Poster Presentation

PP-01 A YOUNG ADULT WOMAN WITH SEVERE OSTEOPOROSIS DUE TO CUSHING’S DISEASE

YAN-RONG LI, CHIH-YIU TSAI, CHENG-WEI LIN, SZU-TAH CHEN, JEN-DER LIN, JAWL-SHAN HWANG

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

Background: Glucocorticoid-induced osteoporosis (GIOP) can result in loss of bone mass and eventually cause fractures of the ribs, long bones and spinal vertebra. Most people of GIOP is because of side effects of iatrogenic glucocorticoid use but not endogeneous glucocorticoid. Severe osteoporosis due to endogenous hypercortisonism was relatively uncommon in the clinical setting, especially for a young adult woman. Therefore, we present a case of a 35-year-old premenopausal woman with severe osteoporosis due to Cushing’s disease who presented with multiple low trauma fractures.

Case presentation: A 35-year-old was admitted to our orthopedic department because of left pubic bone fracture after falling from a standing height on a rainy day. She was a well-nourished, normal development, non-pregnant and premenopausal woman who never delivered a child. She ever got multiple rib fractures after slipping on the road one year before admission. She had regular menstrual cycles and denied smoking, alcohol consumption, taking any medication and drug containing ingredients of steroid or Chinese herb. According to her family history, her grandmother had oral cancer and two aunts had breast cancer. Physical exam showed no obvious finding except for overweight based on criteria in Taiwan (body mass index: 26.5 Kg/m2). She was referred to our oncologist’s and endocriologist’s service to rule out pathological fractures. Laboratory results showed 24-hour urine free cortisol (24-h UFC) was 1298.7 ug/day (normal range: 20.9 ~ 292.3 ug/day) with serum adrenocorticotropic hormone (ACTH) 68.4 pg/mL and positive high dose dexamethasone suppression test. Pituitary magnetic resonance imaging (MRI) revealed pituitary microadenoma (7x5x5 mm) in the left-sided pituitary gland. Transsphenoidal surgery for tumor resection was performed and the pathological result showed pituitary tissue with positive immunohistochemical study for ACTH. Severe osteoporosis due to Cushing’s disease was diagnosed definitely.

Conclusion: A young adult woman with severe osteoporosis due to Cushing’s disease was a relatively uncommon in our clinical practice. We hope that our experience of this case will remind physicians to be aware of this unusual complication of Cushing’s disease.

PP-02 AN ADRENAL ONCOCYTOMA PRESENTING AS CUSHING’S SYNDROME: CASE REPORT AND LITERATURE REVIEW

1CHIN CHOU YANG, 2CHENG HO CHUNG, 3CHIUNG MING HSU, 4TAO YUAN WANG, 5PEI SHAN TSAI

1Division of Endocrinology and Metabolism, Mackay Memorial Hospital, Hsinchu, Taiwan; 2Division of Endocrinology and Metabolism, Mackay Memorial Hospital, Taiwan; 3Department of Urology, Mackay Memorial Hospital, Taiwan; 4Department of Pathology, Mackay Memorial Hospital, Taiwan; 5Department of Radiology, Mackay Memorial Hospital, Taiwan

Adrenal oncocytomas are rare and the majorities were benign and non-functional. Of those that produce hormones, Cushing’s syndrome accounts for about 5.8%. We reported a 55-year-old woman presented with Cushing’s syndrome. The final diagnosis was adrenocortical oncocytoma.

