PE：Poster Presentation-Endocrine (1-29

PE-1 REPETITIVE SEIZURE AS THE INITIAL PRESENTATION IN A PATIENT WITH PSEUDOHYPOPARATHYROIDISM: A CASE REPORT

1NIEN-CHU YU, 1,2JIUN-LU LIN, 1,2CHUN-CHUAN LEE

1Division of Endocrinology and Metabolism, Department of Internal Medicine, Mackay Memorial Hospital, Taipei, Taiwan; 2Department of Medicine, Mackay Medical College, New Taipei City, Taiwan.

Background: Pseudohypoparathyroidism (PHP) is characteristic by the resistance to parathyroid hormone (PTH) and the resultant hypocalcemia.Albright’s hereditary osteodystrophy (AHO) is anapparent physical feature in patients with PHP-Ia. PHP-Ibpatientspresent predominant renal PTH resistance but lack any features of AHO. Most of PHP patients have defects in GNAS(20q13.3), an imprinted gene locus with multiple transcriptional units.We report one case with repetitive seizures and multiple brain calcification as the presentation of PHP.The patient has typical AHO feature but negative GNAS1 gene test.

Case Report: A 51 year-oldobese, short staturewoman got her body height fixed around 140cm since junior high school and jointspain easily when squatting since teenage. She received full denture due to severe calcification 20 years ago. She also has glaucoma. Her menstrual cycle duration was 4-5 days, interval 28 days, moderate amounts with some dysmenorrhea. She was pregnant three times but lost twice; intrauterine fetal death (IUFD) was diagnosed at her first and third fetus, but the second one grows well until now without any abnormality. She had hospitalization once for infection. Her first seizure was attacked and treated at Hualien Tzu-Chi Hospital since 20 years ago.Brain CT and MRI showed bilateral globus pallidus, bilateral head of caudate and bilateral cerebellar dentate nucleus calcification. Bilateral hands X-rays found shortening of bilateral 1st, 4th& 5th and left 3rd metacarpal bones and multiple phalangeal bones with bony exostosis. Lab data showed hypocalcemia, hyperphosphatemia, and elevated iPTH level.Subclinical hypothyroidism also noted. GNAS1 gene test was performed due to pseudohypoparathyroidism (PHP) was highly suspected. Now patient under regular Ca supply and OPD follow up Ca &P level.

Discussion: PHP is an idiopathic and inherited form of PTH resistance. Its characteristics are short stature, rounded face, foreshortened fourth and other metacarpals, obesity, and subcutaneous calcification. There are four types of PHP: type 1a, 1b, 1c, and 2. Diagnosis of PHP is defined by the coexistence of hypocalcemia, hyperphosphatemia with elevated PTH levels in the presence of normal Vitamin D value and normal renal function and the absence of hypercalciuria. GNAS1 locus mutation or imprinting abnormalities responsible for PHP different types. The goal of therapy should maintain serum total and ionized Ca level, oral Ca and Vitamin D supply, and prevent morbidity.

Conclusion: We present a case of repetitive seizure as the initial presentation in a patient with pseudohypoparathyroidism. The patient has classic metacarpals and phalanges abnormalities and symptomatic hypocalemia. The diagnosis of PHP requires physician’skeen insight.

PE-2 CATECHOLAMINE - INDUCED CARDIOMYOPATHY IN A 37 YEAR-OLD WOMAN WITH INITIAL PRESENTATION AS CARDIOGENIC SHOCK

1YU-PEI LIN, 2CHUN-YAO HUANG, 1CHEN LING HUANG, 4YI-JEN LAI, 1,3CHUNG-HUEI HSU

1Division of Endocrinology and Metabolism, Department of Internal Medicine, Taipei Medical University Hospital, Taipei, Taiwan; 2Division of Cardiology, Department of Internal Medicine, Taipei Medical University Hospital, Taipei, Taiwan; 3Department of Nuclear Medicine, Taipei Medical University Hospital, Taipei, Taiwan 4Department of Internal Medicine, Taipei Medical University Hospital, Taipei, Taiwan

Introduction Pheochromocytoma may present as non-specific symptoms that may cause loss of medical alertness initially. In fact, the possibility of excess amount of catecholamine release spontaneously or under stress may lead to severe cardiovascular events or related complications. Case Report The 37 y/o woman he was sent to ER due to sudden onset of palpitation. She also had chest tightness with headache. After admission cardiac echo revealed mild to moderate hypokinesis of LV anterior and apical wall with LVEF =47 %. Thallium scan also revealed no evidence of myocardial ischemia. The patient had mild proptosis and thyroid function showed free T4: 4.24 ng/dl, TSH < 0.05 uIU/ml, TRAb 41.2 % with thyroid echo compatible with Graves’ disease. Methimazloe 10 mg TID with propranolol 10 mg TID were given for treatment. In addition, 24 hr urine cathecholamine and VMA were checked due to recurrent palpitation with dyspnea. However, the patient asked to discharged then. After two weeks later she was sent to ER again due to palpitation with dyspnea. Her clinical condition get worsen with cold extremities and cyanosis appearance. HR was up to 160 bpm and CXR revealed pulmonary edema. Unstable hemodynamic status was noted then with desaturation and shock. CV doctor was consulted at ER and cardiac echo revealed severe generalized hypokinesis of LV with LVEF = 25 %. Lab data during last admission also revealed elevated 24 hr urine cathcholamine and VMA as: 24 hr urine Norepinephrine 2191.8 ug, 24 hr urine VMA 13.86 mg. CT was arranged at ER which also showed a 4.5cm well defined heterogenous enhanced mass arised from left side adrenal gland, suspected pheochromocytoma. Under the impression of (1) Cardiogenic shock suspected catecholamine-induced cardiomyopathy related (2) A mass over left adrenal gland suspected pheochromocytoma (3) Graves’ disease under treatment the patient was admitted for further workup and treatment. After admission CVS doctor was consulted for ECMO insertion due to cardiogenic shock. The patient had recovery of consciousness one day later. Repeat cardiac echo in the next morning also showed improved LV contractility. ECMO was weaned after 40 hrs and medication as Doxazosin 1mg BID with Propranolol 10 mg QID given for treatment. The patient also had extubation then due to improved condition. With the impression of pheochromocytoma., urologist was consulted for op evaluation. The patient received left laparoscopic adrenalectomy and the pathology

revealed pheochoromocytoma. Cardiac echo follow-up at OPD revealed normal LV chamber size with improving LV anterior wall motion. Conclusion : Patients with a cardiomyopathy, of non-specific origin, should ruled out pheochromocytoma. Catecholamines, especially norepinephrine, can cause a direct toxic effect on the myocardium just like the case above. The mechanism include increased concentration of calcium in the sarcoplasma and increased oxygen demand that induce cardiomyopathy with myocardial necrosis. However, the diagnosis of pheochromocytoma requires high clinical alertness due to variable clinical manifestations. In conclusion, early recognition of catecholamineinduced cardiomyopathy is important for patient with pheochromocytoma to minimize morbidity and mortality rate.

PE-3 HYPOTHYROIDISM WITH HIGH LEVEL OF FT4

1HELEN WEI, 1,2CHUN-LAN CHEN, 1,3CHING-CHIEH SU

1Internal medicine, Cardinal Tien hospital; 2Division of Laboratory, Cardinal Tien hospital; 3Division of endocrinology and metabolism, internal medicine, Cardinal hospital. School of medicine and Graduate Institute of Applied Science and Engineering, Fu-Jen Catholic University

59 years old woman came to endocrinology OPD with compliant of goiter for more than one year. Physical examination revealed diffuse goiter with nodular surface and rubbery firm in texture. Thyroid ultrasound showed diffused goiter with severely heterogeneous hypoechogenicity. Lab test reported free T4 (FT4) 2.08 ng/dl (0.7-1.9), TSH 114.596 mIU/L, anti-thyroglobulin antibody > 2500 (< 60) and thyroperoxidase antibody (TPOAb) >13000 (< 60). Syndrome of inappropriate secretion of TSH (SITSH) or thyrotoxicosis was considered as differential diagnosis. Low dose eltroxin (50 ug/ day) was given initially under the impression of hypothyroidism with unknown cause of high FT4. Two months later, blood test reported FT4 2.61, T3 109.81ng/dl (80-180) with lower TSH 14.049 and weakly positive TSH receptor antibody 19% (< 10%). Clinical symptoms improved with smaller size of goiter. Eltroxin was added to 500 ug once a week. Follow up two months later, thyroid functional tests reported FT4 3.71, T3 113.91 and TSH 12.753. Eltroxin dosage was increase to 600ug weekly. The 2-month follow up lab disclosed FT4 4.44, T4 11.3 ug/dl (4.6-12).

