrometry. Iodine content of the yolk of boiled eggs was measured by thermal cycler digestion microplate method.

Results: All liquid milk samples had at least 43.8 μg iodine/250ml, ranging from 43.8-68.2 μg (median: 49.4 μg). The median iodine levels in milk made from milk powder was lower (11.8 μg iodine/250ml, range: 8.6-80.5 μg). The median iodine concentration of yogurt was 15.2 μg iodine/250ml, but the iodine level of one brand of yogurt reached to 152.7 μg/250ml. The 6 brands of eggs contained a median 19 μg/yolk of iodine (range 12.2-40.5 μg).

Conclusions: Iodine is contained in dietary food in Taiwan as in many other countries, but in varying concentrations, especially in yogurt. However, iodine content is not reported on most food labels. We suggest the iodine content of liquid milk, milk powders, and yogurt should be included in the ingredient and nutrient lists on package labels.

PE05 POSTERIOR REVERSIBLE ENCEPHALOPATHY SYNDROME INDUCED BY ABIRATERONE IN A PATIENT WITH METASTATIC PROSTATE CANCER: A CASE REPORT

1KUAN-YU LIN, 2HAO-CHIA HSU, 1CHUN HSIEN LIN, 3KUAN-HUA CHEN,

2JEN-JEN SU, 1SHYANG-RONG SHIH

1 Division of Endocrine and Metabolism National Taiwan University Hospital; 2 Department of Neurology, National Taiwan University Hospital; 3 Division of Endocrine and Metabolism E-Da Hospital

Background: The selective CYP17 inhibitor, abiraterone, blocks androgen biosynthesis, and is approved for treating metastatic prostate cancer in combination with prednisolone. Treatment with abiraterone alone is associated with symptoms and signs of mineralocorticoid excess, including high blood pressure and hypokalemia.

Posterior reversible encephalopathy syndrome (PRES) is an acute neurotoxic syndrome presented with reversible subcortical vasogenic brain edema, and usually resulted from rapid blood pressure ascension. Here, we report the first case of abiraterone-induced refractory hypertension and PRES.

Case presentation: An 82-year-old man, diagnosed with metastatic prostate cancer in January 2020, underwent palliative transurethral prostatectomy in May 2020. Due to biochemical progression under androgen deprivation therapy with leuprolide and bicalutamide, abiraterone acetate was initiated alone in June 2020. The patient developed severe headaches and hypertension one month later and was sent to the emergency department owing to deteriorating consciousness. Emergent brain magnetic resonance imaging (MRI) revealed bilateral posterior cerebral focal edema, and initial laboratory data revealed hypokalemia. He was admitted to the intensive care unit, but his symptoms responded poorly to multiple antihypertensive agents. Assessment of secondary hypertension revealed elevated serum levels of adrenocorticotropic hormone (ACTH) and aldosterone, and reduced levels of cortisol, progesterone and testosterone. Under the impression of medication related secondary hypertension, abiraterone was discontinued owing to abiraterone-induced adrenal insufficiency and mineralocorticoid excess. Glucocorticoid supplementation with prednisolone 7.5 milligrams daily was initiated. His symptoms soon improved, and the anti-hypertensives and potassium supplementation were discontinued. His consiousness was clear and oriented during the remaining admission period.

Conclusions: In conclusion, abiraterone induces secondary hypertension, and should be combined with corticosteroids for treatment. If not, adequate monitoring of blood pressure and electrolytes are necessary.

PE06 FOLLICULAR THYROID CARCINOMA PRESENTING AS A GROWING SCALP MASS: A CASE REPORT

1TSUNG-HUI WU, 1FANG-YU CHEN,

1HUI-LING LIN, 2CHUN-FENG WU,

1,2TANG-YI LIAO, 1,3,4CHIN-SUNG KUO

1Division of Endocrinology and Metabolism, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan; 2Division of Endocrinology and Metabolism, Department of Internal Medicine, Dalin Tzu Chi Hospital, Chiayi, Taiwan; 3Cardiovascular Research Center, National Yang-Ming University, Taipei, Taiwan; 4Institute of Clinical Medicine, National Yang-Ming University, Taipei, Taiwan

Background: Metastasis of follicular thyroid carcinoma to the skull is rare, and the prognosis is poor in these patients. Total thyroidectomy and removal of metastatic lesions remain the first treatment, and radioactive iodine therapy should be performed postoperatively. Tyrosine kinase inhibitor therapy could be considered in patients with radioactive iodine-refractory metastatic follicular thyroid carcinoma.

Methods: We report a case of follicular thyroid carcinoma with skull metastasis as the presenting symptom.

Results: The 46-year-old female patient presented to our endocrine clinic due to a growing bulging mass at posterior scalp for 1 year. She underwent right thyroid lobectomy 10 years ago and left thyroid lobectomy 3 years ago for multinodular goiter. Thyroid nodules were diagnosed as follicular adenomas based on the second operation. However, histopathological examination of the biopsy taken from the scalp lesion showed metastatic follicular thyroid carcinoma. The serial image studies revealed prominent tumor mass at left thyroid fossa with cervical lymphadenopathy and distant metastases to brain, skull, nasal tip, bilateral lungs, liver, right kidney with invasion to right renal vein and inferior vena cava, left adrenal gland, and bone. She received craniotomy, total thyroidectomy with lymph node dissection, and right radical nephrectomy combined with left adrenalectomy, inferior vena cava thrombectomy, and partial hepatectomy sequentially. She had radioactive iodine therapies for 2 times after surgeries. As metastatic tumors became radioactive iodine-refractory, she received lenvatinib to control the metastatic disease.

Conclusions: The possibility of skull metastasis from follicular thyroid carcinoma should be considered in patients with metastatic skull tumors.

PE07 A NOVEL MUTATION OF THE AVPR2 GENE CAUSING NEPHROGENIC DIABETES INSIPIDUS: A CASE REPORT AND REVIEW OF LITERATURE

1YU-LIN YANG, 1YI-HONG ZENG, 2PEI-CHEN WU, 1CHUN-CHUAN LEE

1Division of Endocrinology and Metabolism, Department of Internal Medicine, MacKay Memorial Hospital, Taipei 10449, Taiwan, R.O.C.; 2Division of Nephrology, Department of Internal Medicine, MacKay Memorial Hospital, Taipei 10449, Taiwan, R.O.C.

Background: Congenital nephrogenic diabetes insipidus (cNDI) is a rare disease characterized by a malfunctioning renal response to the antidiuretic hormone arginine vasopressin (AVP). Approximately 90% of all patients with cNDI have X-linked inherited disease caused by variants in the arginine vasopressin receptor 2 (AVPR2) gene. Our objective is to report a small deletion in the AVPR2 gene causing cNDI in a 29-year-old man, presenting with chronic polyuria, polydipsia, recurrent urinary tract infection, bilateral severe hydroureter, bilateral pelviectasis, detrusor muscle areflexia, and an atonic bladder.

Case description: The patient was diagnosed with NDI based on the clinical phenotype, the water deprivation test and the inadequate response to 1-desamino-8-Darginine vasopressin (DDAVP) administration. Sequencing analysis of the AVPR2 gene revealed a novel mutation of c.328delG, p.Ala110fs and his mother was also the carrier of AVPR2 gene c.328delG.

PE08 THE INCREASING RISK OF PAPILLARY THYROID MICROCARCINOMA: A SINGLE-CENTER EXPERIENCE

LI-CHING LI, KORNELIUS EDY, SHIH-CHANG LO, CHIEN-NING HUANG, YI-SUN YANG

Division of Endocrinology and Metabolism, Department of Internal Medicine, Chung Shan Medical University Hospital, Taichung, Taiwan, R.O.C.

