OE：Oral presentation-Endocrine (1-6

OE-1 URINARY EXOSOMAL BIOMARKERS IN THYROID CANCER PATIENTS WITH ABLATIVE THERAPY: A PILOT STUDY

1TSE-YING HUANG, 2,3CHIH-YUAN WANG, 2LI-TING HUANG, 2YI-CHIEH CHUNG

1Department of Internal Medicine, National Taiwan University Hospital, Hsin-Chu Branch, Taiwan; 2Division of Endocrinology and Metabolism, Department of Internal Medicine, National Taiwan University Hospital, Taiwan; 3Department of Internal Medicine, National Taiwan University Hospital, Yunlin Branch,Taiwan

Background: Although thyroid cancers are low-grade endocrine malignancy, most patients usually received thyroidectomy with ablative radioactive iodine therapy. Such patients were followed with thyroid ultrasonography and serial serum thyroglobulin evaluation.

Methods: Exosomes are nanovesicles secreted into extracellular environments. Cancer cellderived exosomes could be found in plasma, saliva, urine and other body fluid of patients with cancer. We try to analyze the urinary exosomal proteins, including thyroglobulin and galectin-3, to find the early prognostic biological markers in urine via this prospective study.

Results: The trends of urinary thyroglobulin concentrations in patients with post-ablative thyroid cancer were detected in the very first three patients. Importantly, serum thyroglobulin cannot be found in two patients after radioactive I-131 ablation, however, urinary exosomal thyroglobulin still showed an increasing trend.

Conclusions: Since expensive recombinant human TSH (rhTSH) is usually needed to stimulate serum thyroglobulin for detecting local recurrence or distant metastasis. The issue of earlier biological markers for predicting prognosis of thyroid cancer should be raised. This pilot study report is the very first one to explore that urinary exosomal thyroglobulin could be a reliable biological marker to substitute for serum thyroglobulin in the future.

OE-2 COMPARISON OF DIAGNOSTIC METHODS FOR THE DETECTION OF A BRAF MUTATION IN THYROID NEOPLASM

1YUNG-NIEN CHEN, 2SHUN-CHEN HUANG, 1JUNG-FU CHEN, 1CHEN-KAI CHOU

1Division of Metabolism, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan; 2Department of Pathology,Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan

Background: Papillary thyroid carcinoma (PTC) represents the majority of differentiated thyroid cancers, presenting the V600E activating BRAF mutation in 29–83% of cases. The most accurate and robust method for detecting the BRAF mutation has not yet been determined. BRAF mutational analysis was performed by Sanger DNA sequencing, competitive allele-specific real-time polymerase chain reaction (CasPCR) and digital polymerase chain reaction (dPCR).

Methods: To compare sensitivity and accuracy of three methods for detection of BRAF mutation, mixed proportion of BCPAP (BRAF mutant) cells and TPC1 (BRAF-negative) wild type were assessed. DNA extracted from 94 thyroid tumors (30 classical papillary thyroid carcinomas (PTC); 29 follicular PTCs; 15 goiters; 10 Hashimoto’s thyroiditis; 10 Graves’ disease) were also used for detection of BRAF mutations by dPCR.

Results: To compare the sensitivity of different methods for detection of BRAF mutation, mutant BRAF DNA samples were tested in diluted mixtures of mutant and wild type. Digital PCR, but not CasPCR(9%) or Sanger sequencing(25%), allowed detection of mutant copies in a mixture 0.4% of DNA from BRAF positive cells with DNA from wild types. In classical PTCs, BRAFV600E was detected from formalin-fixed paraffin-embedded (FFPE) tissue specimens by dPCR in 24/30 (80%). BRAFV600E was not detected in follicular PTCs and other tumors. The BRAF mutation rate of ten classical PTC fine-needle aspiration (FNA) specimens were compared with their FFPE specimens. In 10 aspiration tissue samples, the BRAF mutation was detected in 7 samples (70%) by dPCR and 4 samples(40%) by CasPCR. In 10 FFPE samples, the BRAF mutation was detected in 7 samples (70%) by Roche real-time PCR and was completely matched the dPCR result for their aspiration specimens. The sensitivity and specificity of CasPCR for detecting the BRAF mutation was 57.1% and 100% in FNA samples.

Conclusions: Digital PCR could be a more sensitive method to direct Sanger sequencing and CasPCR for BRAF mutation detection of thyroid cancer. Accurate screening for BRAF mutation may contribute to improving the risk stratification of PTC.