PE-4 UNDERWEIGHT INCREASES THE RISK OF EARLY DEATH IN TUBERCULOSIS PATIENTS: A POPULATION-BASED STUDY

1YUNG-FENG YEN, 2FU-I TUNG, 3YUN-JU LAI

1Section of Infectious Diseases, Taipei City Hospital, Taipei, Taiwan; 2Section of Orthopedics, Taipei City Hospital, Taipei City Government, Taipei, Taiwan; 3Division of Endocrinology and Metabolism, Department of Internal Medicine, Puli Branch of Taichung Veterans General Hospital, Nantou, Taiwan

Background: Evidence regarding the association between body mass index (BMI) and mortality in tuberculosis (TB) patients is limited and inconsistent. We investigated the impact of BMI on TB-specific and non-TB-specific mortality with respect to different timing of death. Material and method: All Taiwanese adults with TB in Taipei were included in a retrospective cohort study in 2012–2014. Multinomial Cox proportional hazards regression was used to evaluate the associations between BMI, cause-specific mortality, and timing of death. Results: Of 2,410 eligible patients, 86.0% (2061) were successfully treated, and TB-specific and non-TB-specific mortality occurred for 2.2% (54) and 13.9% (335), respectively. After controlling for potential confounders, underweight was significantly associated with a higher risk of all-cause mortality [adjusted hazard ratio (AHR), 1.57; 95% confidence interval (CI), 1.26–1.95], while overweight was not. When cause-specific death was considered, underweight was associated with an increased risk of either TB-specific (AHR, 1.87; 95% CI, 1.04-3.37) or non-TB-specific death (AHR, 1.52; 95% CI, 1.19-1.94) during treatment. With joint consideration of cause-specific and timing of death, underweight only significantly increased the risk of TB-specific (AHR, 2.25; 95% CI, 1.09–4.63) and non-TB-specific mortality (AHR, 1.81; 95% CI, 1.29–2.55) within the first 8 weeks of treatment. Conclusion: This study suggests that underweight increases the risk of early death in TB patients during treatment.

PE-5 A VERY RARE CASE OF PULMONARY LYMPHANGITIC CARCINOMATOSIS IN PATIENT WITH RECURRENT PAPILLARY THYROID CARCINOMA

TSE-YING HUANG

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

Papillary thyroid carcinoma (PTC) has been defined as a malignant epithelial tumor showing evidence of follicular cell differentiation. Lung metastases are more frequent in young patients with PTC, and the lung is almost the only site of distant spread in children. Here we present a very rare case of pulmonary lymphangitic carcinomatosis in a 69-year-old man with recurrent papillary thyroid carcinoma. He had initial presentation with painless mass over left supraclavicular fossa, papillary thyroid carcinoma was then diagnosed and he received total thyroidectomy and lymph nodes dissection, with I-131 30mCi was prescribed initially after the first surgical intervention. Four years later, local recurrence was noted and lymph nodes dissection was carried out, without further adjuvant anti-cancer treatment. Two years later, severe cough with blood-tinged sputum developed. The follow up computed tomography (CT) showed recurrent tumor with pulmonary lymphangitic carcinomatosis.

PE-6 PITUITARY PLURIHORMONAL ADENOMA SECRETING TSH AND LH –A CASE REPORT

1YU-YI LIN, 1CHII-MIN HWU, 2WEI-HSIN WANG, 3YU-HUEI LI, 4TZONG-YOE LAI

1 Section of Endocrinology and Metabolism, Department of Internal Medicine,Taipei Veterans General Hospital, Taiwan; 2 Section of Neurosurgery, Department of Surgery, Taipei Veterans General Hospital, Taiwan; 3 Division of Endocrinology and Metabolism, Department of Internal Medicine, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan, ROC; 4 Lai’s clinic, Hua-Lien, Taiwan

Background. TSH (Thyrotropin) secreting pituitary adenoma (TSHoma) account for less than 1% of all causes of hyperthyroidism and 1% of all functioning pituitary tumors. Definite diagnosis and treatment of TSHoma are clinical challenge in practice. We report laboratory data, imaging findings, endocrine dynamic test, and treatment outcomes in a 50-year-old Taiwanese man with pituitary adenoma secreting TSH and LH. Case presentation. The patient was initially diagnosed and treated as goiter with primary hyperthyroidism and diabetes mellitus by general clinic doctor in 2014. He received anti-thyroid drug and oral hypoglycemic agent. Two years later, he visited to Endocrinologist’s clinic for poor glycemic control. Central hyperthyroidism was diagnosed due to measurable TSH level in the prescence of increased serum thyroid hormone level. Sella MRI revealed left sided pituitary lesion. He was referred to Taipei Veteran General Hospital for further management. There was no family history of thyroid disease. Physical examination was not remarkable except diffuse grade 3 goiter and tachycardia (heart rate: 100~115 beat per minute). Laboratory data showed TSH 4.89 uIU/ml, free T4: 3.05 ng/dl, T4: 16.02 μg/dl, T3: 249 ng/dl, free T3: 8.0 pg/ml, normal range of thyroid autoantibodies. Two times of TRH stimulation test showed blunted TSH response. Pituitary hormones level were within normal limit except mild elevation of testosterone 12.69 ng/ml. Sella MRI showed macroadenoma (size 10x10x7.6 mm) at left pituitary gland. Thyroid sonography revealed heterogenous echogenicity with increased size and vascularity of both lobes. I-131 uptake was homogenous uptake (94%). Surgery was performed after one year of definite diagnosis due to personal reason. TSH level returned to normal ranges (0.799 uIU/ml) in 1st post operative day. Histologically, the pituitary mass was compatible with plurihormonal adenoma and immunohistochemistry showed positivity for TSH (4+) and LH (3+). Antithyroid agents were discontinued and good glycemic control was noted after operation. Conclusion. A biochemical hallmark of TSHoma is an escape of TSH from the feedback loop that is detectable TSH levels in the prescence of increased serum thyroid hormone level. Diagnosis of TSHoma was frequently unrecognized and thus much delayed despite its relatively straightforward. Physician should keep in mind that the importance interpretation of simple laboratory tests to avoid delay diagnosis and unnessary treatments.

PE-7 PARATHYROID ADENOMA PRESENTED WITH HYPOCALCEMIA IN A PATIENT WITHOUT CHRONIC RENAL INSUFFICIENCY

1HSUAN-WEI LIN, 1,2CHIN-SUNG KUO

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

Elevated serum parathyroid hormone level together with hypocalcemia usually suggests secondary hyperparathyroidism. Parathyroid adenoma commonly co-exists with hypercalcemia, or with normocalcemia in some case reports. We report a case of parathyroid adenoma associated with hypocalcemia in a patient without chronic renal insufficiency. The patient was successfully treated by left inferior parathyroidectomy that was preceded and followed by intensive calcium and vitamin D supplementation. To our knowledge, there is only one previously reported case of parathyroid adenoma associated with hypocalcemia and metabolic bone disease in a patient with chronic kidney disease.