Background: Thyroid cancer incidence has surged globally, the most common type is Papillary thyroid carcinoma (PTC), accounting for 70-90%. Papillary thyroid micro-carcinoma (PTMC) was defined by PTC tumor size with less than 1 cm in diameter. This study aimed to evaluate the prevalence of PTMC in Chung-Shan Medical University Hospital (CSMUH).

Methods and Results: Between 2016 and 2019, we retrospectively analysed 287 thyroid cancer patients in CSMUH. We found that PTMC patients were primarily diagnosed incidentally after a thyroid operation. Only eight cases were discovered by ultrasound-guided fine-needle aspiration cytology before surgery. 225 patients (78.3%) of all thyroid cancers were diagnosed as PTC. Among PTC patients, 75 patients (33.3%) were diagnosed as PTMC and 32 patients (14.2%) had combined PTMC and PTC tumor size with more than 1 cm in diameter. The Prevalence of PTC among thyroid cancer patients in CSMUH increased from 70.4% in 2016 to 80.3% in 2019, while that of PTMC also increased from 29.5% in 2016 to 39.2% in 2019. Patients with papillary subtype contained a higher proportion of females (75%). In the age-specific prevalence of PTC, males (peak 60-69 years) were generally older than the females (peak 40-49 years). In contrast, PTMC cases were mostly diagnosed at a younger age in males (peak 40-49 years) than females (peak 50-59 years).

Conclusions: PTMC stands the common subtype of PTC in thyroid malignancy that increasing numbers in recent years. In prevalence, although females were found to be younger in PTC, males were younger than females in PTMC.

PE09 SEVERE OSTEOPOROSIS WITH HYPOPHOSPHATEMIA PRESENTATION: A CASE REPORT

CHING-MEI HSU, KORNELIUS EDY, SHIH-CHANG LO, CHIEN-NING HUANG, YI-SUN YANG

Division of Endocrinology and Metabolism, Department of Internal Medicine, Chung Shan Medical University Hospital, Taichung, Taiwan, ROC.

Background: Hypophosphatemia appears most often in acutely or critically ill individuals. In order to delineate among the causes of hypophosphatemia in the setting of metabolic bone diseases, it is important to obtain a thorough history, physical examination and laboratory analysis.

Methods: We reported a case of hypophosphatemia with laboratory data and imaging studies including X-ray and lumbar spine magnetic resonance imaging.

Results: A 65-year-old male presented for evaluation of fragility fracture in the setting of hypophosphatemia. At age of 60, he was given a diagnosis of cervical radiculopathy, severe osteoporosis, Parkinsonism and was placed on therapy of Madopar and analgesic agents. In the past five years, he had worsened decrease in body height at a rate of 1 centimeter per every three months. He was a vegetarian for 27 year and heavy smoker. On physical examination, the patient had a height of 141cm and a weight of 33kg. Laboratory data showed low serum phosphorus (1.6mg/dl), mild low serum creatinine(0.57mg/dl), high alkaline phosphatase (256 IU/L), normal intact parathyroid hormone(66.6pg/mL), normal morning cortisol(12.649μg/dL), normal TSH (1.238 uIU/ml)and normal free T4(1.435 ng/dl). Subsequent evaluation showed low 25-OH Vitamin D (24 ng/mL) and low 24 hour urine phosphorus (381.58mg/day).

Conclusion: Hypophosphatemia in the setting of complex bone disorders needs a careful evaluation. In clinical practice, we should evaluate all men diagnosed with osteoporosis carefully for secondary causes of bone loss.

PE10 VALIDATION OF A NEW METHOD FOR DETERMINING URINARY IODINE BY INDUCTIVELY COUPLED PLASMA MASS SPECTROMETRY

1,2LIN-HSUAN LEE,

1CHENG-PIN CHENG, 3YI-LIN LIU, 3WEI-LAN CHU,

1,4,5CHUN-JUI HUANG, 3,4,5CHEN-CHANG YANG, 1,6FAN-FEN WANG

1 Division of Endocrinology and Metabolism, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan; 2 Institute of Food Safety and Health Risk Assessment, School of Pharmaceutical Sciences, National YangMing University, Taipei, Taiwan; 3 Division of Clinical Toxicology & Occupational Medicine, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan; 4 Faculty of Medicine, School of Medicine, National Yang-Ming University, Taipei, Taiwan; 5 Institute of Public Health, School of Medicine, National Yang-Ming University, Taipei, Taiwan; 6 Department of Medicine, Yangming Branch, Taipei City Hospital, Taipei, Taiwan

Background: Urinary iodine concentration (UIC) has been traditionally determined by a modified microplate method utilizing the Sandell-Kolthoff (S-K) reaction in Taiwan. However, the S-K method consumes more time and produces toxic wastes from arsenic trioxide. The study aimed to develop and validate a new method for determining UIC by inductively coupled plasma mass spectrometry (ICP-MS).

Methods: Samples and iodate calibrators were diluted 100 times into aqueous solution containing triton X-100, 0.5% ammonia solution and tellurium (128Te) as an internal standard. Digestion was not necessary before analysis. A total of 183 excess urine samples covering a wide range of iodine concentrations were measured by both methods. Passing-Bablok regression and Bland–Altman plots were used to compare values across methods.

Results: The limit of detection by ICP-MS was 1 μg/L. For UIC values above 200 μg/L, the total coefficients of variation (CVs) were below 10%. Pearson correlation coefficient was 0.997, suggesting a high level of agreement between the two methods. The y-intercept for Passing-Bablok regression was 3.12 and the slope was 0.99. A small but neglectable mean difference of -0.8 μg/L was detected on Bland–Altman plots.

Conclusions: A simple, rapid, and accurate ICP-MS method has been validated for measuring UIC in Taiwan.

PE11 PATIENT ADHERENCE TO LOW IODINE DIET FOR PREPARATION OF RADIOACTIVE IODINE ABLATION THERAPY

1,2LIN-HSUAN LEE,

1CHENG-PIN CHENG, 3SHAN-FAN YAO, 1,5,6CHUN-JUI HUANG,

4,5,6CHEN-CHANG YANG,

3WEN-SHENG HUANG

1 Division of Endocrinology and Metabolism, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan; 2 Institute of Food Safety and Health Risk Assessment, School of Pharmaceutical Sciences, National Yang-Ming University, Taipei, Taiwan; 3 Department of Nuclear Medicine, Taipei Veterans General Hospital, Taipei, Taiwan; 4 Division of Clinical Toxicology & Occupational Medicine, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan; 5 Faculty of Medicine, School of Medicine, National Yang-Ming University, Taipei, Taiwan; 6 Institute of Public Health, School of Medicine, National Yang-Ming University, Taipei, Taiwan

Background: The degree of total body iodine depletion was considered to be related to the efficacy of radioiodine ablation therapy (RAIT) and was traditionally evaluated by random urinary iodine concentration (UIC) on the last day of low iodine diet (LID). However, changes in daily urinary iodine excretion varies greatly and one measurement could not truly reflect patient adherence to LID. The study aimed to determine patient adherence to LID and the possible dietary sources of iodine causing violation of LID.

Methods: Patients with papillary thyroid carcinoma scheduled for RAIT were recruited in Taipei Veterans General Hospital from March to October of 2020. Random spot urine samples were collected daily during the two weeks’ period of LID and a simple food frequency questionnaire (FFQ) was completed on the day of RAIT. The cut-off of urinary iodine/creatinine (I/Cr) ratio was set at 100 μg/ gCr. Violation of LID was defined as a mean UIC of three consecutive days above 100 μg/gCr since day 4 of LID.