Case presentation: A 55-year-old woman presented with body edema for 1 week and visited our endocrinologist. She has history of hypertension and type 2 diabetes mellitus with medication control for 2 years (Amlodipine, Valsartan, HydR.O.C.hlorothiazide, Propranolol, Metformin, Glimepiride). She also has history of nonalcoholic steatohepatitis with regular follow-up in our gastroenterology department. Weight gain of 8 kg (81 to 89kg) during past one year was noted. Her height was 153 cm, BMI was 37.5. Blood pressure was 170/111 mm Hg. Heart rate was 102 beat per minutes. She denied chest discomfort, palpitation, headache, or diaphoresis. Physical examination revealed nonpitting edema, centripetal obesity, buffalo hump, and moderate rounding of the face with puffy eye. Overnight 1mg dexamethasone suppression test (DST) revealed positive findings (Table-1). Two-day 2 mg DST was ordered, but the patient lost to follow-up. 9 month later, a right adrenal mass (6.3x4.8cm in size) was incidentally detected in abdominal CT scan during hepatic evaluation (Figure 1). She was then referred back to our endocrine department. The aldosterone, plasma renin activity, potassium and sodium levels were normal (Table-2). Two-day 2 mg DST yielded positive results (Table-3). We also checked urine cortisol and catecholamine (Table-4). The patient was then referred to urology department. Laparoscopic adrenalectomy was performed. The right adrenal gland including the tumor was completely removed. Microscopically, the adrenal gland showed a well-encapsulated mass composed of nests and trabeculae of polygonal cells with abundant granular, eosinophilic cytoplasm. Pleomorphic nuclei were focally seen. Rare mitotic figures were found. On immunohistochemical studies, the tumor cells were Melan-A(+), vimentin(+), synaptophysin (weak+), inhibin-α(weak+), and chromogranin-A(-).Necrosis, capsular invasion, or venous invasion was absent. The final diagnosis was adrenocortical oncocytoma. After discharged, she accepted dexamethasone supplement. Her body weight decreased up to 10% (94 to 83.3 kg within 9 months) and remained stable. There was no edema noted. Her blood pressure was relatively stable (systolic pressure around 120mmHg) under antihypertensive therapy with Valsartan and Amlodipine.

Discussion: Oncocytomas are uncommon and occur most commonly in the kidney (3-10%). These tumors have also rarely been seen in the salivary glands, thyroid gland, pituitary gland, parathyroid gland, lacrimal gland, respiratory tract, and choroid plexus with varying incidence (1). Adrenal oncocytomas are rare and the majorities were benign and non-functional (3). Since the first description in 1986 till 2014, less than 150 cases of adrenal oncocytomas have been reported (4). Usually, these tumors were incidentally discovered and only about 17% were functional (5). Of those that produce hormones, Cushing’s syndrome accounts for about 5.8%, based on the report of 2014 (6). These cases are extremely rare. So far, there are only 5 case of adrenocortical oncocytoma presented with Cushing’s syndrome found in the MEDLINE/PubMed search (MeSH Term: Cushing’s syndrome and adrenal oncocytoma). In our case, a 55 years old woman presented with a right incidental adrenal mass during evaluation for hepatic lesion, which was then removed by laparotomy. Conventional immunophenotype of adrenal oncocytoma are usually positive for vimentin, synaptophysin, inhibin-α, and Melan-A (7). In this case, Melan-A(+), vimentin(+), synaptophysin (weak+), inhibin-α(weak+), and chromogranin-A(-) were found (Figure 2). Together with structural findings of nests and trabeculae of polygonal cells with abundant granular, eosinophilic cytoplasm, a definite diagnosis of adrenocortical oncocytoma was made.

Pheochromocytoma should also be taken into consideration in our case because of minimal elevation of urine-norepinephrine, although the patient denied chest discomfort, palpitation, headache, or diaphoresis. However, the CT scan did not revealed marked enhancement of the tumor, which is helpful in differentiating benign oncocytic tumor from pheochromocytoma (11). Histologically, unlike oncocytoma, pheochromocytoma is originating in chromaffin cells. The chromogranin-A was negative in this case. According to above-mentioned results, we excluded the diagnosis of pheochromocytoma.

Although adrenocortical oncocytoma has been considered benign and the majority of reported cases had good prognosis, malignant case has ever been reported (8). In this case, a right adrenal mass (6.3x4.8cm in size) with punctate calcification and heterogeneous enhancement was noted. Malignancy should be considered on image study. However, there was no evidence found of being metastatic to other organs and lymph nodes, necrosis or focal invasion to surrounding structures. The tumor margin was also smooth. According to these findings, the case should be considered as benign.

