OD Oral Presentation-Diabetes (1-6

OE-01

PROTEOMIC ANALYSIS OF ANAPLASTIC THYROID CANCER CELLDERIVED EXOSOME FOR TUMOR THERAPY VIA LOVASTATININDUCED DIFFERENTIATION AND VILDAGLIPTIN-INHIBITED DIPEPTIDYL PEPTIDASE-IV (DPP-IV) ACTIVITY

1CHIH-YUAN WANG, 2HAO-AI SHUI, 2TIEN-CHUN CHANG

1Department of Internal Medicine, National Taiwan University Hospital and College of Medicine, National Taiwan University,Taipei, Taiwan; 2Graduate Institute of Medical Sciences, National Defense Medical Center, Taipei, Taiwan

Anaplastic or undifferentiated carcinoma cells proliferate rapidly and are easy to metastasize. Our the effect of Lovastatin on the undifferentiated thyroid carcinoma with the concentration of the dose is double-edged. In addition to Lovastation, inhibitors of Dipeptidyl peptidase-4 (DPP4, or CD26) may is involved in the proliferation and metastasis of prostate cancer cells and that DPP4 can promote or inhibit cancer cells by regulating their receptors, such as growth factors, chemokines, neuropeptides, and vasoactive peptides. In the study of prostate cancer also found that, DPP4 through the regulation of intracellular mitogenic peptide (mitogenic peptides) activity, thereby affecting the development of cancer. Vildagliptin is an inhibitor of DPP4 and belongs to the class of pancreatic islet enhancers. It is a potent and selective inhibitor of DPP4 activity and has been shown to promote the growth of intestinal cancer cells. Whether the drugs affect the growth of undifferentiated thyroid cancer cells is still unclear. It is now known that cancer cells tend to increase the survival rate of cancer cells through the expression of heat shock proteins (HSPs) to protect against environmental stress and to treat cancer drugs, or to regulate the proliferation of cancer cells via the mTOR signaling pathway. As described in the previous studies, both Lovastatin and Vildagliptin have an effect on cancer cell development, but whether these two drugs through the HSP and mTOR for thyroid anaplastic carcinoma or thyroid follicular carcinoma of the tumor cells is still unclear. In addition, HSP is also one of the biomarkers of the exosome surface of cancer cells. In clinical applications, exosomal proteins are considered to have the potential to predict the diagnosis, treatment and biomarker of health and disease. , Exosomes have After several tests, the results showed that ARO cells expressed DPP4 protein, and adding 1uM Vildagliptin and 25uM Lovastatin treatment of ARO cells and SW579 cells, found that Vildagliptin expression.

OE-02

THE CLINICAL SIGNIFICANCE OF OXIDATIVE MARKERS IN WELLDIFFERENTIATED THYROID CANCER

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.

Purpose: Age is a determinant factor for cancer staging and prognosis in well-differentiated thyroid cancer (WDTC). Since reactive oxygen species are age and disease, especially cancerassociated, the expression of oxidative markers (OM) such as serum total antioxidant capacity (TAC); glutathione peroxidase (GPX); myeloperoxidase (MPO) and urinary 8-hydroxy-2-deoxyguanosine (8OHdG) were compared in healthy subjects and patients with benign or malignant thyroid tumors to

Methods: Data were collected from 100 normal control (NC, 50 male and 50 female, aged 21.5 to 68.9 y/o) and 20 thyroid disease patients (5 male and 15 female, aged 28 to 67 y/o) during Sep 2013 to Aug 2014 from Chang-Gung memorial hospital. Among the thyroid disease group, OM were tested post-operatively in 15 WDTC (14 papillary and 1 follicular), pre-operatively in 1 follicular adenoma and 4 nodular goiter without operation (the five patients are classified as follicular neoplasm, FN). Each of the OM was analyzed as impact factor on gender and age; the association of OM with thyroid function, thyroglobulin (Tg), and total radioiodine (I-131) dose was studied in WDTC. Kruskal-Wallis one-way ANOVA, Mann-Whitney U test and Pearson correlation were applied in this study with the p

Results: Among the OM, TAC and 8-OHdG were highly disease status-associated; TAC and 8-OHdG showed the lowest and the highest levels in FN, followed by WDTC and NC, respectively. aged above 45 (P < 0.05 in all subjects and P < 0.01 in WDTC). GPX was highly and moderately correlated with Tg and accumulated I-131 dose in WDTC (R = 0.822, P < 0.001; R = 0.577, P = 0.024, the OM was correlated with TSH in WDTC regardless of metastasis or not.

Conclusion: We found that the structurally metastatic WDTC expressed significantly higher GPX, a selenium-containing enzyme, which was also significantly associated with serum Tg and accumulated I131 dosage. With these findings, GPX may be clinically available as a prognostic or even a diagnostic marker for advanced WDTC.