Results: A total of 43 patients participated in the study and 58.1% (n = 25) of them stringently followed LID. Among the 41.9% (n = 18) who violated LID, three patients took iodine-containing nutritional supplement and seven patients did not avoid iodized salt. If only one measurement of urinary I/Cr ratio < 100 μg/gCr on the last day was used as the criteria to determine the degree of total body iodine depletion, 66.7% (n = 12) of the patients who violated LID would be misclassified as having good adherence to LID.

Conclusions: Despite years of experience in implementing LID in Taiwan, patient adherence remains suboptimal.

PE12 ECTOPIC CERVICAL THYMOMA-A CASE REPORT AND REVIEW

1ZI-JIAN LIN,

2SHU-YI WANG

1Division of Endocrinology and Metabolism, Department of Internal Medicine, Changhua Christian Hospital, Changhua City, Changhua County, Taiwan; 2Division of Endocrinology and Metabolism, Department of Internal Medicine, Changhua Christian Hospital, Changhua City, Changhua County, Taiwan

Thymomas are epithelial tumors of the thymic gland that usually arise in the anterior superior mediastinum. These tumors are rare neoplasms comprising less than 1% of adult cancers. Ectopic thymomas are thought to arise from aberrant thymic tissue displaced during embryologic development and are extremely rare, accounting for only up to 4% of all thymomas. This report described a 40-year-old woman who had a right-sided highly suspicious thyroid nodule, size: 3.9x 2.31x2.11 cm, by ultrasound with AmCAD-UT at health exam, without clinical symptoms including palpitation, dyspnea, hand tremor, or other immune disorders. Thyroid function was within normal range. Three times of fine-needle aspiration biopsies revealed negative for malignant cell. The histopathological diagnosis of the specimen after unilateral thyroid surgery was ectopic cervical thyroidal thymoma. Immunohistochemical stain reveals CK(+), TTF-1(-), INSM1(-), p63 diffuse(+), PAX8(+), GLUT1 diffuse(+), CD117 focal(+) and BCL2(+) for tumor cells. CD5(+) and Tdt focal(+) in scattered lymphocytes are seen. Radiotherapy has been shown to be an effective treatment, and it has a favorable prognosis. This case presented highlight an unusual tumor entity that can be clinically confused for common lesions affecting the thyroid gland.

PE13 DETERMINATION OF IODINE CONCENTRATION OF SOY SAUCE IN TAIWAN

1CHENG-PIN CHENG, 1,2LIN-HSUAN LEE, 1,3,4CHUN-JUI HUANG, 5WEN-SHENG HUANG

1 Division of Endocrinology and Metabolism, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan; 2 Institute of Food Safety and Health Risk Assessment, School of Pharmaceutical Sciences, National Yang-Ming University, Taipei, Taiwan; 3 Faculty of Medicine, School of Medicine, National Yang-Ming University, Taipei, Taiwan; 4 Institute of Public Health, School of Medicine, National Yang-Ming University, Taipei, Taiwan; 5 Department of Nuclear Medicine, Taipei Veterans General Hospital, Taipei, Taiwan;

Background: Soy sauce is widely used in a variety of Asian dishes to enhance flavor. Because soybean and most soybean products contain iodine, patients with thyroid carcinoma preparing for radioiodine ablation were educated not to ingest soy sauce during the two weeks’ period on a low iodine diet. The aim of the study was to determine the iodine contents of common domestic soy sauces.

Methods: Twenty-six different brands of soy sauce were diluted with distilled water with a dilution factor of fifty. Iodine concentrations of the diluted samples were measured colourimetrically based on the Sandell-Kolthoff reaction by a modified microplate method. All the measurements were repeated five times for determination of mean and standard deviation (SD).

Results: Among the twenty-six surveyed soy sauce, only three brands of soy sauce contained iodine. The iodine concentrations (mean ± SD) of the three iodine-containing soy sauces were 2.4 ± 0.4, 5.1 ± 0.4, 11.1 ± 1.0 mg/L respectively. The other twenty-three soy sauces were iodine-free. Two of the three iodine-containing soy sauce were supplied with kelp extract for additional umami, which were the major sources of iodine.

Conclusions: Most soy sauces were iodine-free and may be allowed on a low iodine diet.

PE14 A NEWBORN WITH CONGENITAL GOITER AND HYPOTHYROIDISM FROM A MOTHER WITH THYROTOXICOSIS: A CASE REPORT AND REVIEW OF LITERATURE

1YU-LIN YANG, 1CHUN-TA HUANG,

2WEI-HSIN TING,

3YI-YUNG CHEN,

1CHUN-CHUAN LEE

1Division of Endocrinology and Metabolism, Department of Internal Medicine, MacKay Memorial Hospital, Taipei 10449, Taiwan, R.O.C.; 2Division of pediatric endocrinology and diabetes, MacKay Memorial Hospital, Taipei 10449, Taiwan, R.O.C.; 3Division of High Risk Pregnancy, Department of Obstetrics and Gynecology, MacKay Memorial Hospital, Taipei 10449, Taiwan, R.O.C.

Background: Fetal goiter is a rare condition that affects one out of 30,000 pregnancies in iodinesufficient areas, usually in association with maternal Graves’ disease. Large goiters that obstruct fetal swallowing may lead to polyhydramnios and subsequent gastrointestinal dysgenesis, placing the pregnancy at risk of pre-term birth. Hyperextended neck caused by goiter and inadequate head flexion during labor increase the risk of neonatal respiratory distress as well as difficulties in intubation. Both neonatal hypothyroidism secondary to over-treatment of a thyrotoxicotic mother and neonatal hyperthyroidism due to transplacental passage of maternal auto-antibodies are possible etiologies. Nonetheless, it is not always easy to distinguish one from the other. Fetal ultrasound examination allows recognition of the goiter’s size but is unreliable to establish correct diagnosis. Maternal thyroid function and several fetal physiological parameters can provide important clues. Prompt adjustment of maternal anti-thyroid drugs and multidisciplinary team are crucial to avoid peri-partum complications.

Case presentation: A 34-year-old woman with underlying Graves’ disease, treated with PTU (250mg/day), had normal to slightly decreased level of free-T4 level and elevated TSHR-Ab level during the third trimester of pregnancy. She was admitted to our hospital at 37+5 weeks of gestation for elective caesarean-section owing to fetal goiter (thyromegaly) detected under pre-natal sonography. The infant presented with temporary symptoms of hypothyroidism that cured after thyroxine replacement.

Conclusions: The recommended perinatal management of Graves’ disease is to adjust free T4 within a range from the upper limit of normal to a slightly elevated level in order to maintain the thyroid function of the fetus.

PE15 LOCAL AND SYSTEMIC TREATMENTS IN A CASE OF METASTATIC DIFFERENTIATED THYROID CANCER WITH MULTIPLE TIMES OF RECURRENCE: A CASE REPORT AND REVIEW OF LITERATURE

1YVONNE CHIEW, 1CHEN-KAI CHOU

1 Division of Metabolism, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan.

Background: Various local and systemic treatments are available for metastatic differentiated thyroid cancer. Cryotherapy, radiotherapy frequency ablation (RFA) and target therapy were relatively uncommon comparing to metastatic surgery and radioactive iodine therapy (RAI). We present a case of metastatic differentiated thyroid cancer with multiple times of recurrence who underwent various treatment for metastatic lesions including RAI, surgery resection of metastatic nodules, RFA, cryotherapy, radiotherapy, and target therapy.