OE-3 ASM, GRIP STRENGTH AND GAIT SPEED IN MENOPAUSAL WOMEN WITH TOTAL THYROIDECTOMY

1,2WEI-LUN WEN, 1,3,4,5SZU-CHIA CHEN, 1,2WEI -HAO HSU, 6HUI-CHUN YU, 6,7JUI-SHENG HSU, 6MING-CHEN SHIH, 2HE-JIUN JIANG, 2,4MEI-YUEH LEE

1Department of Internal Medicine, Kaohsiung Municipal Siaogang Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan; 2Division of Endocrinology and Metabolism, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan; 3Division of Nephrology, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan; 4Faculty of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan; 5Research Center for Environmental Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan; 6Department of Medical Imaging, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan; 7Department of Radiology , Faculty of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan

Background: There has been a growing attention toward sarcopenia not only in worldwide but also in Taiwan. There were several known risk factors including aging, malnutrition, diabetes and even some hormones and osteoporosis involved, but few published papers revealed relationship between thyroidectomy and sarcopenia. As post-thyroidectomy patients were majorly follow-up at our endocrine & metabolic outpatient department, we designed a study to analyze sarcopenia and its risk factors in this specific population.

Methods: This prospective, observational, cross-sectional, controlled study involved 50 postmenopausal women with regular visits to the Outpatient Department of Endocrinology and Metabolism, Kaohsiung Medical University Hospital (KMUH) for treatment and follow up after complete removal of thyroid, which included both benign and malignant neoplasms of thyroid on initial diagnosis. We measured their body composition including height-adjusted appendicular skeletal muscle mass (ASM/ht2) and bone mineral density(BMD) via Dual-energy X-ray Absorptiometry (DXA); we then also performed functional testing including handgrip strength and gait speed; Geriatric Nutritional Risk Index(GNRI), a nutrition surrogate marker was calculated by baseline serum albumin level and body weight, as follows: GNRI = [14.89×albumin (g/dL)] + [41.7×(body weight/ideal body weight)]; other comprehensive laboratory survey related to thyroid function, reproductive axis, and mineral metabolism were also collected. Multiple stepwise linear regression analysis was used to identify the factors associated with ASM/height2, handgrip strength and gait speed after multiple adjustments. A p value < 0.05 was considered to be statistically significant.

Results: In our study population, the prevalence of sarcopenia was 26%, defined by ASM/ ht2 ≤ 5.67 kg/m2 according to International Working Group on Sarcopenia (IWGS) criteria. The determinants of ASM/height2, handgrip strength, and gait speed using multivariable stepwise linear regression analysis were: Low GNRI, low femoral neck BMD, low TSH, and low thyroglobulin Ab for

low ASM/height2; long menopausal years and low ASM/height2 for low handgrip strength; young age, low GNRI, and high T3 for low gait speed.

Conclusions: Age, menopausal duration, BMD, GNRI, thyroid function, and thyroglobulin antibody were significantly associated with sarcopenia or lower functional capacities in menopausal women with total thyroidectomy.

OE-4 HYPERTHYROIDISM AND RISK OF SEIZURE: A NATIONAL POPULATION-BASED STUDY

1HAN-WEN LIU, 1,2TING-I LEE, 3BEN-CHANG SHIA

1Division of Endocrinology and Metabolism, Wan Fang Hospital, Taipei Medical University, Taipei, Taiwan; 2Department of General Medicine, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan; 3Research Center of Big Data, College of Management, Taipei Medical University, Taipei, Taiwan

Background: Dysfunction of central nervous system may occur in patients with hyperthyroidism. There are a few case reports of seizure attack in patients with hyperthyroidism. The underlying pathogenesis is not clear. A population-based cohort study was performed to analyze the incidence of seizure among hyperthyroidism patients.

Methods: Adult patients who had hyperthyroidism diagnosis and received either antithyroid drugs, thyroidectomy, or radioiodine therapy were identified from Taiwan National Health Insurance Research Database between 2000 to 2013. Patients with history of stroke, brain tumor, or head trauma were excluded. The main outcome was the occurrence of convulsion and epilepsy. The odds ratio (OR) was adjusted by multivariable Cox regression.