Conclusion: Although most of adrenal incidentalomas are clinically silent, careful biochemical evaluations should be performed to differentiate nonfunctional from functional adrenal masses. The possibility of malignancy should also be taken into consideration. Our patient developed Cushing’s syndrome with an adrenocortical oncocytoma, which was confirmed by pathologic findings. Adrenocortical oncocytoma, although extremely rare, should be considered in the differential diagnosis of adrenal incidentaloma.

PP-03 A CASE OF ISOLATED HYPOGONADOTROPIC HYPOGONADISM WITH PARTIAL EMPTY SELLA FOLLOWING NORMAL COURSE OF PREGNANCY AND DELIVERY

1SHUN-HUO WANG, 2KUNG-YU WANG, 1CHIH-YUAN WANG

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

A 46 year-old woman suffered from secondary amenorrhea after her first time delivery for 18 years. She was pregnant at the age of 28 years. The delivery course was smooth without postpartum hemorrhage or other complication. However, she had only little amount breast milk (<100mL/day) and without recognized menstruation since then on. Hyperprolactinemia was noted later. She was prescribed with Cabergoline for one year, but still did not have further menstruation. Due to no other discomfort, the medication was withdrawn by herself.

To our unexpected surprise, she got spontaneous pregnancy without any medication at 32 years old. There were also only little breast milk without recognized menstruation. When she was 37 years old, her left mastitis took place. Documented serum prolactin was 32.0 ng/mL. Brain MRI showed partial empty sella. Cabergoline 0.5 mg weekly was prescribed, and the serum prolactin level decreased to below 0.1 ng/mL one month later with few vaginal spotting. Interestingly, she was pregnant again !

The third time post-partum condition stayed the same, but she refused further Cabergoline treatment. In 2015/04, she visited endocrinologic clinic due to dizziness. Our endocrine profile reported FSH 8.48 mIU/mL, LH 2.91 mIU/mL, E2 21.3 pg/mL, P4 <0.20 ng/mL, IGF-1 117 ng/mL, hGH 0.131 ng/mL, ACTH 15.8 pg/mL(8AM), Cortisol 9.05 μg/dL(8AM). Brain MRI remains partial empty sella.

We present a case of isolated hypogonadotropic hypogonadism with partial empty sella following once normal course of delivery with twice more spontaneous pregnancy.

PP-04 LY2963016 INSULIN GLARGINE VS LANTUS® INSULIN GLARGINE IN TYPE 2 DIABETES MELLITUS: EAST ASIAN SUBGROUP OF ELEMENT-2

1CHING-CHU CHEN, 2JU-FEN YEH, 3DAI CHIDA, 4JACEK KILJANSKI, 5LIZA ILAG, 5ROBYN POLLOM, 5DACHUANG CAO, 6KYUNG WAN MIN

1Division of Endocrinology and Metabolism, Department of Medicine, China Medical University Hospital, Taichung, Taiwan; 2Eli Lilly, Taipei, Taiwan; 3Eli Lilly Japan K.K., Tokyo, Japan; 4Eli Lilly, Warsaw, Poland; 5Eli Lilly and Company, Indianapolis, USA; 6Eulji General Hospital, Seoul, South Korea

BACKGROUND: The ELEMENT-2 study showed similar efficacy and safety profiles for LY2963016 Insulin Glargine (LY IGlar) and Lantus® Insulin Glargine (IGlar) in 756 patients with type 2 diabetes mellitus (T2DM). These are the results for the East Asian patient subgroup.

METHODS: The study included 32 Korean and 21 Taiwanese patients who were insulin-naïve (starting dose: 10 U/day) or receiving IGlar (starting dose: prestudy dose) and followed patient-driven titration (+1 U daily) until fasting blood glucose (BG) was ≤100 mg/dL. Patients received LY IGlar (n=26) or IGlar (n=27) in combination with ≥2 oral antihyperglycemic medications for 24 weeks. Outcomes included change in HbA1c, BG measures, hypoglycemia events (BG ≤70 mg/dL), and safety.