PE-8 THYROID MUCOSA-ASSOCIATED LYMPHOID TISSUE LYMPHOMA IN A 63-YEAR-OLD WOMAN: A CASE REPORT

1HSIN-WEI WANG, 1EDY KORNELIUS, 1YI-SUN YANG, 1SHIH-CHANG LO, 1CHIENNING HUANG

1Division of Endocrinology and Metabolism, Department of Internal Medicine, Chung Shan Medical University Hospital, Taichung, Taiwan, R.O.C

Introduction: Primary thyroid lymphoma is rare but still a possible differential diagnosis of thyroid nodule. The major symptom is a rapid growing thyroid nodule. Preexisting autoimmune thyroiditis is a known risk factor. We report a case with thyroid mucosa-associated lymphoid tissue lymphoma (MALT lymphoma) Case: A 63-year-old female suffered from a progressive growing nodule over pre-trachea area in recent 3 months. Physical examination showed a painless, movable, and hard nodule over pre-trachea area. She had history of Hashimoto’s thyroiditis, and thyroid function was euthyroid status under Eltroxin treatment. Thyroid echo showed a 19.0 x 15.9 x 6.6 mm regular hypoechoic nodule over isthmus area. Fine needle aspiration showed atypical cell and polymorphous lymphocytes. Isthmusectomy was arranged by the surgeon and pathology revealed architectural effacement by monocytoid atypical lymphocytes. Mucosa-associated lymphoid tissue lymphoma was diagnosed. Further tumor survey with Positron Emission Tomography showed no residual tumor or distal metastasis. Ann Arbor staging was stage IE (Extranodal). Panendoscopy was arranged which revealed acute gastric ulcer and gastroesophageal reflux disease. Test for Helicobacter pylori infection showed positive. No gastric MALT lymphoma was found. Hematologist was consulted for further treatment, and gastric Helicobacter pylori eradication was suggested followed by chemotherapy or closely monitor.

PE-9 131I ABLATION THERAPY IN PATIENT WITH THYROID CANCER AND ESRD ON HEMODIALYSIS: CASE REPORT

1CHIH-JEN WANG, 1SHU-YI WANG

1Division of Endocrinology and Metabolism, Department of Internal Medicine, Changhua Christian Hospital, Taiwan, R.O.C

Radioiodine ablation (131I) is primarily administered postoperatively as a ablation or adjuvant treatment after thyroidectomy for well differentiated thyroid cancers. 131I dosage recommendation and benefits of postoperative RAI administration are different according to the three American Thyroid Association (ATA) risk categories (low, low-to-intermediate and high risk). For a patient with a normal renal function, iodine is mainly eliminated by the kidney, and majority of iodine is absorbed by the thyroid gland. Therefore, the administered dosage of 131I and the timing of hemodialysis are critical issues in a patient with end-stage renal disease (ESRD) on hemodialysis. Here we presents a case with thyroid papillary carcinoma and ESRD on hemodialysis, who received approximately 50% of a typical empirical dose of 131I for a patient with ATA low-to-intermediate risk. From the review of previous literatures, few publications have prescribed the recommendations for management of thyroid cancer in patients with ESRD. Therefore, we focused on three important questions in patients with ESRD on hemodialysis, including: (1) recommendation of modified 131I dose; (2) when to perform hemodialysis after the 131I administration in order to maximize treatment benefit while minimizing the risk to the patient and the treating medical personnel; and (3) safety concerns regarding radioiodine activity during hemodialysis. In this paper, we will review previous literatures concerning these critical questions, and we hope to share our management experience and literature review may help other clinical physicians to face the similar clinical scenario in future.

PE-10 BILATERAL ADRENAL GLAND HEMORRHAGE: A CASE REPORT AND REVIEW OF THE LITERATURE

1YUNG-NIEN CHEN, 1CHEN-KAI CHOU, 1JUNG-FU CHEN, 2HAN-MING LAI

1Division of Endocrinology and Metabolism, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital, Taiwan, R.O.C.; 2Division of Rheumatology, Allergy and Immunology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital, Taiwan, R.O.C.

Background. Adrenal hemorrhage is an uncommon condition with variable presentation that may lead to acute adrenal crisis, shock and mortality. Methods. We report clinical features and imaging findings of a middle-aged female with acute bilateral adrenal gland hemorrhage. Results. A 66-year-old woman presented with a 1-week history of epigastric pain. Eosinophilia was noted and computerized tomography of abdomen showed bilateral adrenal hemorrhage and mesenteric vasculitis, suspect autoimmune disease related. The raised titers of anti-beta2 GPI and anti-cardiolipin IgG antibodies were considered to strongly suggest an underlying diagnosis of the antiphospholipid syndrome. Elevated serum IgG4 was also noted. The patient’s symptoms of adrenal failure resolved after administration of intravenous corticosteroids in an appropriate dose and eventually discharged home. Conclusion. Adrenal hemorrhage is a rare condition and may be associated with stress, sepsis and autoimmune diseases. Bilateral adrenal hemorrhage commonly leads to acute adrenal insufficiency, adrenal crisis, and death, unless it is recognized and treated promptly.

PE-11 DECIPHERING THE REGULATORY CODE OF THE RELATIONSHIP BETWEEN THE CHOLINE TRIMETHYLAMINE LYASE (CUTC) AND CARDIOVASCULAR DISEASES

1MING-CHAN LEE, 2YEH CHEN, 3SHIH-TING TSENG

1Department of Nephrology, Da-Chien General Hospital; 2Department of Department of Biotechnology, Hungkuang University; 3Department of Metabolism and Endocrinology, Kuang-Tien General Hospital

Cardiovascular disease (CVD) is composed of numerous heart and vessel problems, especially a process called atherosclerosis. In our dietary intake, like choline, phosphatidylcholine (PC), carnitine, can be converted to trimethylamine (TMA) by some unique gut microbiota. The generation of TMA is followed by the production of trimethylamine N-oxide (TMAO) converted by host flavin-containing monooxygenase 3 (FMO3). Eventually, the elevated TMAO are associated with atherosclerosis and cause the cardiovascular disease. In this project, we had focused on the gut-bacterial enzyme named Choline/TMO-lyase CutC, which is a key enzyme involved in the choline-TMA conversion pathway. To dissect the CutC enzyme, we had designed a series of the in vitro experiments, that is, the expression and purification of the recombinant CutC enzyme. This project will lay a foundation of unraveling the biological function of CutC and the therapeutic design of gut-microbiota-target enzyme based on the structural biology.

PE-12 LONG-TERM THERAPEUTIC OUTCOME OF PAPILLARY THYROID CARCINOMA WITH HYPERPARATHYROIDISM: A CASE-CONTROL STUDY

1CHIH-YIU TSAI, 1SZU-TAH CHEN, 2CHUEN HSUEH, 3YANN-SHENG LIN, 1JEN-DER LIN

1Division of Endocrinology and Metabolism, Department of Internal Medicine, Chang Gung Memorial Hospital, Chang Gung University, Taiwan, R.O.C.; 2Department of Pathology, Chang Gung Memorial Hospital, Taiwan, R.O.C.; 3Department of General Surgery, Chang Gung Memorial Hospital, Taiwan, R.O.C.

Objective. This study is aimed to evaluate the long term prognosis of papillary thyroid carcinoma patients with hyperparathyroidism following multimodality treatment. Subjects and methods. We performed a case-control study from a thyroid cancer database of a medical center prospective collected during 1980 to 2013. The study cohort was patients with concomitant papillary thyroid carcinoma and hyperparathyroidism. Patient matching with propensity score method was conducted for enrollment of control group who had no hyperparathyroidism. The treatment outcomes of cancer were compared. Result. A total of 27 study subjects were identified from 4,062 consecutive thyroid cancer patients. There were 10 primary and 17 renal hyperparathyroidism. We found 3 disease nonremission and 4 mortality events in the study cohort during a mean 7.7 years of follow-up. The risk of non-remission showed no difference compared with control group but the overall mortality was significantly increased (hazard ratio = 4.43 [95% confidence interval = 1.11 – 17.75], P value = 0.035). All mortality was non-thyroid cancer related, including two cardiovascular events with in-hospital deaths. Conclusion. Papillary thyroid carcinoma patients with hyperparathyroidism were usually diagnosed in early stages with compatible therapeutic outcomes. However, the effect of underlying comorbidity should be carefully evaluated.