Case presentation: This is a 44-year-old woman diagnosed with right papillary thyroid cancer in 2017. She received total thyroidectomy in February of 2017 with initial staging of pT3Nx, followed by radioactive iodine(I-131) therapy (RAI, dose: 150mCi) in May of 2017 at other hospital. Cervical lymph node dissection was done in December of 2017, followed by RAI administration (100mCi, no uptake, accumulated dose: 250mCi) in March 2018 for thyroid cancer recurrence, stage pT4aN1b. As persistent high thyroglobulin level (Tg: 27ng/mL) was detected, she came to our hospital for second opinion. She suffered from multiple times of thyroid tumor recurrence and metastasis over neck, lung, and mediastinum area. She received total 3 times of RFA for metastatic nodules over neck, thyroid bed, paratracheal region and isthmus region in year 2018 and 2019. Wedge resection for lung metastasis and resection for mediastinum tumor were performed in year 2018 and 2019. In 2020, newly found pulmonary nodules over right lower lung and progressive increase in the size of soft tissue mass over sternal area with sternal bone destruction were detected by chest CT and PET. Cryotherapy was arranged for sternal tumor in April of 2020. She started target therapy with Lenvatinib 10mg per day since April 2020 and increased to 20mg per day since July 2020, her urine protein in April 2020 was negative. She received radiotherapy for sternal mass from May 2020 to June 2020. Her Tg level from October 2017 to April 2020 ranged from 27 to 423 ng/mL. Her image study showed tumor regression and her Tg level was decreasing (Tg level in October 2020: 10.8ng/ mL). Unfortunately, hypertension and proteinuria were noted since October 2020, antihypertensive medication was prescribed and her Lenvatinib dose was decreased to 8mg QD since then.

Conclusions: In metastatic thyroid cancer, surgery and RAI remain as the standard curative therapy. Unresectable regional and distant metastasis can be managed by local therapy such as cryotherapy, RFA and radiotherapy. Kinase inhibitor therapy can be offered in RAI refractory DTC

patients with rapidly progressive, metastatic cancer despite local treatments. The treatment should be patient-tailored, by weighing the risks and benefits, and put into consideration of life quality besides the risks of injury and death.

PE16 DIFFERENTIATED THYROID CANCER WITH BONE METASTASISTHREE CASES REPORT AND LITERATURE REVIEW

1YU-YEN TSAI, 1SHU-YI WANG

1 Division of Endocrinology and Metabolism, Department of Internal Medicine, Changhua Christian Hospital, Changhua City, Changhua County, Taiwan

In patients with differentiated thyroid cancer (DTC), bone metastasis (BM) is the second most common site of distant metastasis, usually associated with low survival rates. Diagnosis of DTC with BM is established by correlating clinical suspicion with imaging. The management of DTC with BM is challenging with regard to its heterogeneous courses, thus imaging is essential to detect, localize, and assess the lesions and should be used in conjunction with clinical evidence. This article includes 3 elderly female patients of DTC with BM, who initially presented with low back pain or abnormal soft tissue mass and was reported to be caused by bone metastasis according to imaging such as CT or MRI. Biopsies of the metastatic tumor in these patients all suggested a thyroid origin tumor. Specimen was obtained via bilateral total thyroidectomy, confirming the histopathological diagnosis of follicular carcinoma in two and papillary carcinoma in one of these cases. One of the patients with follicular carcinoma had undergone radiotherapy, radioactive iodine and kinase inhibitor of sorafenib. Subsequent whole body scans (WBS) and CT showed stable disease and decreased size of previous metastasis. The other two patients had also received radiotherapy and they will have radioactive iodine in the near future. These cases put an emphasis on accurate staging for appropriate follow-up, which allows early detection and improves treatment outcome. Furthermore, factors affecting metastatic susceptibility, such as gene expression profiles that predict the aggressive behavior of thyroid cancer cells, will be discussed, so as to provide more specific and personalized approach to achieve better disease control.

PE17 THYROID ECTOPIA, A CASE REPORT

1WAN-TING HUANG, 1BAO-YIN CHEN, 1YUN-SHING PENG, 1HO CHENG,

2MING-FONG TSAI,

1YUNG-HSIANG LIN

1Division of Endocrinology and Metabolism, Department of Internal Medicine, CGMH, Chiayi.

2Department of Nuclear Medicine, Chang Gung Memorial Hospital, Chiayi.

Background: Thyroid ectopia is a result of the failure of migration of the developing thyroid from the pharyngeal floor to its usual pre-tracheal region. It’s usually located along the normal path of thyroid descent. In 70% of all cases, the lingual thyroid gland is the only thyroid. It is rare for two ectopic thyroid tissue to be present simultaneously.

Case presentation: A 43 years old female presented with fatigue and weakness, was referred to our department due to hypothyroidism.(TSH:82.030 uIU/mL Free T4:0.76 ng/dL) Submental lump about 2 cm noted since childhood and a family history of thyroid disease(Her mother and younger brother) were mentioned during history taking. Physical examination revealed that the thyroid gland was not palpable. Thyroid ultrasonography confirmed the absence of thyroid gland and one isoechoic, heterogeneous solid nodule (2.36 x 2.29 x1.74cm) over the submandibular area found. Thyroid ectopia was suspected. Tc-99m thyroid scan was arranged to confirm the diagnosis. Anti-thyroid peroxidase antibody(anti-TPO ab.) was checked to survey the cause of hypothyroidism.

Results: Tc-99m thyroid scan revealed non-visualization of thyroid gland in the thyroid beds bilaterally. And, there was obvious radioactivity in the submandibular and upper mediastinum, left lower to the thyroid bed. Anti-TPO ab. revealed high titer(592.92 IU/mL). Dual thyroid ectopia with autoimmune thyroid disease related hypothyroidism was impressed. Thyroxine replacement was started. I-131 thyroid scan and SPECT/CT image fusion study will be arranged for confirmation and localization of the impressed thyroid anomaly.

PE18 COMPLETE ANDROGEN INSENSITIVITY SYNDROME: A CASE REPORT

1JIAN-YU JHU, 1SHIH-HUI HUANG,

1YI-LUN CHIANG,

1SHIH-MING LAI,

1YEN-LING CHEN,

1CHUNG-YEN HUANG, 1,2HONG-DA LIN, 1PEI-CHI CHEN

1 Division of Endocrinology, Shin Kong Wu Ho-Su Memorial Hospital, Taipei, Taiwan; 2 Division of Endocrinology, Taipei Veterans General Hospital, Taipei, Taiwan

Background: Androgen insensitivity syndrome is an X-linked recessive genetic disease. Mutations in the androgen receptor gene are 70% inherited and 30% de novo. Prevalence of complete androgen insensitivity syndrome is around 1/20400 to 1/99100. Patients present female external genitalia with a 46 XY karyotype at birth and primary amenorrhea at puberty. Normal breast development and absence of pubic hair were found due to complete androgen receptor dysfunction. High Luteinizing hormone and testosterone level were also noted.

Methods: We reported a 16 years old female with complete androgen insensitivity syndrome who received laparoscopic orchiectomy and estrogen replacement therapy.

Results: A 16 y/o female denied any systemic disease before. Her grandmother accompanied with her to our endocrine clinic due to amenorrhea, while. she did not complain any other discomfort. Physical examination showed normal breast development (Tanner stage IV-V) and absence pubic and axillary hair (Tanner stage I).

The patient denied any sexual experience before and the pregnancy test was negative. Luteinizing hormone (LH 44.53 mIU/mL), follicle stimulating hormone (FSH 46.3 mIU/mL) and testosterone (5.47 ng/mL) all were higher than female normal range in her age. Pelvic echo showed no uterus nor adnexa. Genetic test was done, and karyotype revealed 46 XY. Abdominal CT revealed testis at lateral aspect of bilateral pelvic cavity, so she was transferred to division of urology. Laparoscopic orchiectomy was done. After surgery, estrogen replacement therapy was given to keep her female characteristics.