OE-03

URINARY IODINE ANALYSIS IN A THYROID CARCINOMA PATIENT REQUIRING RADIOIODINE THERAPY WITH PREVIOUS IODINATED CONTRAST AGENT USE

1FAN-FEN WANG, 2CHUN-JEN CHANG, 3KAM-TSUN TANG, 3GING-SHING WON

1Department of Medicine, Yangming Branch, Taipei City Hospital, Taipei, Taiwan; 2Division of Endocrinology and Metabolism, Department of Internal Medicine, Wan Fang Hospital, Taipei Medical University, Taipei, Taiwan; 3Division of Endocrinology and Metabolism, Taipei Veterans General Hospital, Taipei, Taiwan

Radioactive iodine (RAI) therapy is a beneficial, standard-of-care treatment for advanced differentiated thyroid cancer. Radioactive iodine uptake is increased by elevating thyrotropin (TSH) levels and initiating a low iodine diet (LID) prior to therapy. A pre-therapy spot urinary iodine concentration (UIC) of < 100 ug/L would support an adequate LID preparation. However, the use of iodinated contrast agents (ICA) is thought to interfere with the RAI therapy because of the enormous amount of iodine in these agents. We report a case of a post-thyroidectomy thyroid cancer patient requiring RAI therapy for pulmonary metastatic lesions but received ICA about 2 months prior to the scheduled radiation therapy.

Case report: This 75 year-old male was a patient of follicular thyroid carcinoma and had received total thyroidectomy. Before the thyroidectomy, computed tomography (CT) including ICA use had been performed as part of the work-ups to study the etiology of the multiple nodular lesions shown by plain chest X-ray study. At that time, aspiration cytology of the thyroid nodule had been lesions revealed follicular carcinoma of thyroid origin. After the thyroidectomy, he was on a LID in preparation for the RAI therapy.

The spot urine collected at the 45th, 46th, and 47th day (D45, D46, D47) after the CT scan were 47.6 ug/L, 614.5 ug/L, and 233.6 ug/L, respectively. Since the reading of D46 exceeded the calibration range of the assay, serial dilution was performed and yielded the result of 31.9 ug/L. In the assay without dilution, markedly decreased absorbance at 1 min after the Sandell-Kolthoff (S-K) reaction of D46 was found, and the condition was also found in D47. Serial dilution of D47 yielded the result of 51.5 ug/L. The patient received the scheduled RAI therapy under recombinant human TSH stimulation and the post therapy scan showed RAI uptake at the pulmonary metastatic lesions. Follow-up CT study at 5 months post RAI therapy showed decrease of the size of the pulmonary metastatic lesions. Serum thyroglobulin was 349 ng/ml (concomitant TSH 0.11 uIU/ml ; thyroxine suppression) before the RAI therapy and 118 ng/ml (TSH 0.97 uIU/ml; thyroxine suppression) at 4 months post therapy.

Conclusion: The current case demonstrated CT scan with ICA performed 2 months prior to RAI therapy didn’t inhibit RAI uptake. The unknown substance in urine interfering with the S-K reaction could be digested in diluted samples. 114

OE-04

NEUROENDOCRINE TUMOR OF THE THYMUS ASSOCIATED WITH ECTOPIC ACTH SYNDROME: CLINICAL MANIFESTATIONS OF TWO CASE STUDIES

1SHIH-CHEN TUNG, 2JUI LAN, 2JUI-CHU WANG

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

Introduction

Thymic neuroendocrine tumors (NETs) are exceedingly rare tumors, accounting for approximately 0.4% of all carcinoid tumors and < 5% of all anterior mediastinal neoplasms. The prognosis of patients with NETs is poor because of the high incidence of local recurrences and distant metastases, even after a radical tumor resection. We report the clinical manifestations of thymic NETs in two patients with ectopic ACTH syndrome.

Case reports

Case 1

A 53-year-oldman was admitted due to edema of face and bilateral lower limbs. Laboratory examinations showed baseline plasma cortisol > 60 ug/dL at 08:00, 24-h urinary free cortisol (UFC) > 480 ug/day, plasma ACTH 383 pg/mL, and plasma K 1.8 meq/L. Chest CT revealed bilateral lung nodules and chest wall masses, left anterior pleural tumor, left anterior mediastinal tumor, right T11 paravertebral mass, and diffuse mixed osteolytic and osteoblastic bony lesions. A pathological examination of bilateral chest wall biopsy showed neuroendocrine neoplasm of carcinoid tumor. An immunohistochemical (IHC) stain of the tumor revealed that it as positive for ACTH, chromograninA, synaptophysin, TTF-1, NSE, and Ki-67 in 3%. This is a carcinoid neuroendocrine tumor with ectopic ACTH syndrome and multiple organ metastases. The survival time from appearance of symptoms to death was 3 years and 5 months. Case 2 in the past 3 months. Laboratory tests showed that baseline plasma cortisol 110.6 ug/dL at 08:00 and 109.7 ug/L at 16:00, 24-h UFC 24310 ug/day, plasma ACTH 1480 pg/ml, and K level 2.2 meq/L. Sellar MRI did not reveal pituitary tumor. Chest CT demonstrated multiple small lung nodules, left anterior mediastinal nodule, mediastinal lymph nodes, left supraclavicular lymph node, precarinal lymph node, and right hilar mass encased pulmonary vessels. A pathological examination of resection of left lower lung, periarotic tumor, and mediastinal lymph nodes showed well-differentiated neuroendocrine carcinoma of the thymus with metastasis to lymph nodes. The results of IHC stain showed positive for ACTH, chromogranin A, synaptophysin, CD56 (N-CAM), AE1/AE3, Ki-67 1%, SSTR-2a, and SSTR-

5. This is a case of thymic neuroendocrine carcinoma with ectopic ACTH syndrome and multiple metastases. The survival time from appearance of symptoms (2011/06) to death (2013/04) was 10 months.