PE-13 CASE REPORT: HYPERTROPHIC OSTEOARTHROPATHY IN 21 YEARS OLD YOUNG MAN

1WEI-LIN CHEN, 1CHIA-PO FU, 1I-TE LEE

The Division of Endocrinology and Metabolism, Department of Internal medicine, Taichung Veterans General Hospital, Taiwan, R.O.C.

Hypertrophic osteoarthropathy presents either thickened scalp, clubbing digits or both. The primary type is a rare genetic disorder resulted by failure of prostaglandin metabolism. We present a case with incomplete type primary hypertrophic osteoarthropathy.

PE-14 ACROMESOMELIC DYSPLASIA MAROTEAUX TYPE WITH VITAMIN D DEFICIENCY -A CASE REPORT

1,3YU-YI LIN, 1HONG-DA LIN, 1HARN-SHEN CHEN, 2DAU-MING NIU, 3KUANG-KUO WANG

1Section of Endocrinology and Metabolism, Department of Internal Medicine, Taipei Veterans General Hospital, Taiwan; 2Department of Pediatrics, Taipei Veterans General Hospital, Taiwan; 3Department of Medicine, Cheng Hsin General Hospital, Taipei, Taiwan

Background. Acromesomelic dysplasia Maroteaux type (AMDM) is an extremely rare autosomal recessive osteochondrodysplasia belonging to the group of acromesomelic dysplasia and first described in 1971 by P. Maroteaux. It is caused by mutations in the NPR2 (neuropilin 2) gene located on chromosome 9p21-p12 which encoding the natriuretic peptide receptor B( NPR-B). NPR-B acts as the transmembrane receptor for cartilage natriuretic peptide (CNP). Both CNP and NPR-B are important for regulation of longitudinal growth. Clinical features are severe dwarfism with height below 120 cm, shortening of middle and distal segment of limbs, dolichocephalic skull with shortness of the trunk, reduced vertebral height without any associated facial or mental abnormalities. Radiological features showed short broad fingers, shortening of long bones with bowed radius, and vertebral abnormalities. We report laboratory data and imaging findings of a 40-year-old Taiwanese woman with typical acromesomelic dysplasia Maroteaux type. Case presentation. A 40-year old woman visited to our endocrine clinic due to painless goiter for one week. Due to specific general appearance, detail history taking and physical examination were done. Her parents are close relative marriage (consanguinity). Patient was married with delivered one normal appearance child in 2012. Pre-pregnancy screening of the patient revealed grossly unremarkable uterus, ovaries, and fallopian tubes. Her body height was 123 cm, body weight was 32 kg and BMI was 21.15. General examination revealed short stature with specific fingers pattern. Clear mentality without neurological deficit were found. Thyroid nodule work-up showed cystic fluid only. Endocrine hormonal studies were within normal limits except low vitamin-D level (25-OH Vit-D: 19.99 ng/ml). Bilateral forearm and hands x-rays (Figure:1~2) showed short metacarpal and phalangeal bones, pointing appearance of distal ulna. Tripple film of spine (Figure:3) showed no significant evidence of scoliosis more than ten degree in Cobb’s angle. Bone mineral density of L-spine (Figure: 4) showed osteopenia (T-score: -1.0~-1.6). She was clinically diagnosed as acromesomelic dysplasia, Maroteaux type (AMDM) due to consanguinity marriage with specific x-rays findings. Conclusion Acromesomelic dysplasia Maroteaux type is a rare, inherited, skeletal disorder that results in a particular form of short stature, acromelia and mesomelia. World literature described around 40 to 50 cases of AMDM till now. Genetic counseling is of benefit for affected individuals and their families. As genetic evaluation was not possible in all these patients, AMDM was diagnosed on clinical ground.

PE-15 HUGE PARATHYROID MASS WITH HYPERCALCEMIC CRISIS: A CASE REPORT

1PAO-LUNG HSIEH, 1WEI-FU HUANG, 1PO-CHENG CHEN, 1KAI-JEN TIEN, 1NAICHENG YEH, 1SHANG-GYU LEE, 1CHWEN-YI YANG

1Division of Endocrinology and Metabolism, Department of Internal Medicine, Chi Mei Medical Center, Tainan, Taiwan

Background: Hypercalcemic crisis represents a life-threatening emergency. The most common cause is hypercalcemia of malignancy. Previous undetected primary hyperparathyroidism, medicationinduced hypercalcemia, and a few rarer causes may result in this endocrine emergency as well. Primary hyperparathyroidism is a disorder of one or more of the parathyroid glands. Mostly caused by solitary parathyroid adenoma (85%). Parathyroid adenocarcinoma is even rare (< 1 %).

Material and Methods: A 47 years old lady went to our rheumatology OPD due to general soreness for 2 months, and lab data showed hypercalcemia (serum Ca 16.2 mg/dL) and high iPTH (1453 pg/mL). After admission to our Meta ward, thyroid echo showed a lobulated heterogeneous hypoechoic mass inferior to left thyroid gland, about 4.6x3.5cm, with esophagus deviation to right side, suspicious of parathyroid origin. Sella MRI revealed a 3 mm pituitary microadenoma. Pancreatitis and peptic ulcer disease were also diagnosed. Serum level of Gastrin, Chromogranin A and calcitonin were checked. For r/o MEN 1, pancreas MRI was performed, but no definite lesion was detected. We persuaded the patient to check MEN gene, but she refused. Parathyroid scan and bone scan were arranged and it showed bilateral high intake at lower thyroid lesion.

Results: Subtotal parathyroidectomy was performed. Four normal size of parathyroid glands and one huge mass was seen. Left lower parathyroid gland and this huge mass were removed. However, high iPTH and hypercalcemia persisted. Following chest CT showed a suspicious tumor lesion or hematoma at superior mediastinum. Pathology revealed atypical parathyroid cell for that huge mass and normal parathyroid cell for left lower parathyroid gland.

Conclusion: Primary hyperparathyroidism is rarely due to parathyroid adenocarcinoma or MEN. This unusual case showed atypical parathyroid cell and pituitary microadenoma. Moreover, it is unusual that high iPTH and hypercalcemia persisted after Subtotal parathyroidectomy. Further study and management still be needed.

PE-16 LITHIUM-INDUCED HYPOTHYROIDISM: A CASE REPORT

1CHIN-CHOU YANG

1Tsaotun Psychiatric Center, Ministry of Health and Welfare

Abstract: Lithium is widely used as a mood stabilizer in managing mental illness, mainly mania and bipolar disorder. In this article, we report a 38 years old woman admitted for mania. Lithiuminduced hypothyroidism was found. It is strongly recommended to evaluate thyroid function before starting to treat psychic patients with Lithium. If hypothyroidism develops, treatment should be carried out according to guidelines, and it does not require withdrawal of lithium.

Case report: A 38 years old woman without systemic disease was admitted to our psychiatric ward in May 2016, under the diagnosis of mania disorder. The routine laboratory study revealed normal thyroid function at first. (TSH: 2.56 uIU/ml, FT4: 0.66 ng/dl) Her medication included Carbamazepine, Estazolam, Trihexyphenidyl, Haloperidol, and Lithium. In September 2017, abnormal thyroid function was found. (TSH < 0 uIU/ml, FT4 1.18 ng/dl) On January 2018, we rechecked thyroid function again, together with adrenal function and thyroid antibodies. The data revealed: TSH 17.39 uIU/ml, FT4 0.32 ng/dl, T3 0.77 ng/ml, AM Cortisol 10.19 ug/dl, TSHR Ab 9%, Anti-TPO Ab > 13000 IU/mL. The tentative diagnosis was Lithium-induced hypothyroidism. Levothyroxine was prescribed for hypothyroidism treatment.