Conclusions: Almost all patients with complete androgen insensitivity syndrome received gonadectomy and hormone replacement therapy after surgery, but the timing of gonadectomy is still controversial. Delay of operation is more considerable nowadays because the tumor risk of testes with complete androgen insensitivity syndrome is low before the puberty peroid.

PE19 THERAPEUTIC INHIBITION OF POLO-LIKE KINASES IN ANAPLASTIC THYROID CANCER

1,2,3SHU-FU LIN, 3,4CHUN-NAN YEH, 5YU-TUNG HUANG, 6,7TING-CHAO CHOU,

8RICHARD WONG

1Department of Internal Medicine, New Taipei Municipal TuCheng Hospital, New Taipei City, Taiwan;

2Department of Internal Medicine, Chang Gung Memorial Hospital, Taoyuan, Taiwan; 3Chang Gung University,

Taoyuan, Taiwan; 4

Department of Surgery, Chang Gung Memorial Hospital, Taoyuan, Taiwan; 5Center for Big Data Analytics and Statistics, Chang Gung Memorial Hospital, Taoyuan, Taiwan; 6Laboratory of Preclinical Pharmacology Core, Memorial Sloan-Kettering Cancer Center; 7PD Science, Inc., 599 Mill Run, Paramus, NJ, USA; 8Head and Neck Survice, Memorial Sloan-Kettering Cancer Center

Background: Polo-like kinases (PLKs) are potent regulators of cell proliferation and cell survival. PLKs are potential targets in the treatment of anaplastic thyroid cancer (ATC), a rare but deadly disease.

Methods: The therapeutic efficacy of volasertib, a PLKs inhibitor, alone and in combination with sorafenib, for treatment of ATC was evaluated in vitro. The expression of PLKs was assessed using Western blot. Cell cycle distribution was measured by flow cytometry and immunofluorescence microscopy. Apoptosis and caspase-3 activity were evaluated by flow cytometry and fluorometric assay. Mice bearing flank ATC were treated with volasertib and sorafenib.

Results: Volasertib decreased cell viability in three ATC cell lines (8505C, 8305C, and KAT18) in a dose-dependent manner. Volasertib caused ATC cells to accumulate in G2/M phase, activated caspase-3 activity, and induced apoptosis. Combination therapy of volasertib and sorafenib in ATC cells showed mostly synergistic effects. In vivo studies revealed that combination therapy of volasertib and sorafenib was effective in the treatment of 8505C xenografts. Single-agent volasertib treatment was sufficient to retard 8305C tumor growth. No substantial morbidity was observed in animals treated with either single agent or combination treatment.

Conclusions: These preclinical findings suggest that volasertib may be an effective drug in treating ATC.

PE20 PULMONARY CRYPTOCOCCOSIS AND MULTIPLE VERTEBRAL FRACTURES AS INITIAL PRESENTATIONS OF ADRENAL CUSHING’S SYNDROME

1KUAN-YU LIN, 2TSONG-YOW WU, 1CHIH-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.

Background: Complications of untreated Cushing’s syndrome included hypertension, impaired glucose tolerance, osteoporosis and susceptibility to infections. However, literature regarding pulmonary fungal infections as initial presentations of Cushing’s syndrome were rare.

Methods: We presented a case of adrenal Cushing’s syndrome with rare initial presentations of pulmonary cryptococcosis and multiple vertebral fractures.

Results: This 57-year-old woman was diagnosed with papillary thyroid cancer and received total thyroidectomy 6 years ago before this evaluation. A right lower lobe nodule, 1 cm in diameter, was accidentally found by low dose CT 29 months ago, and was enlarged to 1.5 cm in diameter one year later. She received video-assisted thoracoscopic tumor wedge resection 14 months before this evaluation, and the pathology revealed pulmonary cryptococcosis. She received fluconazole 400 mg daily for 6 months postoperative. On the other hand, pre-operative CT revealed a 2.8 cm right adrenal nodules and T7 spine compression fracture. She had a fall episode while skiing one month earlier. A DEXA scan performed later revealed osteoporosis, with lumbar T score of -4.5. Oral calcium and calcitriol supplement, with monthly teriparatide injection were prescribed. Additional history taking revealed that she had hypertension, hyperlipidemia and weight gain of more than 10 kilograms in recent 5 years. The patient’s vital signs were stable. She was obese, with some supraclavicular and posterior neck fat pads deposition. There were no typical Cushingoid features like moon face, purple striae or proximal myopathy. Laboratory examinations revealed increased neutrophils counts, decreased lymphocyte counts, mild hypernatremia and hypokalemia. Serum cortisol levels were within upper normal limit, but without diurnal change (8 AM 17.10 μg/dl, 4 PM 15.30 μg/dl, reference range 8 AM 3.7 - 19.4 μg/dl, 4 PM 2.9 - 17.3 < 1.8). Serum ACTH level was low. One milligrams dexamethasone suppression test failed to suppress morning cortisol level, and 24-hr urinary free cortisol was elevated. Serum aldosterone, plasma renin activity, 24-hr urinary catecholamines and VMA level were all within normal range. Under the diagnosis of adrenal Cushing’s syndrome, the patient received laparoscopic right adrenalectomy. The pathology revealed cortical adenoma. The postoperative course was uneventful. She lost 9 kilograms in 3 months after surgery. She felt well under oral cortisone supplement at a dose of 25 mg in the morning and 12.5 mg in the afternoon.

Conclusions: Clinical awareness of atypical presentations of Cushing’s syndrome is important. Single-point, morning cortisol level may not accurately reflect the severity of corticosteroid excess, and further dynamic tests are warranted if high clinical suspicions. Early diagnosis and treatment of Cushing’ syndrome prevent long-term sequelae such as severe infections and osteoporosis.

PE21 ANTERIOR NECK HEMATOMA WITH TRACHEAL COMPRESSION AFTER FINE-NEEDLE ASPIRATION CYTOLOGY OF THYROID: A RARE BUT PRECAUTIOUS COMPLICATION IN ENDOCRINE PROCEDURE

1TSONG-YOW WU, 2KUAN-YU LIN,

2CHIH-YUAN WANG

1Department of Internal Medicine, National Taiwan University Hospital, Taiwan, R.O.C.; 2 Division of Endocrinology and Metabolism, Department of Internal Medicine, National Taiwan University Hospital, Taiwan

Background: Fine needle aspiration cytology (FNAC) is usually the routine diagnostic pathway to assess lesions of the thyroid gland. The simple technique was considered to be a relatively costeffective and low risk methodology for initial differentiating benign nodular goiter from malignant one.

Methods: We presented a case of right neck progressively swelling with tracheal compression after fine-needle aspiration of thyroid.

Results: This 62 year-old man has been regularly followed up at an endocrinologist's outpatient-clinic for his acromegaly and bilateral multinodular goiter. Blood tests on 2019/08/09 showed elevation of serum thyroiglobulin (182 ng/ml). Thyroid sonography on 2019/9/03 showed enlargement of right cystic goiter (5.82 x 5.118 x 3.31 cm). Fine-needle aspiration was suggested but postponed to 2019/9/10 due to taking fish oil. He denied taking any anti-platelet or anti-coagulant. Fish oil was discontinued for one week and fine-needle aspiraiton was performed to right cystic lesion at 15:00 on 2019/9/10. Total 25 c.c dark brownish fluid was drained. After aspiration, the thyroid echo showed decreased thyroid cyst and no actvie bleeding. However, progressive pain and swelling of the right neck developed in the following hours. No dyspnea or stridor was noted. Due to above reasons, he came to our emergency department for help. Head and neck CT-scan showed a large hematoma at the anterior right lower neck, mainly from the thyroid gland, with contrast extravasation. The trachea was compressed and displaced to the left side. Trans-arterial embolization was indicated but respiratory distress in supine position developed. Therefore, endotracheal tube intubation was performed for airway protection. Trans-arterial embolization was done smoothly and he received intensive care thereafter. Fortunately, he recovered smoothly and discharged from hospital three weeks later.