RESULTS: The within-group least squares mean (LSM) decrease in HbA1c from baseline to the 24-week endpoint was 1.17% for LY IGlar and 1.13% for IGlar. At the 24-week endpoint, LSM changes in fasting BG were 36.8 mg/dL and 32.6 mg/dL for LY IGlar and IGlar, respectively, daily mean BG was 31.9 mg/dL and 40.0 mg/dL, and the proportion of patients with HbA1c <7% was 57.7% and 46.2%. The mean rate of overall total hypoglycemia events was 20.8 and 14.7 events/patient/year and of nocturnal hypoglycemia events was 4.6 and 4.4 events/patient/year, for LY IGlar and IGlar, respectively. The incidence of treatment-related adverse events and injection-site adverse events was low in both groups. All statistical comparisons were p>.05. There were no statistically significant treatment-by-race interactions for any assessed outcome, indicating that the East Asian subgroup, in general, was similar to the overall population. Given the small numbers of patients in the East Asian subgroup, the numerical results are not intended to be applied to the general East Asian population.

CONCLUSIONS: Results from this small subgroup analysis provide insight into treatment outcomes in East Asian patients with T2DM; however, the analysis was not powered to assess similarity of outcomes.

DISCLOSURES: This study was supported by Eli Lilly and Company, Indianapolis, IN, USA. This is an encore of an abstract that has been submitted to the Japan Diabetes Society – 59th Annual Meeting, which will take place on 19 – 21 May 2016, in Kyoto, Japan.

PP-05 THYROTOXIC NEUROPATHY: REPORT OF A CASE

1SHIH-CHE HUA, 2PO-YEN YEH

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

Background: Neuromuscular disorders like acute and chronic myopathy, periodic paralysis, ophthalmoplegia, and rarely myasthenia gravis are known associations of thyrotoxicosis. However, neuropathy in thyrotoxicosis is not frequently recognized. We report a young lady with subacute sensori-motor neuropathy as the main presenting manifestation of thyrotoxicosis. Both thyrotoxicosis and neuropathy improved on antithyroid therapy.

Case Report: A 28-year-old woman presented with progressively worsening bilateral hand tremor, both lower limbs weakness and pain for two months. Her mother had past history of Graves’ disease. Examination revealed tachycardia of heart rate up to 130 bpm, a diffuse goiter of 5cm diameter, mild lower limb weakness (4/5, distal > proximal) and markedly deceased deep tendon reflexes in lower limbs (2/5). Investigations including blood counts, glucose, electrolytes, liver and renal functions, creatinine phosphokinase levels, urine analysis were normal. Imaging examinations including head CT and spinal MRI were normal. Rheumatology lab tests including ANA, antiDNA, c & pANCA, RNP Ab, Sm Ab, La Ab, Ro Ab, and Cardiolipin IgM were all negative. Blood test was negative for arsenic and lead. Thyroid function tests revealed thyrotoxicosis {TSH= 0.009 uIU/mL (normal 0.270-4.200), Free T4 =3.36 ng/dL (normal 0.93-1.70), T3 =214.9 ng/dL (normal 84.6-201.8)}. There were all positive for TSH receptor antibody was 58% (normal<14%), anti-TPO antibody was 599 IU/mL (normal<60), and thyroglobulin antibody was 112 IU/mL (normal<60). Thyroid ultrasound showed autoimmune thyroid disease. Nerve conduction studies revealed mononeuropathy, multiplex, sensori-motor, axonal type with decreased amplitude both in motor (left median, ulnar, bilateral peroneal and tibial) and sensory (bilateral sural). Antithyroid therapy with Methimazole 5mg/day combined with propranolol was initiated for 4 weeks. However, her neurologic symptoms and signs aggravated and elevated thyroid hormones levels (TSH= 0.011 uIU/mL, Free T4 =4.08 ng/dL) was noted 4 weeks later in the clinic. Follow-up nerve conduction studies revealed further markedly decrease in sensory amplitudes. Methimazole was titrated to 15mg/day then. Her neurologic symptoms and signs improved gradually associated with improved thyroid function test (TSH 0.060 uIU/mL, Free T4 =0.97 ng/dL, T3 97.3 ng/dL) and deceased TSH receptor antibody (33%) 12 weeks in the clinic. Follow-up nerve conduction studies revealed returned to nearly normal.