Discussion: The thyroid axis is prone to interactions with many drugs, and hypothyroidism is the most common condition of drug-induced thyroid dysfunction (1). Drugs can induce hypothyroidism through different mechanisms, including inhibition of synthesis and/or release of thyroid hormones, inhibition of TSH synthesis, and other immune mechanisms. Lithium is the first-line treatment for bipolar disorder. However, it can cause hypothyroidism by inhibition of thyroid hormone secretion (2,3). Besides, it can also cause goiter and hyperthyroidism (4,5). The prevalence of hypothyroidism induced by Lithium ranged from 6 to 52 percent according to several series (1), and it usually occurs during the first two years of lithium therapy (3). When hypothyroidism develops, it should be treated with thyroxin according to guidelines. Usually, there is no need to discontinue Lithium treatment, especially without consultation with the patient’s psychiatrist first.

References:

1. RIZZO, Leonardo FL; MANA, Daniela L.; SERRA, Héctor A. Drug-induced hypothyroidism. Medicina (Buenos Aires), 2017, 77.5: 394-404. 2. MCKNIGHT, Rebecca F., et al. Lithium toxicity profile: a systematic review and metaanalysis. The Lancet, 2012, 379.9817: 721-728. 3. LAZARUS, John H. Lithium and thyroid. Best practice & research Clinical endocrinology & metabolism, 2009, 23.6: 723-733.

4. BARCLAY, Murray L., et al. Lithium associated thyrotoxicosis: a report of 14 cases, with statistical analysis of incidence. Clinical endocrinology, 1994, 40.6: 759-764. 5. MILLER, Karen K.; DANIELS, Gilbert H. Association between lithium use and thyrotoxicosis caused by silent thyroiditis. Clinical endocrinology, 2001, 55.4: 501-508.

PE-17 COMPUTER-AIDED DIAGNOSTIC TECHNIQUE IN FDG POSITIVE THYROID NODULE– A CLINICAL EXPERIENCE OF 73 NON-THYROID CANCER PATIENTS

1YI-HSUAN LIN, 1SZU-TAH CHEN

1Division of Endocrinology and Metabolism, Department of Internal Medicine, Chang Gung Memorial Hospital, Chang Gung University, Taiwan, R.O.C.

Aim: The aim of this study was to characterize ultrasonography (US) features by a computeraided diagnosis (CAD) technique together with PET characters of 18-FDG-avid benign thyroid nodules to help clinical decision making.

Patients: From August 2008 to October 2016, a total of 81 incidentally found FDG-avid thyroid nodules were found in 73 non-thyroid cancer patients (32 males and 41 females, aged from 38.7 to 84.6 years) at Chang-Gung memorial hospital (CGMH). Another 38 non-FDG-avid nodules were found in these patients after US examination. Eventually16 of these patient received thyroidectomy.

Diagnosis: US were retrospectively analyzed by expert endocrinologists according to the Thyroid Image Reporting and Data System (TIRADS) and the CAD software (AmCAD-UT; AmCad BioMed, Taiwan), respectively. The CAD parameters include anechoic area, hyper- and hypo- echogenicity, heterogeneity, margin, taller than wide, eccentric area and the lesion size was measured at the greatest dimension of the nodule. The final diagnosis was confirmed by either FNA cytology and/or pathological report. 45 benign, 5 indeterminate and 19 (8 thyroid and 11 metastatic) malignant lesions were reported in 69 FDG avid nodules by FNA or operation. In contrast, 16 benign, 1 indeterminate and 1 thyroid cancer were reported in 18 non-FDG-avid nodules by FNA.

Result: No significant difference of lesion size or individual CAD parameters was found between benign, indeterminate and malignant groups in FDG-avid nodules. Linear regression was then applied to correlate the CAD parameter with the standardized uptake value (SUV) in FDG-avid nodules, which showed one-unit elevation of SUV decreased 0.48 units of eccentric area value (p < 0.05). A taller than wide CAD character was found significantly different between thyroid originated cancer and metastatic lesions (0.30 vs 0.16, P < 0.05). In patients with simultaneous FDG-avid and non-avid nodules, a larger size (2.21 vs 1.68, p < 0.05) was found in the FDG-avid nodules without significant difference among CAD parameters and TIRADS score. To determine the cut-off value of the CAD parameters, 0-7 points were given for the sum-up of each parameter positive for malignant tendency. The best discrimination point for the prediction of malignancy was 1 with a sensitivity of 100% and a specificity of 33.3%. The area under the ROC curve (AUC) was 0.657 with 95% confidence interval (95% CI) within 0.544-0.759; p < 0.05. The AUC increased to 0.728 with 95% CI within 0.618-0.821 and a 0.0705 difference between areas, p < 0.05 when the PET score was combined.

Conclusion: We concluded that FDG-avid thyroid nodules with irregular shape of solid component and greater than 15% cystic part may represent benign nodules. Moreover, PET improves the diagnosis of thyroid malignancy by AmCAD.

PE-18 PARAGANGLIOMA AT CAROTID BIFURCATION PRESENTING AS CAROTID BODY TUMOR, COEXISTENCE WITH PAPILLARY THYROID CARCINOMA: A DIAGNOSIS DILEMMA

1FAN CHOU, 1CHIH-YUAN WANG

1Division of Endocrinology and Metabolism, Department of Internal Medicine, National Taiwan University Hospital, Taiwan, ROC.

PURPOSE To establish the difficulty of differentiating the neck mass between carotid body paraganglioma and recurrent papillary thyroid carcinoma.

METHOD We present a case report of a 66-year-old woman with previous history of papillary thyroid carcinoma, presumed a left carotid body tumor, as was expected from clinical and MRI findings.

RESULT Repeated cytology examination showed carcinoma, metastasis. Lab revealed normal thyroid function, low level of thyroglobulin, and the patient had no sign of malignancy. Biopsy examination revealed non-functional paraganglioma at carotid bifurcation.

CONCLUSION Carotid body tumors are rare tumors but highly related with neck paraganglioma, which mostly benign tumor, might related with germline of SDHx, SDHAF2, MAX and TMEM127 mutations. Differential diagnosis is crucial not only for planning surgery, but also for the postoperative treatment. The vascular structure and relationship with the adjacent vascular structures of the tumor should be detected by noninvasive diagnostic methods such as MRI and magnetic resonance angiography. Thus, surgical complications can be significantly reduced. Radiotherapy is recommend for giant and recurrent carotid body paragangliomas, advanced and unresectable, multiple tumors, and with malignant carotid body paragangliomas metastatic to the regional lymph nodes.

PE-19 GRAVES’ DISEASE COMPLICATED WITH HASHIMOTO ENCEPHALOPATHY: A CASE REPORT AND REVIEW OF LITERATURE

1SHIH-CHE HUA, 2CHIEN-CHUNG CHEN

1Division of Endocrinology and Metabolism, Department of Internal Medicine, St. Martin De Porres Hospital, Taiwan.; 2Division of Neurology, Department of Internal Medicine, St. Martin De Porres Hospital, Taiwan.

Hashimoto encephalopathy (HE) is known as a steroid-responsive encephalopathy associated with high titers of antithyroid antibodies. The prevalence is rare and estimated to be 2.1/100 000 subjects. HE is predominantly diagnosed in the adult population and the mean age is around fifty. We reported a pediatric case of Graves’ disease complicated with HE. A 15-year-old girl was brought by her parents to visit our endocrine clinic because of weight loss of 8 kg, behavioral changes, confusion, psychosis, and sleep disturbances over 3 weeks. Neurologist was consulted simultaneously and neurologic examinations were normal except confused mental status. Two months ago, she was diagnosed with Graves’ disease in another hospital and treated by methimazole 20mg per day. According to her parents’ statement, her thyrotoxic symptoms and thyroid function tests improved after initial medical treatment. However, her mental status dramatically altered 3 weeks before, associated with weight loss. Lab tests results showed no leukocytosis and thyrotoxicosis with marked high antithyroid antibodies: TSH 0.008 uIU/mL (normal 0.270-4.200), free T4 > 7.77 ng/dL (normal 0.93-1.70), T3 620.3 ng/dL (normal 84.6-201.8), TSH receptor Ab 83% (< 14%), thyroglobulin Ab 3443 IU/mL (< 115), anti-TPO Ab >13000 IU/mL (< 60). Head CT was performed and showed mild brain edema (Fig.1). HE was highly suspected and empirical steroid therapy given with intravenous Dexamethasone 4mg stat followed by daily Dexamethasone 3mg per day orally. The patient’s mental status dramatically improved and returned to the baseline after steroid treatment. After one month of antithyroid and steroid therapy with methimazole 30mg/day and Dexamethasone 3mg/day, her thyroid function much improved (TSH 0.009 uIU/mL, free T4 0.36ng/ dL, T3 620.3 ng/dL) and mental status stayed normal. Follow-up head CT revealed improved brain edema (more clear cortical sulci) (Fig.2).