Conclusion

1. Ectopic ACTH syndrome should be considered if an ACTH-dependent syndrome patient combines with hypokalemia. 2. Thymic NETs are rare and very aggressive tumors with poor prognosis due to high incidence of recurrence/metastasis after surgery. 3. Thymic NETs associated with Cushing’s syndrome (CS) have poorer outcomes than those without CS. 4. The treatment of choice of NETs is surgical resection of the tumors and the involved neighboring organs.

OE-05

CASE SERIES OF THYROTOXICOSIS WITH LIVER FAILURE

1AN-CHI LIN, 1HAO-CHANG HUNG, 1YE-FONG DU, 1CHING-HAN LIN, 1HORNG-YIH OU

1 Department of Internal Medicine, Division of Endocrinology and Metabolism, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan

Objective

Profound hepatic dysfunction in thyrotoxicosis is infrequently reported in the literature, and its complicated with liver failure who were admitted to NCKUH during 2011 to 2014.

Methods

The clinical characteristics, thyroid function tests, causes of liver failure, and clinical courses of

Results

The range of the age was from 36 to 62 years old. Thyrotoxicosis-associated liver failure was clinical scenarios, our patients received different treatment for thyrotoxicosis, and ended up with diverse outcomes. Three patients recovered completely with no sequalae. However, two patients died of complications of sepsis and multiple organ failure despite intensive medical care.

Conclusions

Fulminant hepatic failure is a rare but serious complication of thyrotoxicosis. Jaundice in patients with thyrotoxicosis could be due to thyrotoxicosis itself, drug treatment for thyrotoxicosis, autoimmune hepatitis, or unrelated conditions like sepsis or viral hepatitis. Whether thionamides could be used in thyrotoxic patients with hepatitis and severe jaundice is inconclusive. The two fatal cases in our series were older in age, had multiple comorbidities, and complicated with sepsis and bacteremia. We suggest these factors to be poor prognostic indicators in thyrotoxic patients complicated with liver failure.

OE-06

CHROMOGRANIN A AND SYNAPTOPHYSIN EXPRESSION IN AN ALDOSTERONE, CORTISOL CO-SECRETING ADRENAL INCIDENTALOMA

1YU-CHUN HSUEH, 1HAN-WEN LIU, 1,2TING-I LEE, 1CHUN-JEN CHANG, 1YU-MEI CHIEN, 1,3TING -WEI LEE, 1CHI FAN

1 Division of Endocrinology and Metabolism, Department of Internal Medicine, Wan Fang Hospital, Taipei Medical University, Taipei, Taiwan; 2 Department of General Medicine, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan ; 3 Graduate Institute of Clinical Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan

Introduction:

Each adrenal glands are divided into two distinct parts, the cortex which originates from the mesoderm and the medulla that originates from the neural crest, ectoderm-origin. According to the cortex or medulla origin of an adrenal tumor, it can be separated into an adrenal-cortical tumor or pheochromocytoma, and the clinical manifestation differs as well. Here we present a patient with an adrenal incidentaloma co-secreting cortisol and aldosterone, with a positive chromogranin A and synaptophysin stains.

Case report:

The patient was a 62-year-old woman with hypertension and chronic hepatitis C. She received abdominal CT scan for follow-up of her liver tumor. The liver tumor was later proved to be a benign abdominal CT. Chemical shift imaging of adrenal MRI showed signal drop in out-of-phase images. Hormonal screening showed non-suppressible cortisol level on repeated 1-mg dexamethasone suppression test with low serum ACTH level. 24-hour urine free cortisol level, aldosterone-to-renin ratio, and 24-hour urine fractionated catecholamine level were negative. Adrenal incidentaloma with subclinical Cushing’s syndrome was diagnosed.

In the following years, patient had weight gain, diabetes mellitus, and non-traumatic compression fracture of T11 vertebra. Adrenal tumor size remained the same, but the aldosteroneto-renin ratio became positive. Primary hyperaldosteronism was later confirmed by captopril test. Considering the comorbidities caused by cortisol excess, she underwent laparoscopic left adrenalectomy. The microscopic images showed a cortical adenoma without nesting or other features of pheochromocytoma. But the immunohistochemistry stain showed positive synaptophysin and chromogranin A, which is usually seen in pheochromocytoma or adrenocortical carcinoma.

Discussion:

On literature review, there were few cases of histopathology-proven adrenal cortical carcinomas and adenomas posing as pheochromocytomas clinically. The other cases were corticomedullary mixed tumors with variable clinical symptoms, and cell features of both cortical and medullary components. In our case, the patient had benign cortical cells microscopically but with a positive investigations.