Results: 9272 patients were identified in the hyperthyroidism group and 27816 patients in control group. The incidence of convulsions was 0.6% in hyperthyroidism group and 0.4% in control group. Crude OR was 1.42 (95% confidence interval 1.04-1.94) and adjusted OR was 1.31 (95% CI 0.951.81). The incidence of epilepsy was 0.6% and 0.4% in each group. Crude OR was 1.42 (95% CI 1.031.97) and adjusted OR was 1.34 (95% CI 0.96-1.87).

Conclusions: The risk of seizure seems higher among hyperthyroidism patients. However, the OR was not significant after adjustment. Further research is warranted.

OE-5 LUNG CANCER WITH RADIOIODINE AVIDITY: A COHORT STUDY OF PATIENTS WITH THYROID CANCER

1YU-LING LU, 1SZU-TA CHEN, 2TSUNG-YING HO, 3WEN-HUI CHAN, 4CHUEN HSUEH, 1SHU-FU LIN

1Division of Endocrinology and Metabolism, Department of Internal Medicine, Chang-Gung Memorial Hospital, Taoyuan, Taiwan; 2Department of Nuclear Medicine, Chang-Gung Memorial Hospital, Taoyuan, Taiwan; 3Department of Medical Imaging and Intervention, Chang-Gung Memorial Hospital, Taoyuan, Taiwan; 4Department of Pathology, Chang-Gung Memorial Hospital, Taoyuan, Taiwan

Background: We evaluated, in a retrospective cohort, the incidence of lung cancer with radioiodine (RAI) avidity on whole-body scan and the potential mechanism driving RAI uptake.

Methods: The incidence of lung cancer with RAI avidity was assessed using our prospectively maintained database of patients with thyroid cancer at a medical center. Immunohistochemistry was performed to determine sodium/iodide symporter (NIS) expression in lung cancer specimens.

Results: A total of 4,602 patients with well-differentiated thyroid cancer (WDTC) diagnosed between December 1, 1976 and May 28, 2018 were identified in this database. Among them, 33 patients with papillary thyroid cancer developed lung cancer during follow up of WDTC. Nine of 33 patients exposed to Iodine-131 (131I) within one year prior to the diagnosis of lung cancer were further evaluated. One of 9 (11.1%) lung cancers demonstrated the ability to uptake 131I on RAI scan. Immunohistochemical staining of archived lung cancer specimens revealed NIS expression in 3 of 8 (37.5%) lung cancers. Of these, the one with RAI avidity had the highest level of NIS expression.

Conclusions: Our data reveal that a significant proportion of lung cancers have NIS expression. However, only lung cancer with high NIS expression demonstrates RAI avidity.

OE-6 IODINE SUPPLEMENTATION AND SOCIOENVIRONMENTAL INFLUENCES ON IODINE NUTRITION STATUS OF PREGNANT WOMEN IN TAIWAN

1FAN-FEN WANG,

2CHYI-HUEY BAI, 3KAM-TSUN TANG, 2YUN-CHU WANG, 3CHUN-JUI HUANG

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

Background: Iodine deficiency during pregnancy is associated with adverse obstetric outcomes and impaired fetal neurodevelopment. Iodine nutrition of pregnant women from different geographic areas and the impact of socioeconomic status have not previously been evaluated in Taiwan.

Methods: The current study is a substudy of Nutrition Survey of Pregnant Women in Taiwan 2017-2019. Multistage cluster sampling was performed based on geographical locations and hospital size. Spot urine was collected for urinary iodine analysis. Dietary iodine intake, including nutritional supplements, was assessed by food frequency questionnaire and 24-h food intake recall.

Results: A total of 1502 pregnant women with a mean age of 32.5 ± 4.8 years were enrolled, of whom 77 (5.1%) reported thyroid diseases. The weighted median urinary iodine concentration (MUIC) was 148 μg/L, indicating a borderline iodine insufficiency, and 149 μg/L if women with thyroid disease were excluded. Forty-nine brands of multivitamins were used by the studied population, 38 of which were intended for pregnant women. However, 15 (15/38) of these prenatal multivitamin brands did not contain iodine. The MUIC of pregnant women who used iodine-containing multivitamins was 167 μg/ L, which was significantly higher than that of those who didn’t use iodine-containing multivitamins (126 μg/L, p < 0.001). In the socioenvironmental analysis, lower MUIC was noted in women from the Eastern stratum, with lower educational level (senior high school or less), or lowest quintile of household income.

Conclusions: Socioenvironmental inequalities should be taken into account in the evaluation of a population’s iodine status and the development of strategies to achieve optimum iodine nutrition.