OE：Oral Presentation-Endocrine (1-6

OE-1 THE SYNERGISTIC EFFECT OF RENALASE AND CHRONIC KIDNEY DISEASE ON ENDOTHELIN-1 IN SUBJECTS WITH ESTABLISHED CORONARY ARTERY DISEASE ‒ A CROSS-SECTIONAL STUDY

1YU-HSUAN LI, 1WAYNE HUEY-HERNG SHEU, 1WEN-JANE LEE, 1CHIA-PO FU, 1KAE-WOEI LIANG, 1I-TE LEE

Division of Endocrinology and Metabolism, Department of Internal Medicine, Taichung Veterans General Hospital, Taichung City, Taiwan

Backgrounds. Endothelin-1 (ET-1), released from endothelium, is associated with endothelial dysfunction and vasoconstriction. Increased circulating ET-1 has been reported to be associated with long-term cardiovascular mortality. Renalase, released from kidney, metabolize catecholamines and regulate blood pressure. Increase in circulating renalase has been reported in the subjects with chronic kidney disease (CKD) and to be associated with coronary artery disease (CAD). We hypothesize a synergistic effect of serum renalase and CKD on serum ET-1 in the subjects with CAD. Methods. A total of 342 non-diabetic subjects with established CAD were included in this study. ET-1 and renalase were measured in all subjects after an over-night fasting. Results. The subjects with CKD had higher ET-1 (1.95 ± 0.77 vs. 1.62 ± 0.76 pg/mL, P < 0.001) and renalase (46.8 ± 17.1 vs. 33.9 ± 9.9 ng/mL, P < 0.001) than those without CKD. The subjects with both CKD and high renalase (> median of 36.2 ng/mL) showed highest serum ET-1 (P value for trend < 0.001). Using multivariate linear regression, high serum renalase with CKD is a significant risk for increase serum ET-1 (95%CI = 0.161‒0.645, P = 0.001). Conclusion. There is synergistic effect of high serum renalase and CKD on increase in ET-1 in the subjects with established CAD.

OE-2 TREATMENT EFFICACY AND SAFETY OF ULTRASOUND-GUIDED PERCUTANEOUS RADIOFREQUENCY ABLATION FOR BENIGN THYROID NODULES: KCGMH EXPERIENCE

1CHEN-KAI CHOU, 2SHENG-DEAN LUO, 2WEI-CHIH CHEN, 2YAN-YE SU, 3SHUN-YU CHI, 4WEI-CHE LIN

1Division of Endocrinology and Metabolism, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan; 2Department of Otolaryngology, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan; 3Departments of Surgery, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan; 4Department of Diagnostic Radiology, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan

OBJECTIVE: To evaluate the therapeutic efficacy and safety of ultrasound-guided percutaneous radiofrequency ablation (RFA) of benign thyroid nodules.

METHODS: From September 2016 to August 2017, we enrolled82patients (74 female, 8male, mean age 44.4 ± 12.3 years) with benign thyroid nodules for a single session of ultrasoundguided percutaneous RFA. The benign nature of all the nodules was confirmed by at least one- time ultrasound-guided core biopsy, and all the patients had normal thyroid functions. The symptomatic score, cosmetic scores and nodule volume of all the patients were recorded before treatment and during 1, 3 and 6 months follow-up.

RESULTS: The RFA procedures were completed with a mean time of 48.6 ± 24.2 min. The procedures were tolerated well in all the patients. Compared to the baseline condition, significant symptomatic and cosmetic score improvement was found in one month, 3 months and 6 months follow-up after RFA. Before RFA, the mean volume for thyroid nodules was 22.1 ± 21.5 cc. At the 1, 3 and 6-month follow-up, the nodule volume mean reduction ratios were 45%, 65% & 70%

CONCLUSION: Ultrasound-guided percutaneous RFA seems to be an effective and safe method for the treatment of benign thyroid nodules. It may gain a wide use in clinical practice.

OE-3 LOW-DOSE ADEFOVIR THERAPY RELATED OSTEOMALACIA MIMICKING MULTIPLE BONE METASTASIS - A CASE SERIES STUDY

1SHIH-PENG LIU, 2HAO-CHIH CHANG, 3YI-CHUN LIN

1 Taipei Veterans General Hospital; 2 Division of Cardiology, Department of Medicine, Taipei Veterans General Hospital; 3 Division of Endocrinology and Metabolism, Department of Medicine, Taipei Veterans General Hospital; 4Faculty of Medicine, National Yang-Ming University School of Medicine, Taipei, Taiwan