Discussion & conclusion: The literature for study on thyrotoxic neuropathy is few and the pathogenesis remains unclear. It may be due to the direct effect of thyroid hormone, immune mediated, or due to the hypermetabolic state depleting nerve of essential substances. We presented this case with

subacute polyneuropathy of two months duration and the absence of any other identifiable cause of neuropathy except thyrotoxicosis. Both of her clinical symptoms/signs and neural electrophysiological test were improved simply by antithyroid therapy with thyroid function approaching normal. Our case report suggests the clinical course of thyrotoxic neuropathy is reversible by antithyroid therapy.

PP-06 PRIMARY SQUAMOUS CELL CARCINOMA OF THYROID: A CASE REPORT

1HUNG-YI HUANG, 2SHIH-PING CHENG

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

Primary Squamous cell carcinoma of the thyroid is rare and usually has an aggressive clinical course. Poor response of radiation therapy, radioiodine and chemotherapy alone has been found ineffective in previously published case reports. Here we presest a 78 years old female, who complained of an enlarged left anterior neck mass with tenderness for over 6 months, with tracheal compression and underwent surgery and pathology revealed thyroid squamous cell carcinoma, and was treated with sorafanib.

PP-07 GLIMEPIRIDE-INDUCED HEMOLYTIC ANEMIA IN A GLUCOSE-6PHOSPHATE DEHYDROGENASE(G6PD) DEFICIENT PATIENT: A CASE REPORT AND LITERATURE REVIEW

CHUN-TA HUANG

Division of Endocrinology and Metabolism, Department of Internal Medicine, Mackay Memorial Hospital, Taipei Branch, Taiwan, R.O.C.

Introduction: Many medications have been implicated to cause hemolytic anemia in G6PDdeficient subjects. Among them, literature reports that oral anti-diabetic drug(OAD) sulfonylurea has rare but finite chance for this complication. Although U.S. Food and Drug Administration had posted a formal precaution, this potential side effect has not been well recognized. Herein, we report a case of glimepiride-induced hemolytic anemia in a G6PD-deficient man and make a literature review in search of evidence supporting this side effect.

Case Description: A 42-year-old Taiwanese male presented to our clinic with polyuria, polydipsia and body weight loss. Random blood glucose was 333 mg/dl so metformin 500 mg three times daily plus vildagliptin 50 mg once daily was prescribed for newly diagnosed diabetes mellitus. He returned to clinic five days later for lab results, which showed HbA1c 12.8%, serum creatinine 0.9 mg/dL, alanine transferase 40 U/ml and hemoglobin 16 g/dL. Glimepiride 2 mg twice daily was added after he refused insulin injection. Progressive icteric skin and tea-color urine developed several days later. He was admitted for further studies, approximately 10 days after starting glimepiride.

Upon admission, his hemoglobin was only 7.9 g/dL with normal platelet count and elevated reticulocyte count. His stool was hemoccult negative and blood smear discovered polychromatophilic red blood cell. Biochemistry data disclosed indirect-type hyperbilirubinemia, low haptoglobin and elevated lactate dehydrogenase level, raising the suspicion of hemolysis. Metformin and glimepiride were replaced with insulin while vildagliptin was kept for no literature has reported its linkage to hemolysis. His hemoglobin dropped further to 6.5 mg/dL on the next day and blood was transfused. Final reports were negative for both indirect and direct Coombs tests while G6PD quantitative level was very low, compatible with G6PD deficiency. After cessation of the offending drugs, his hemoglobin rose steadily to 7.7 mg/dL and he was no longer icteric. The patient was discharged on the 7th day of his admission and metformin was resumed another week later. Hemoglobin in the following month was 12.5 mg/dL without other abnormal lab data.