The diagnosis of HE is based on neuropsychiatric symptoms, increased titers of antithyroid antibodies, and exclusion of other possible diseases. The most important presenting symptom of HE is altered mental status. Cognitive dysfunction, such as memory dysfunction and speech disturbance, is reported in 80% of patients, and behavioral changes are reported in 90%-100% of patients1,2. In most cases of HE, routine blood laboratory tests are normal. Hypothyroidism was observed in 52% of the reported pediatric patients, and 48% were euthyroid3. Comparison with our case, hyperthyroidism with HE is not frequent though with marked high anti-TPO Ab. Almost all reported cases of HE were

responsive to high doses of steroids4,5. It is usually administered by prednisolone at a dose of 1 g/d over 3 to 5 days. Clinical recovery usually occurs in the first 4 to 6 weeks of treatment, with varying treatment durations from 4 months to 10 years6. Plasmapheresis may be considered if the patient does not respond to the conventional treatment, such as steroids. Comparison with our case, she is good responsive to steroid and clinical recovery happened very soon. In the literature, most HE patients have a good prognosis, although there are no data on the long-term outcome of the disorder7.

PE-20 THYROID CANCER PRESENTED WITH AN INTERRUPTED PERIPHERAL CALCIFICATION IN SONOGRAPHY —A CASE REPORT

1WEI-HSIN HSU,

1I-MIN PAN, 2SHIH-MING HUANG, 3SHU-LING PENG, 4HAWCHIAO YANG, 5CHIANG-CHIN TSAI

1Department of Internal Medicine, 4Department of Radiology, 5Department of Surgery, Tainan Sin-Lau Hospital, Tainan, Taiwan; 2Department of Surgery, National Cheng Kung University Hospital, Tainan, Taiwan, 3Department of Pathology, National Cheng Kung University Hospital, Tainan, Taiwan

Peripheral calcification sometimes has been considered as an indicator of a benign nodule. We report a case of thyroid papillary carcinoma presenting with disrupted peripheral calcification in gray-scale sonography. A 39-year-old female complained of dizziness with whirling sensation for 4 months. On physical examination, blood pressure 104/71 mmHg, heart rate 87/min, mild thyroid enlargement. Thyroid function was within normal limits. Thyroid sonogram demonstrated an illdefined hypoechoic nodule with interrupted peripheral calcifications in left lobe, about 2.4cm in size and one tiny right thyroid cyst about 3mm. Fine needle aspiration did not disclose malignant findings. Total thyroidectomy proved to be a thyroid papillary carcinoma in left lobe.

PE-21 A CASE REPORT OF CUSHING DISEASE RELATED MULTI-SYSTEM FAILURE.

1SHEAU-FANG PAN, 2HARN SHEN CHEN

1Depeartment of Internal Medicine, Taipei City Hospital: Yang-Ming Branch, Taipei, Taiwan, R.O.C.; 2Section of Endocrinology and Metabolism, Department of Internal Medicine, Taipei Veterans General Hospital, Taipei, Taiwan, R.O.C

Cushing’s disease is caused by pituitary corticotropin (ACTH)-secreting tumors which lead to hypercortisolism. Patients present with high serum ACTH, serum cortisol, and urinary cortisol and 17-hydroxycorticosteroid. This patients with Cushing’s disease became immunocompromised and soon developed pneumonia and ARDS, cardiac myopathy with heart failure, GI bleeding, and renal failure. Patient received ECMO, machine ventilation, CCVH, and later hemodialysis as well as antibiotics, antifugal, inotropic support, and multiple blood transfusion. Patient improved and received endoscopic transsphenoidal surgery successfully.

PE-22 THE EFFECT OF THYROXINE SUPPRESSION THERAPY ON GOITER SIZE AND BONE MINERAL DENSITY IN POSTMENOPAUSAL WOMEN

CHIUNGYA CHEN, FENG-HSUAN LIU

Division of Endocrinology and Metabolism, Department of Internal Medicine, Chang Gung Memorial Hospital

Background: The prevalence of thyroid nodules was high in general population, especially in elderly and women. Suppressive thyroxine treatment in reducing the growth of nodules had been used for a long time but its efficacy and possible bone loss in postmenopausal women were still on debate. The aim of this study is to evaluate the effect of suppressive thyroxine treatment in the clinical management of thyroid nodules and the change of bone mineral density (BMD) in postmenopausal women during treatment. Methods: Ninety-four postmenopausal women diagnosed with nodular goiter or multinodular goiter at the Chang Gung Memorial Hospital (CGMH) between February 2001 and December 2017 were analyzed retrospectively. Forty-five patients receiving suppressive thyroxine treatment were defined as LT-4 group and 49 patients without thyroxine treatment were defined as control group. In LT-4 group, BMD of each subjects in LT-4 group were further measured. Results: The volume of nodules reduced during 2 years follow-up in both LT-4 group and control group, but there’s no significant difference in nodule size between these two groups. In the LT-4 group, the volume of nodule was decreased significantly in the initial 2 years (from 4.89 ± 4.46 to 4.10 ± 4.57 mL, P = 0.033), but there is no difference in the control group (from 3.48 ± 4.36 to 3.09 ± 2.88 mL, P = 0.239). However, when compared to baseline, the volume increased insignificantly later during 7 years follow-up (4.91 ± 5.40 mL, P = 0.711) and 9 years follow-up (6.06 ± 7.03 mL, P = 0.208) in LT4 group. The best cut-off value of nodule volume to be treated is 2.6mL (AUC=0.740, sensitivity: 0.750, specificity:0.733, P = 0.010) and the diminished thyroid volume in 21 patients (84%) was observed in LT-4 group during 2 years follow-up. During the thyroxine suppressive treatment, BMD had no significant change in lumbar spine (from 0.989 ± 0.134 to 0.981 ± 0.135 g/cm2, P=0.460), hip (from 0.806 ± 0.091 to 0.810 ± 0.094 g/cm2, P = 0.474) and femoral neck (from 0.742 ± 0.090 to 0.750 ± 0.083 g/cm2, P = 0.204) in 2 years. Conclusions: The volume of thyroid nodules reduced significantly in initial 2-years of suppressive thyroxine treatment in postmenopausal women and larger nodule (> 2.6 mL) had higher rate for volume reduction. Thyroxine suppressive treatment resulted in minimal effect in bone mineral density. But longer than 2 years of suppressive thyroxine treatment may not be benefit in nodule size control.