Low-dose adefovir induced osteomalacia is a rare drug adverse effect. It developed insidiously in patients with chronic hepatitis B treated with long term adevofir. As of 2017, no cases have been reported in Taiwan. In this study, we present three cases of low-dose adefovir therapy related osteomalacia, manifested with hypophospatemia and multiple bony fractures. The first case is a 66-year-old female presented with general bone pain and multiple fractures whose bone scan image showed multiple foci of increased uptake mimicked malignant metastasis. However, whole body PETCT reported no evidence of bone metastasis. She was a victim of choric hepatitis B and was taking antiviral therapy of adefovir 10 mg per day since April, 2008. Hyperphosphaturic hypophosphatemia with normal serum fibroblast growth factor-23 (FGF-23) level supported the diagnosis. Symptoms improved after cessation of adefovir and starting oral phosphate supplement. The second is a 76-yearold female with chornic hepatitis B and hepatoma s/p transarterial chemoembolization. She tooked adefovir 20 mg per day for 11 years who also manifested with hyperphosphaturic hypophosphatemia and general bone pain with multi-foci increased uptake on a bone scan image. The third patient is a 56year old male with chronic hepatitis B taking adefovir 10 mg per day for 10 years who sufferred from weight loss with general bone pain and bilateral femur fractures. Hyperphosphaturic hypophosphatemia was also noted while symptoms relieved after discontinuing adefovir and initiating oral phosphate supplement. Although it is rare, it is important that clinicians be aware of this uncommon adverse effect that developed insidiously after long-term adefovir therapy.

OE-4 A NOVEL MISSENSE MUTATION OF THE MEN1 GENE IN CHINESE FAMILY WITH MULTIPLE ENDOCRINE NEOPLASIA TYPE 1

1PO-CHIH LIANG, 1YI-HONG ZENG, 2CHEN-WANG CHANG, 1CHUN-CHUAN LEE, 3PAO-SHU WU, 4CHIA-CHI TSAI

1Division of Endocrinology and Metabolism, Department of Internal Medicine, MacKay Memorial Hospital and Mackay Medical College, Taipei, Taiwan; 2Division of Gastroenterology, Department of Internal Medicine, MacKay Memorial Hospital and Mackay Medical College, Taipei, Taiwan; 3Department of Pathology, MacKay Memorial Hospital and MacKay Medical College, Taipei, Taiwan 4Division of General surgery, Department of Surgery, MacKay Memorial Hospital and Mackay Medical College, Taipei, Taiwan

Background: Multiple endocrine neoplasia type 1 (MEN1) is an autosomal dominant disorder which associated with heterozygous germinal mutation of MEN1 tumor suppressor gene. It has a clinical picture of multiple neoplastic disease in at least two of the commonly affected organs : the parathyroid gland, pancreatic islets, pituitary, and adrenal cortex. MEN1 gene, which located on 11q13, comprising 10 exons and exon 2 through 10 encodes the 610-amino acid protein menin. We report a MEN1 case presenting with pancreatic, adrenal and pituitary tumor, who has a novel missense mutation. Case Report: A 54-year-old female with Type 2 DM, hypertension had received regular follow-up in our hospital. She had complaint of abdominal fullness seven years ago and abdominal ultrasound showed an anechoic lesion about 5.1mm in the pancreatic body. Abdominal computed tomography showed several subcentimeter low densities are found at pancreatic head and body. Tumor markers showed CA-199 (0.25 U/mL) and CEA (1.42 ng/mL). During follow-up with abdominal ultrasound, cyst was gradually increasing in abdominal computed tomography. Endoscopic Ultrasound (EUS) showed multiple anechoic to hypoechoic nodules in the pancreas, size up to 1.3 cm. Fine needle aspiration revealed pancreatic neuroendocrine tumor. In addition, she also had primary hyperparathyroidism, one pituitary microadenoma (5mm) with elevated prolactin(45.58 ng/ mL) and right adrenal non-functioning adenoma. Thus, MEN 1 was diagnosed. Patient then received total pancreatectomy and pathological report showing neuroendocrine tumors, grade 1. Exon-wide sequencing analysis of the MEN1 gene revealed a novel missense mutation at codon 1270 in exon 9, where a guanine residue was exchanged for cytosine (GAG > CAG) and, consequently, glutamic acid for glutamine (p.Glu424Gln; c.1270G > C). The same mutation was identified in her mother. We conclude that this mutation appeared to be responsible for MEN1 pathogenicity. Conclusion: Nowadays, a total of more than 1800 mutations were characterized. The incidence of neuroendocrine tumor (NET) has increased in the last four decades (from 1.09 to 5.25 per 100,000 individuals between 1973 and 2004) attributed to the improvement of diagnostic imaging, so clinicians should be aware of familial tumor syndrome. However, the lack of genotype-phenotype correlation results in difficulty for clinical investigation and mutational analysis in the diagnosis of MEN1. So we describe a novel missense mutation in the MEN1 gene that caused the MEN1 syndrome. 116