Conclusions: Although FNAC is a relatively safe procedure for detecting the cytological findings of nodular goiter, the associated complications, including hemorrhage, incidental trauma around soft tissue, infection, inflammatory response still should be concerned. Pre-procedural preparation with delicate survey of probable routine medications, coagulopathy and healthy food will be pivotal, together with gentle procedure with sono-guided aspiration technique.

PE22 FAMILIAL THYROID PAPILLARY CARCINOMA: A CASE REPORT

HUI-LING LIN, TSUNG-HUI WU, TANG-YI LIAO, FANG-YU CHEN, CHII-MIN HWU

Section of Endocrinology and Metabolism, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan

Background: Familial papillary thyroid carcinoma (FPTC) is rare, and it is defined as the same diagnosis in three or more first-degree relatives in one family. It’s believed that FPTC is more aggressive with higher rates of recurrence, comparing to sporadic PTCs.

Methods: We report a series cases of familial follicular thyroid carcinoma.

Results: The 49-year-old male accidentally found a left neck mass during a health examination in January 2012. According to the patient, he had heat intolerance for years. There were also general malaise and easy sweating at night. However, the patient denied body weight loss or palpitation. Thus he came to the other hospital for further survey, and thyroid sonography revealed a thyroid mass of 2.8 cm, whereas fine needle aspiration showed benign nature. The patient came to our hospital for regular following up then. In May 2013, aspiration cytology revealed thyroid papillary carcinoma. Total thyroidectomy with central lymph node dissection was prescribe on 2013-07-19. Total 2 tumors, size 0.3 cm and 3.5x3x2 cm were found, pTNM stage is pT2N0Mx. Then we let the family come for further evaluation. His mother was diagnosed with micro papillary thyroid carcinoma in 2015. His 1st young brother received right lobectomy for 7cm right neck mass in 2015, pathology revealed nodular goiter with cystic degeneration. In 2020, his 2nd younger brother was also diagnosed with papillary thyroid carcinoma. Due to above description, familial papillary thyroid carcinoma is diagnosed.

Conclusions: Regular following up of first-degree relatives should be considered when papillary thyroid carcinoma is diagnosed.

PE23 THYROTROPIN (TSH)-SECRETING PITUITARY ADENOMAS - CASE REPORT AND ANALYSIS OF CLINICAL FEATURES AND TREATMENT IN A 5-YEAR CASE SERIES IN NATIONAL TAIWAN UNIVERSITY HOSPITAL

1CHUN-HSIEN LIN, 3HSIN-YI HUANG,

2PO-HAO HUANG, 2SHIH-HUNG YANG,

1JIN-YIN LU, 1WAN-CHEN WU

1Division of Endocrinology and Metabolism, Department of Internal Medicine, National Taiwan University Hospital; 2Division of Neurosurgery, Department of Surgery, National Taiwan University Hospital; 3Department of Pathology, National Taiwan University Hospital

Background: Thyrotropin (TSH)-secreting pituitary adenomas (TSH-omas) is a rare pituitary adenoma, accounting for 0.5-3% of all functioning pituitary adenomas. According to the 2017 WHO classification, it may be classified as thyrotroph adenoma or plurihormonal adenoma. We reported a case of thyrotroph adenoma, and presented analysis of clinical symptoms, diagnosis, treatment and prognosis in a 5-year TSH-omas case series in National Taiwan University Hospital (NTUH).

Case Report: A 68-year-old female without known systemic diseases was presented to the emergency department due to recurrent vertigo and hypertension. The neurological examination was unremarkable. However, blood tests showed high free T4 (fT4) (2.15 ng/dL) with non-suppressed thyroid stimulating hormone (TSH) (4.96 μIU/mL). She had no obvious symptoms related to thyrotoxicosis, and there was no family history of thyroid diseases. Repeated blood tests using different laboratory methods showed the same results, and central hyperthyroidism was suspected. The pituitary MRI revealed a 1.2 cm adenoma at right pituitary gland with stalk deviation to the left side. Other pituitary hormones were all within normal limits. Thyrotropin-releasing hormone (TRH) stimulation test yielded blunted response and octreotide suppression test showed TSH was well suppressed, compatible with TSH-oma. Octreotide 100 mcg per 8 hours was administered for 7 days and endoscopic transsphenoidal adenomectomy was performed. The immunohistochemistry (IHC) stain showed strong positive of β-TSH and negative of other pituitary hormones, compatible with thyrotroph adenoma. Transient central hypothyroidism occurred within a few months after surgery, and was replaced with levothyroxine for around 6 months. There was no residual tumor in MRI, lab profile showed euthyroid state without levothyroxine replacement, the vertigo resolved and hypertension was well controlled at current 1.5-year follow up.

Method: We retrospectively enrolled cases diagnosed with TSH-omas and received surgery from 2016/1 to 2020/12 in NTUH. The diagnosis of TSH-omas included blood test showed central hyperthyroidism and the pathology confirmed thyrotroph adenoma or plurihormonal adenoma by 2017 WHO classification criteria. We analyzed these patients' clinical features, treatment, and prognosis.

Results: A total 378 patients had pituitary tumor and underwent pituitary surgery, and the pathology of 344 patients showed pituitary adenoma. 22 of the 344 pituitary adenomas (6.4%) showed positive IHC stain of TSH. Only four cases (1.2%) fulfit the diagnosis of TSH-omas. Two of them were thyrotroph adenoma, and blood tests showed central hyperthyroidism without abnormalities in other pituitary hormones. The other two cases were plurihormonal PIT1-positive adenomas. Laboratory data of both showed also central hyperthyroidism, but one had combined high hGH and IGF-1 level, who had obvious acromegaly features. These four patients were all women without any systemic diseases, and the age of diagnosis was 24 to 68 years old. The initial presentations were blurred vision, vertigo, dysmenorrhea, and insomnia/dizziness respectively. The thyroid function tests were fT4 1.79-3.98 ng/dL and TSH 3.57-5.32 μIU/ml. Two of them had some symptoms which may be related to hyperthyroidism, such as hypertension and menstrual irregularity, and the other two had no obvious related symptoms. Two of them also had a combination of autoimmune thyroid disease diagnosed by positive thyroid auto-antibodies and sonographic characters. TRH stimulation tests and octreotide suppression tests were performed in 3 patients. Two showed blunted TSH response to TRH and well suppressed TSH to octreotide, and one showed borderline TSH response to TRH, and partially suppressed TSH to octreotide. Three of them received octreotide therapy before operation, three patients had transient diabetes insipidus. Three patients returned to euthyroid state However, one had persistent hyperthyroidism 2 months after surgery, and underwent further evaluation recently.

Conclusions: TSH-oma is a rare functioning pituitary adenoma. Patients with TSH-oma may not always present typical thyrotoxic symptoms. For patients whose blood tests showed elevated fT4 with non-suppressed or elevated TSH, doctors should be aware of “inappropriate secretion of TSH (IST)”, and TSH-oma is one of the causes. Management of TSH-oma and primary hyperthyroidism are completely different. If TSH-oma is misdiagnosed as primary hyperthyroidism, and treated with antithyroid drugs, which may aggravate TSH-oma. The other important differential diagnosis of IST is resistance to thyroid hormone (RTH), which can be differentiated from family history, pituitary imaging, TRH stimulation test, and response test to somatostatin analogue.