PE-23 STEMNESS ACTIVATION IN ADRENAL CORTICOMEDULLARY MIXED TUMOR STUDIED BY WHOLE EXOME SEQUENCING

1HSIN-YING CHIOU, 1HE-JIUN JIANG, 2SHEAU-FANG YANG, 1WEI-WEN HUNG, 1PIJUNG HSIAO

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

Background: Mixed corticomedullary tumor (MCT) is a single adrenal tumor containing both cortical and medullary cells intermixed throughout the entire neoplasm. It is extremely rare to be regarded as a new disease entity. Genetic mutation for the tumor formation is still unclear. We ever reported a 32-year-old female patient who has been diagnosed with a huge adrenal MCT. She was clinically manifested with typical Cushing’s syndrome. And mixed cortical adenoma and pheochromocytoma was documented both by biochemical and immunohistochemical evidences. This study aims to elucidate the etiology of MCT through decipher of the genetic mutations. Methods: Genomic DNA was extracted for whole exome sequencing (WES) using the high throughput next generation sequencing performed with Illumina HiSeq system. Before analysis, the tumor tissue was isolated as pheochomocytoma part (PHEO) and adrenal cortical adenoma (ACA) parts by pathologist. And patient’s blood was referred as a non-tumor control. Identified mutations were further validated by Sanger sequencing, and the related aberrant pathways were examined by immunohistochemistry. Results: There were 5,562 and 2,126 variants identified in ACA and PHEO parts respectively. Among these mutations, neither the known gene mutations of ACA (including GNAS,CTNNB1, PRKAR1A, PRKACA, PDE11A, PDE8B), nor that of PHEO (including RET, VHL, NF1, SDHA, SDHB, SDHC, SDHD, SDHAF2, TMEM127, MAX, EGLN1(PHD2), EPAS1(HIF2A), KIF1B, MET, and FH) were identified from this tumor. However, there were 1,559 variants co-existent in both ACA and PHEO parts. For all of the variants, 1,338 variants (85.8%) also occurred in blood sample. For further functional/pathway analysis, these mutated genes were associated with dominant enrichment of cell stemness regulation. The stemness expression, examined by immunohistochemical markers SOX2 and CD44, was significantly present both in ACA and PHEO parts. At the same time, this mixed tumor was also demonstrated with the aberrant MAPK signaling in PHEO part and extracellular matrix (ECM)-receptor interaction/Focal adhesion in ACA part by the pathway analysis from these PHEO/ ACA-specific mutation genes. Discussion and conclusion: From our result, adrenal MCT is actually a diverse disease entity different to pheochromocytoma or adrenal Cushing adenoma. This is the pilot study to provide molecular evidences to explore the etiology of adrenal MCT. From the significant expression of stemness markers in this case, it is speculated that germline mutations in stemness regulation may trigger the first hit for tumor formation. And the aberrant MAPK signaling and ECMreceptor interaction may stimulate further tumor proliferation and adhesion to intermix together.

PE-24 CLINICAL SIGNIFICANCE OF HEPATIC I-131 UPTAKE IN THYROID CANCER

1YI YIN LEE, 1SZU TAH CHEN

1Division of Endocrinology and Metabolism, Department of Internal Medicine, Chang Gung Memorial Hospital, Chang Gung University, Taiwan, R.O.C.

Objective: The purpose of this retrospective study was to determine the clinical importance of hepatic uptake of radioactive iodine after I131 ablative therapy in patients with thyroid cancer and if there is correlation between hepatic uptake and distant metastasis. Method: A total of five hundreds seventy six I-131 whole body scans performed (223 diagnostic scans and 353 post-therapy scans) on 40 patients with thyroid cancer (35 papillary, 3 follicular, 2 poorly differentiated) found to have once or more incidence of hepatic uptake were reviewed retrospectively from May1997 to Jan 2017 at Chang Gung Memorial Hospital (Taiwan). All patients received I-131 ablation therapy after bilateral total thyroidectomy. Thyroxine were discontinued around four weeks earlier or received thyrogen injection and had elevation of thyroid stimulating hormone level (TSH > 30 IU/ml) before radioactive iodine scan. Local uptake and diagnostic scan (2-10mCi) was performed at 24 hours and within 72 hours, respectively (early scan). The therapeutic scan (30-200 mCi) was performed and measured within 6-12 days (Late scan). Data including age, gender, histopathology and TNM stage were collected and divided into groups with or without distant metastasis. Serum thyroglobulin (Tg), TSH, serum Tg-Ab, serum ALT level and serum AST level were also obtained. Diffuse or focal hepatic uptake was visualized by well-experienced nuclear medicine physician that grading from 0: no uptake; 1: equivocal uptake; 2: faint or mild uptake; 3. Moderate or focal uptake; 4. Intense or diffuse uptake. For serum TSH, serum Tg, ALT and AST levels, the Mann-Whitney U test was used to measure the statistical significance between distant metastasis group and no distant metastasis group. The Pearson Chi-square test was used to analyze categorical variables. Results: The median age was 43.38 [33.60; 55.75] years and most of patients are females (N = 31; 77.5%). Among seven patients with distant metastasis, two patients showed diffuse hepatic uptake on the early scan. Four patients showed focal hepatic uptake and three patients revealed diffuse hepatic uptake. The serum levels of ALT, AST and serum Tg-Ab showed no significant difference between the two groups. Serum Tg showed higher level in distant metastasis group than no distant metastasis group (18.30 vs 0; p = 0.016). Conclusion: In our study, seven of forty hepatic uptake in I-131 whole body scan were found to have distant metastases. There was no significant difference of ALT, AST and serum Tg-Ab level between groups with or without distant metastasis group. Serum Tg seemed to be the only marker to predict distant metastasis in patients with hepatic uptake.

PE-25 FALSELY HIGH RESULTS IN MULTIPLE HORMONE IMMUNOASSAYS – A CASE REPORT

1HUI-CHUAN HSU, 2YA-CHIEH FANG, 3CHING-LING LIN, 4YI-HSUAN LI, 5LI-WEI YEH

1Divison of Endocrinology and Metabolism, Sijhih Cathay General Hospital, Taiwan, R.O.C.; 2Department of Endocrinology, and Radioimmunoassay Laboratory, Cathay General Hospital, Taiwan, R.O.C.; 3Division of Endocrinology and Metabolism, Cathay General Hospital, Taiwan, R.O.C.; 4Department of Laboratory Medicine, Sijhih Cathay General Hospital, Taiwan, R.O.C.; 5Chiu Hospital, Taiwan, R.O.C.

Abstract Objective: Immunoassay methods have been widely used in many important areas of health care for decades. These methods rely on the assay antibody detecting target analyte that could be an inherent drawback. With the advance of immunoassay technique, clinically significant interferences are uncommon. Here we share a case with endogenous antibody interfering with multiple hormone immunoassays. Methods: We present a case clinical history, laboratory data and methods to investigate immunoassay interference.

Results: A 61-year-old woman was referred to our outpatient department for an elevated thyroid-stimulating hormone (TSH) level of > 100 uIU/mL in her health checkup reports. After six months of levothyroxine replacement, TSH level remained high despite her free thyroxine level had reached above normal range. Pituitary image was a negative finding. Multiple hormone levels were unexpectedly high, including prolactin, luteinizing hormone, follicle-stimulating hormone and estradiol. Reanalysis with different platforms yielded discrepant results and was suggestive of immunoassay interference. Further investigation showed that the patient had a high level of rheumatoid factor. Patient sample treatment with heterophilic blocking tube could reduce falsely positive results in the same brand platform as well as the level of rheumatoid factor.

Conclusions: Base on a serial investigation, we believe this case with erroneously high results in many hormone tests caused by endogenous antibody interference. Clinicians need to be aware of them and alter to the mismatch of clinical feature and laboratory data. Early recognition would prevent inappropriate treatment.

PE-26 CLINICOPATHOLOGICAL FEATURES OF PAPILLARY THYROID CARCINOMA PATIENTS WITH POSITIVE BRAF V600E MUTATION: SINGLE CENTER EXPERIENCE IN TAIWAN

1HE-JIUN JIANG, 1CHIA-WEI LAI, 1WEI-LUN WEN,

1NAI-WEI SHEU, 1SHU-HENG HUANG, 1PI-JUNG HSIAO 1Division of Endocrinology and Metabolism, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan

Background: BRAF V600E point mutation is the most common genetic event in papillary thyroid carcinoma (PTC) worldwide. Theoretically, it may alter the MAP kinase/ERK signaling pathway to promote cancer cell growth and progression. However, the association between BRAF mutation and clinicopathologic significance of aggressiveness and recurrence remained controversial and was not fully documented in Taiwan population.