OE-5 EXPERIENCE OF IODINE-131 METAIODOBENZYLGUANIDINE THERAPY OF MALIGNANT PHEOCHROMOCYTOMA IN CCH

1SZU-HAN LIN, 1SHU-YI WANG

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

Pheochromocytomas are rare catecholamine-producing neuroendocrine tumors. Metastatic spread is the only true indicator of malignant behavior. Traditional treatments were debulking operation, chemotherapy with CVD regiment (CVD: cyclophosphamide,vincristine and dacarbazine) and/or Iodine-131 Metaiodobenzylguanidine (I-131 MIBG). Tyrosine kinase inhibitor or immunotherapyare ongoing treatment. In our case, a 43-year-old man was diagnosed pheochromocytomas in 2014 with initial presentation of diabetic poor control, intermittent headache, palpitation, sweating and high blood pressure. Abdominal CT revealed a 9.1*5.2cm mass over the right side suprarenal region with mild heterogeneous contrast medium enhance and liver invasion. Function survey showed elevated serum dopamine, nonepinephrine, epinephrine and urine VMA. He accepted adrenalectomy and liver sectomy with adjavant radiotherapy in 2014. However, under regular outpatient department follow, elevated serum nonepinephrine and urine VMA were mentioned. Abdominal CT showed para-aortic lymph node metastases. Malignancy pheochromocytomas was impressed. Chemotherapy CVD regimen and operation of lymph Node dissection were prescribed. However, condition was still progression. He accepted I131-MIBG 150 mCi IV infusion on 2016-11-09 in our hospital. Before the I131-MIBG treatment, patient need accepted lower dose I-131 whole body scan, which could predict treatment response. Patient need to management of excess catecholamines by alpha blockade and protect thyroid by lugol’s solution. Admitted on Day -1 for routine lab data survey and antiemetic ondansetron was prescribed for 3days. During I131-MIBG injection, be care of malignancy hypertension via frequency blood pressure monitor by patient himself. Hydration and frequent voiding were encourage and patient safely discharged on Day3. Follow up whole body scan at Day 7 and lab data showed no neutropenia or thrombocytopenia. Malignancy pheochromocytomas need treatment by multimodality, multidisciplinary and individualized approach. I131-MIBG treatment could be prescribed, but whole course was cost lot. Not only conventional systemic therapies, but some new tyrosine kinase inhibitors (ex. Sunitinib, Cabozantinib) or immune therapy (Pembrolizumab) were ongoing. Need further study in the future.

OE-6 GENETIC STUDY FOR COMBINED PITUITARY HORMONE DEFICIENCY IN TWO SIBLINGS

1WEI-LUN WEN, 2WEI-WEN HUNG, 3WEI-CHUN HUNG, 4YI-CHUN TSAI, 1CHIA-WEI LAI, 2PI-JUNG HSIAO, 4SHANG-JYH HWANG

1Department of Internal Medicine, Kaohsiung Medical University Chung-Ho Memorial Hospital, Taiwan, R.O.C; 2Division of Endocrinology and Metabolism, Department of Internal Medicine, Kaohsiung Medical University Chung-Ho Memorial Hospital, Taiwan, R.O.C; 3Department of Microbiology and Immunology, Kaohsiung Medical University, Taiwan, R.O.C; 4Division of Nephrology, Department of Internal Medicine, Kaohsiung Medical University Chung-Ho Memorial Hospital, Taiwan, R.O.C.

Background: In adults, hypopituitarism can occur in women after giving birth as in the case of postpartum hypopituitarism (PPHP). PPHP is associated with intrapartum or postpartum hemorrhage due to coagulation abnormality. Besides, combined pituitary hormone deficiency (CPHD) due to genetic factors can also lead to hypopituitarism, although the onset of CPHD in adulthood is rare. Here we reported hypopituitarism in two siblings and studied for the possible genetic etiology.

Case report and method: Of the two siblings, the younger sister, at the age of 31, was the first to visit our hospital due to failure of lactation after delivering her first baby by Caesarean section. Her pituitary function tests showed ACTH = 4.36pg/ml, cortisolT (upstream gene variant), c.59G > A (missense mutation) and c.109+3G >A (splice region variant). The last mutation, known to cause CPHD, alters the conserved region of intron 1, and is predicted to cause abnormal splicing of the transcription. In the remaining two genes POU1F1 and HESX1, no mutations were detected.

Discussion: We reported the two siblings diagnosed with postpartum hypopituitarism not related to any coagulation abnormality, but might be associated with genetic factors causing combined pituitary hormone deficiency. Further studies should be carried out in their family members without hypopituitarism to elucidate the mutation of PROP1 as the causative gene leading to hypopituitarism in the two siblings.