PE24 ADRENAL INCIDENTALOMA WITH AUTONOMOUS CORTISOL SECRETION AND UNCOMMON PATHOLOGICAL FINDING

1CC KU, 1YM CHIEN, 2HM CHAO, 1CJ CHANG,

1,3,4TI LEE, 1,4TW LEE

1

Division of Endocrinology and Metabolism, Department of Internal Medicine, Wan Fang Hospital; 2Department of Pathology, Wan Fang Hospital; 3Department of General Medicine, School of Medicine, College of Medicine, Taipei Medical University; 4Division of Endocrinology and Metabolism, Department of Internal Medicine, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan

Background: Adrenal incidentaloma may present with autonomous cortisol secretion, a state of hypercortisolism without prominent clinical features of Cushing’s syndrome, causing diabetes mellitus, hypertension, osteoporosis, and obesity.

There existed controversy in whether adopting surgical resection as an optimal therapeutic choice.

Patient's therapeutic strategy needs to be individualized based on efficacy and benefit.

Case Presentation: A 69-year-old woman has type 2 diabetes mellitus for 14 years, hypertension, and hyperlipidemia.

She was incidentally found to have a 1.5 cm tumor over left adrenal gland by abdominal noncontrast computed tomography on 2019/02/25. (Figure 1).

Hormone work-up ruled out the diagnosis of primary aldosteronism (Table 1) and pheochromocytoma (Table 2).

Physical examinations showed no clinical features of hypercortisolsim related abnormality such as moon facies, buffalo humps, purple striae, and thin skin. 1mg overnight dexamethasone suppression test (DST) showed nonsuppressible cortisol levels: 5.457pg/ml on 2019/6/21.

Repeated 1mg overnight DST, which was adopted in order to verify the biochemical authenticity of diagnosis because of discrepancy between 24 hour urine free cortisol level and 1mg overnight DST, also showed nonsuppressible cortisol levels: 4.43pg/ml on 2019/8/17. (Table 3)

The patient underwent left laparoscopic adrenalectomy on 2019/12/18, a golden yellow nodule (A) and another dark brown pigmented nodule (B) were found on the left adrenal gland (Figure 2).

Pathological examination revealed macronodular hyperplasia (Figure 3).

Based on the results of biochemical studies and pathological findings, ACTH-independent macronodular hyperplasia (AIMAH) was impressed.

Post-operatively, the patient’s antidiabetic and antihypertensive drugs were reduced.

Better glycemic control with lowering AC glucose 92mg/dl, PC glucose 152mg/dl, and HbA1c 4.5% in contrast to each counterpart with 184mg/dl, 326mg/dl, 9.3% at 2019/12/7 before operation were noted.

Discussion: Autonomous cortisol secretion accounts only 5.7% of all adrenal incidentalomas.

AIMAH commonly presents with bilateral adrenal gland enlargement and multiple adrenal nodules.

Our patients had only left adrenal gland nodule, which might be mistaken as a common unilateral adrenal adenoma.

Either bilateral adrenalectomy or pharmacological inhibition of autonomous cortisol secretion would be treatment option.

Age, degree of cortisol excess, general health, comorbidities and patient’s preference should be taken into account in patients with adrenal incidentaloma and autonomous cortisol secretion considered for adrenal surgery.

Our case suggested that adrenalectomy is beneficial in patients with autonomous cortisol secretion and associated comorbidities, such as hypertension and diabetes mellitus.

Conclusions: Adrenal surgery in patients with adrenal incidentaloma and autonomous cortisol secretion may lead to improved glycemic and blood pressure control.

PE25 A COEXISTENCE OF TSH-SECRETING AND GH-SECRETING PITUITARY TUMOR: A CASE REPORT

1YOU-TING LIN,

1TZU-YUAN WANG, 1MING-JIA XIE, 1CHING-CHU CHEN,

1CHWEN-TZUEI CHANG,

1RONG-HSHING CHEN, 1JUN-WEI HO, 1JUEI-YU TSENG,

1JIA-YIN GUO, 1YING-YU TSENG

1Intelligent Diabetes Metabolism and Exercise Center, Department of Internal Medicine, China Medical University Hospital, Taichung, Taiwan

Background: While full-blown forms of acromegaly due to growth hormone-secreting tumor are often easily recognizable clinically, co-secreting thyrotropin (TSH) and growth hormone (GH) pituitary adenomas are rarely reported.

Case report: A 50-year-old man with a history of hypertension, valvular heart disease and atrial fibrillation was sent to emergency room at local clinic due to traffic accident without head trauma. After conservative treatment, he was informed further investigations is needed because of the high index of suspicion for features of acromegaly. He has had hypertension and atrial fibrillation for 5 years and regularly sees his cardiologist, which are controlled on olmesartan medoxomil 20 mg daily, furosemide 40mg daily, spirolactone 25mg daily, rivaroxaban daily, and digoxin 0.25 mg daily. At our neurosurgery outpatient department, a hGH level of 7.011 ng/mL (<1 ng/mL), insulin-like growth factor-1 level of 607 ng/mL (48.1-209 ng/mL), free T4: 3.86 ng/dL (0.54-1.40 ng/dL). Other laboratory test results, including complete blood cell count, routine chemistries, anterior hormonal data including TSH, ACTH, cortisol, LH, FSH, testosterone, prolactin, are all normal. The initial pituitary-dedicated MRI documents a lobulated tumor measuring 26x25x23 mm in the enlarged pituitary fossa, left cavernous sinus involvement, encasement of left internal carotid artery, and mild suprasellar bulging. Cardiac echography shows a dilated aortic root and multiple moderate valvular regurgitations including aortic, tricuspid, mitral and pulmonary valve. The neurosurgeon requests an endocrine consult preoperatively. On physical examination, his height is 176 cm and weight is 94.6 kg (BMI: 30.5 kg/m2). His blood pressure is 165/82 mm Hg and pulse rate is 102 beats/min with irregular rhythm and systolic murmur grade 3, enlarged nose, macroglossia, protruding jaw, big hands and feet, and lower extremity edema. 75 gram of glucose fails to suppress the 6 time-serial hGH level by a 2-hour GH-suppression test. The thyroid stimulating immunoglobulin, antithyroid peroxidase antibody, and antithyroglobulin antibody are all below the reference range, and thyroid echography demonstrates a symmetrically enlarged thyroid. All above clinical presentations and studies are suggestive of a coexistence of TSH-secreting and GH-secreting pituitary tumor. Due to the high risk of transsphenoidal surgery under not well controlled cardiac failure, long-acting somatostatin analogue and gamma knife radiosurgery are clinically feasible alternative measure.

Conclusion: Clinician should be able to cognizant of the clinical presentations of acromegaly and the potentially of other co-secreting hormone such as, though its rarity, the TSH, even in the absence of relevant symptoms. Control of co-secreting GH and TSH pituitary macroadenomas is possible with somatostatin analogue and gamma knife radiosurgery.

PE26 PSUDOHYPOPARATHYROIDISM?! OR PSEUDOPSEUDOHYPOPARATHYROIDISM ??!

1CHIA-TE WU, 1CHING-LING LIN,

1LI-CHI HUANG, 1WEI CHANG CHEN,

1TIEN-SHANG HUANG

1Division of Endocrinology and Metabolism, Department of Internal Medicine, Cathey General Hospital.