Methods: This was a retrospective cohort study to enroll total of 300 PTC patients, mean aged 45.4 (± 12.5) years, from January 1985 to December 2017. All of them were treated by total thyroidectomy and empiric radioiodine therapy and were kept continuous follow-up at our hospital for 40.1 (± 38.2) months. Genomic DNA was extracted from formalin-fixed paraffin-embedded tumor or lymph nodes specimens in tissue bank for BRAF mutation identification. The chi-square test was used to compare the significant difference of the clinicopathologic features between groups of V600E mutation and the wild type of BRAF gene.

Results: The frequency of BRAF V600E mutation was 51.7% (155/300) of PTC patients. Patient with BRAF V600E mutation significantly had bigger main tumor size (2.07 ± 1.21 cm vs 1.64± 1.33, p = 0.004 ), significant higher risk of extrathyroid extension (67.1% vs 46.2%, p < 0.001 ), especially gross extrathyroid invasion (9.0% vs 2.8%, p = 0.022), greater risk of harboring lymphovascular invasion ( 39.4% vs 24.1%, p = 0.005) and capsule invasion (29.7% vs 14.5%, p = 0.002 ) versus patients with wild type. Initially, there was no difference of lymph node metastasis (80.0% vs 76.6%, p = 0.469) and distant metastasis (2.6% v.s. 4.1%, p = 0.674) in both groups.

However, the cohort revealed higher tumor recurrence over lymph nodes (27.1% v.s. 16.6%, p = 0.028) and higher I131 accumulated dosage (165.6 ± 90.6 vs 143.8 ± 94.3 mCi) in group of BRAF V600E mutation than wild type group. Within this period, two cases positive of BRAF V600E mutation died but not any mortality in cases of wild type.

Conclusion: BRAF V600E point mutation was identified in more than half of PTC patients in our study. Carriers with BRAF V600E mutation significantly harbored more aggressive pathologic behavior, including extrathyroid extension, lymphovascular and capsule invasion, which could highly implicate the risk of disease recurrence. So, we strongly recommend to screen BRAF V600E mutation for PTC patients to determine proper treatment strategy and work-up for follow.

PE-27 METASTATIC POORLY DIFFERENTIATED THYROID CARCINOMA ARISING IN STRUMA OVARII WITH COEXISTENCE OF GRAVES` DISEASE AND MICROPAPILLARY THYROID CARCINOMA

1YA-MEI HSIEH, 1I-TEE LEE, 1YU-HSUAN LI

1Division of Endocrinology and Metabolism, Taichung Veterans General Hospital, Taiwan, R.O.C

Background: Poorly differentiated thyroid cancer originated from struma ovarii was rare cancer. There was limited evidence and treatment option in this group Case presentation: A 23 year old woman presented with urinary frequency and low abdominal mass. She underwent left side ovarian cystectomy. The cystic mass showed evidence of struma ovarii with poor differentiated transformation. There was no evidence of residual tumor or metastasis after patient received LSO+LN+omentum and Tc 99m scan. There was no evidence of recurrent tumor in the following two years. However, patient was bothered by anterior chest pain. Chest x-ray and CT disclosed multiple lung nodules and mediastinum lymphadenopathy. Metastasis from malignant struma ovarii was suspected according to cytology from sternal bone and histology of lung nodule. Micro-papillary carcinoma was found accidentally after total thyroidectomy. whole body scan showed partially uptake after 150mCi of radioactive iodine. Patient was under target therapy. Conclusions: Due to relatively higher possibility of metastasis and worse prognosis, Treatment protocol and follow up program should be build up in this group.

PE-28 SERUM BRAIN-DERIVED NEUROTROPHIC FACTOR PREDICTING REDUCTION IN PULSE PRESSURE AFTER A ONE-HOUR REST IN NURSES WORKING NIGHT SHIFTS

1I-TE LEE, 1WAYNE HUEY-HERNG SHEU

1Division of Endocrinology and Metabolism, Department of Internal Medicine, Taichung Veterans General Hospital

Night shift work is associated with cardiovascular disease and central nervous system disorders in female nurses. Brain-derived neurotrophic factor (BDNF) exerts protective effects on neural and endothelial functions. This study examined the association between serum BDNF levels and pulse pressure after rest in female nurses working night shifts. In this study, blood samples were collected for BDNF measurement after a night shift when nurses had been working night shifts for three continuous weeks. Blood pressure was assessed before and after a one-hour morning rest within a week of resuming the night shift after one month without any night shift work. The pulse pressure of nurses (n = 48, age 29 ± 5 years) was significantly reduced (from 43 ± 7 to 41 ± 6 mmHg, P = 0.003) after rest, and serum BDNF were significantly and inversely correlated with pulse pressure changes (r = -0.435, P = 0.002). Higher serum BDNF was an independent factor for greater reduction in pulse pressure (95%CI = -0.609 ‒ -0.174, P = 0.001). Using a receiver operating characteristic curve analysis, serum BDNF > 20.6 ng/mL predicted a pulse pressure reduction after a one-hour rest (sensitivity 66.7%, specificity 77.8%). In conclusion, higher serum BDNF predicted greater recovery of pulse pressure after a one-hour rest in female nurses after night shift work.

PE-29 HEPATOTOXICITY OF PROPYLTHIOURACIL (PTU) IN A BOY WITH GRAVES DISEASE

1,2,3,4,5YANN-JINN LEE, 1,4,6WEI-HSIN TING, 1,4,6CHI-YU HUANG, 7WAI-TAO CHAN, 1YA-TING CHIANG

1Department of Pediatric Endocrinology,MacKay Children’s Hospital; 2Department of Medical Research,MacKay

Memorial Hospital Tamsui District; 3Department of Pediatrics,School of Medicine,College of Medicine,Taipei

Medical University; 4Department of Medicine,Mackay Medical College; 5Institute of Biomedical Sciences,

Mackay Medical College; 6MacKay Junior College of Medicine,Nursingand Management; 7Department of

Pediatric Gastroenterology,MacKay Children’s Hospital

Thionamides including propylthiouracil (PTU), methimazole, and carbimazole are used to treat hyperthyroidism. The side effects include skin rash, granulocytopenia, abnormal liver function, and systemic vasculitis. PTU hepatotoxicity appears more often in children than adults. Therefore Nelson Textbook of Pediatrics recommends that PTU should not be used in children since 2011. However the caveat has not been noticed by all doctors. Children with hyperthyroidism are still exposed to the danger. We reported a boy with Graves disease treated with PTU had abnormal liver functionin about 2 months.

Patient report

A 7 7/12-year-old boy had a goiter and excessive appetite, heat intolerance, palpitation, and irritability. He was brought to a local hospital. His free T4 was 7.77 (ref 0.89-1.79) ng/dl and ALT was 53 (ref 12-27 IU/l). PTU (50 mg) twice daily was prescribed. His thyrotoxicosis improved and PTU was decreased to once daily 10 days later. A follow-up Free T4 was 1.91 ng/dl and TSH 0.01 µIU/ml at the 55th day of PTU treatment. At the 62nd day, he complained of fatigability, weakness, and anorexia. His ALT was 713 IU/Land AST499 (21-39) IU/L.PTUwas discontinued. Workups on infectious hepatitis or autoimmune hepatitis were negative. A follow-up ALT was 340 IU/Land AST140IU/Lbut T4 was 24.9 (ref 4.5-12.5) µg/dland T3 651 (ref 100-190) ng/dl 7 days later. He became severely thyrotoxic. Therefore carbimazole 0.5 tablet daily was started and then increased to 1 tablet daily in a day because free T4 was 7.76 ng/dl. His free T4 was 2.76 ng/dl, TSH < 0.03 µIU/ml, ALT 64 IU/l, and AST 50 IU/l in another 11 days. He was active with good appetite. His thyroid was 5 x 2 x 1 cm each side. His anti-TPO Ab was 727.8, anti-Thyroglobulin Ab 223 and antiTSH receptor Ab 68.85%.

Conclusion

PTU was hepatotoxic in a boy. The boy's liver gradually recovered afterthe discontinuation of PTU. PTUmust be avoided in children.