Introduction Psuedopseudohypoparathyroidism(PPHP) is an extremely rare genetic disease, unlike other forms of pseudohypoparathyroidism(PHP) usually comes with resistance to PTH, which is characterized by a constellation of clinical features collectively termed Albright hereditary osteodystrophy (AHO) but no evidence of resistance to parathyroid hormone (PTH). Here we presented with a case.

Case Report On 2018/07/17, A 15-year-old adolescent female came to our Metabolic Endocrinology outpatient clinic due to obesity(115kg) and progressive weight gain for 8 years. On examination, she had short stature (155 cm) and shortened 4th and 5th fingers bilaterally. Hand radiographs confirmed symmetric (AHO-like ) abnormalities of both hands with shortening at the right 4th metacarpal bone and left 3rd & 4th metacarpal bone. Cushingoid features with moon facies, buffalo hump, purple striae, and acanthosis nigricans on the posterior neck were noted as well. She had no ectopic calcifications on the chest radiograph, serum calcium and phosphate were normal as well as intact parathyroid hormone (i-PTH) levels (26.4pg/ml). Cushing syndrome had been ruled out after over-night and standard two days dexamethasone suppression test were repeated for 2 times. Molecular genetic testing was performed however it showed no evidence of mutation in her GNAS gene. Based on her clinical presentation and hormonal and biochemical profile, the diagnosis of pseudopseudohypoparathyroidism was concluded.

Discussion Obesity in adolescents is a common issue due to several environmental, medical, or physiological reasons. However, when obesity combined with brachydactyly, few congenital anomalies should be kept in mind especially PHP and its varients. Diagnosis of PPHP is based on the presence of typical features of AHO (X-rays confirmed shortening of the fourth metacarpal) and exclusion of other forms of PHP (by measuring serum calcium, phosphate, and iPTH which are typically normal in PPHP). Molecular genetic testing in PHP might showed mutation in the coding sequence of GNAS gene (the maternal allele) in PHP1a; abnormal methylation at the GNAS A/B:TSS-DMR in PHP1b; mutation in the coding sequence of GNAS gene (the maternal allele)(exon 13 preferentially) in PHP1c and mutation in the coding sequence of GNAS gene (the paternal allele) in PPHP. However, the sensitivity of the molecular genetic testing is only 50-72% thus negative result should not exclude the diagnosis. For our patient, the diagnosis of PPHP is based on her typical AHO feature with negative hormonal and biochemical laboratory result.

Pseudopseudohypoparathyroidism is not life-threatening but the quality of life can be affected in those with severe ectopic ossification. Currently, no treatment is required but genetic counseling is recommended.

PE27 RADIOFREQUENCY ABLATION FOR LOCALLY INVASIVE PARATHYROID CARCINOMA: A CASE REPORT

1WEI-CHANG CHEN, 1CHING-LING LIN

1Department of Endocrinology and Metabolism, Cathy General Hospital, Taipei, Taiwan

Case presentation: A 63 years old female patient under thyroxine treatment due to left partial thyroidectomy about 45 years ago for nodular thyroid disease. In 2008, primary hyperparathyroidism was diagnosed due to severe hypercalcemia (15.4mg/dL) with chondrocalcinosis. Post-operative serum calcium return to normal range with surgical removal of a 4.45x3.01x2.59 cm parathyroid tumor from right thyroid bed. Serum i-PTH level as well as calcium elevated shortly after initial normalization postoperatively. Repeated parathyroid scan showed residual parathyroid tissue in right upper thyroid bed and thyroid echogram showed a hypoechoic lesion in upper right thyroid bed with intrusion into airway lumen through thyroid cartilage. As patient was in good general wellbeing and further radical resection may cause major function destruction, Cinacalcet was used since 2012/09 for treating hypercalcemia with dose up-titrated to 75 mg/day but hypercalcemia persisted and eventually she could not tolerate such high dose of Cinacalcet due to recurrent diarrhea therefore dose of Cinacalcet was tapper down to 50 mg/day. During this period, her DM improved as well as her low BMD and she remained free of symptoms although her serum level remained elevated around 1213 mg/dL. However, deterioration of renal function and persistent nephrocalcinosis were noted and followed larynx CT (2018/08) showed 1.6 cm bi-lobular lesion at right upmost thyroid bed and right subglottic luminal area causing mild airway obstruction. For renal function preservation, correction of persistent hypercalcemia through debulking surgery was performed through intra-laryngeal approach and the lesion was partially removed however hypercalcemia persisted. Echo-guided radiofrequency ablation (RFA) of residual tumor through transcutaneous approach was performed on 2019/05/23 and hypercalcemia resolved and level of parathyroid hormone declined as tumor volume furtherly reduced by RFA and her renal function stabilized thereafter.

Discussion: Hypercalcemia is a common clinical problem and is mostly caused by primary hyperparathyroidism or malignancy. Severe hypercalcemia which is defined as calcium > 14 mg/dL is associated with more severe symptoms and required immediate therapy. Parathyroid carcinoma is a rare cause of primary hyperparathyroidism which accounts for 1-2% and it is commonly associated with severe hypercalcemia(65-75%). Diagnostic criteria of parathyroid carcinoma include: 1. local invasion of contiguous structures or 2. lymph node or distant metastases. Surgery is the mainstay of therapy for initial treatment, locally recurrent or metastatic disease of parathyroid carcinoma. Medical therapy, including bisphosphonate, denosumab and Cinacalcet is used to control persisted hypercalcemia or unresectable disease. RFA is currently indicated for symptomatic benign thyroid

nodule and may indicate for palliative treatment for unresectable thyroid cancer but seldom use for parathyroid cancer with hypercalcemia. In this case, we use RFA to shrink the mass and normalize serum calcium level without major functional destruction and resulted in stabilization of patient’s renal function. Since unresectable parathyroid carcinoma is a rare clinical condition the indication of and effectiveness of RFA in this kind of patients remains to be an open question.

PE28 THE ASSOCIATION BETWEEN HEMORRHOID AND GRAVES' DISEASE

1,2HSIN -HUNG CHEN

1 Division of Endocrinology and Metabolism, Department of Internal Medicine, Asia University Hospital, Taichung, Taiwan; 2 Chung Sheng clinic, Nantou, Taiwan

Background: To investigate the association between Graves’ disease (GD) and hemorrhoid

Methods: Patients with at least two out-patients and one admission record of ICD-9-CM disease code 455.1-455.5 and 455.8 were defined as hemorrhoids patients in this study. Hemorrhoids patients and control patients were matched by sex, age and co-morbidities in the ratio of 1:4.The incidence of GD (ICD-9-CM code 242.0) was the primary event in this study. The Cox proportional hazard model was used to estimate the risk of GD. Univariable model was used to estimate crude hazard ratio (HR) and the multivariable model was used to estimate the adjusted HR. The cumulative incidence curves were obtained by the Kaplan-Meier method and assessed by the Log-rank test.

Results: We recruited 13,165 hemorrhoids patients and 52,660 control patients in this study. The mean follow up time was about six years. The incidence rate of GD in patients with hemorrhoids was 1.57 per 1,000 person-years and that in the controls was 1.13 per 1,000 person-years. The risk of GD increased by 1.39 times (95% CI = 1.13, 1.71) in hemorrhoids patients compared to the control patients. Female patients with hemorrhoids had a higher risk of GD than those without hemorrhoids (adjusted HR = 1.44; 95% CI = 1.13, 1.83). People in age group 30-39 and suffered with hemorrhoids were more likely to develop Graves’ (adjusted HR = 1.73; 95% CI = 1.18, 2.55).

Conclusions: According to our analysis, the incidence rate of GD in patients with hemorrhoids was higher. Compare to non hemorrhoid group, Patients who were female and younger were the high risk group for GD in the hemorrhoid group.