Method: Medline database was used to search English articles published before 2015 using “hemolysis”, “hemolytic anemia” and “Glucose-6-Phosphate Dehydrogenase deficiency” as screening keywords. The eligible results were further cross-matched with “sulfonylurea” and generic names of all OAD in this category such as “tolbutamide”, “glibenclamide”, “glimepiride” etc., in

one by one fashion.

Result: Total 13 sulfonylurea-related hemolysis case reports were identified, mostly by an immune-related mechanism. Only 3 cases were confirmed to be G6PD-deficient without other identifiable causes of their hemolysis. Of the 3 subjects, one received tolbutamide and two had glyburides. All patients recovered after drug cessation and none of them had drug rechallenged.

Conclusion: Although limited data support the risk of sulfonylurea-related hemolysis in G6PDdeficient patient, one should still keep this rare but finite side effect in mind. Further studies are needed to validate this relationship.

PP-08 POORLY CONTROLLED HYPERTENSION IN A CASE WITH 17-Α HYDROXYLASE DEFICIENCY

1YIN-HUEI CHEN, 1ZI-YUAN WANG, 2YEN-NIEN LIN, 1CHING-CHU CHEN, 1CHINGCHUNG CHANG, 1YI-CHIN HUNG

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

17α-hydroxylase deficiency contributes rare entity of congenital adrenal hyperplasia and commonly presents hypertension and hypokalemia. However, the underlying mechanism of hypertension is different between 17α-hydroxylase deficiency and hyperaldosteronism. Incorrect blood pressure management may result in refractory hypertension and cardiovascular complication. Here we shared a young female presented with resistant hypertension and hypokalemia. She was complicated with left ventricular hypertrophy. After physiologic prednisolone supplement, her blood pressure was better controlled and hypokalemia was also corrected. Our case highlighted the importance of supplement in glucocorticoid pathway in care of patient with 17 alpha-hydroxylase deficiency.

PP-09 ACUTE APPENDICITIS: A RARE PRESENTATION OF ANTI-THYROID DRUG INDUCED AGRANULOCYTOSIS

YI-CHEN WU, RONG LIN

Division of Endocrinology and Metabolism, Department of Internal Medicine,Far Eastern Memorial Hospital, Taiwan, R.O.C.

Anti-thyroid drug induces agranulocytosis is rare(0.35%).1 The common symptoms are sudden onset of fever and sore throat. However, acute appendicitis may be a rare presentation.

Case report: We presented a 60-year-old female without systemic disease. She suffered from palpitation and body weight loss and final diagnosis was Graves’ disease. Carbimazole 30mg daily was initially prescribed for 35 days. After followed thyroid function became lower (3-rd TSH:<0.004 to 0.007 uIU/mL and free T4:2.67 to 1.84 ng/dL), carbimazole was reduced to 20mg daily. 23 days later, the patient suffered from fever with RLQ pain. Lab examination showed agranulocytosis(WBC 220/ uL, ANC 0/uL) which suspected carbimazole related. Emergency abdominal CT was arranged due to peritoneal sign was noted which disclosed acute appendicitis. Emergency laparoscopic appendectomy was done and acute suppurative appendicitis with focal abscess was found. We chose broad spectrum antibiotic Piperacillin/Tazobactam and then descalated to ceftazidime according to her blood culture revealed P.aeruginosa finally. G-CSF(granulocyte colony-stimulating factor) 300mcg was used for 8 days and her absolute neutrophil counts rised to more than 500/mm3 on the 9th day. After the patient was recovered from acute appendicitis and agranulocytosis, she was discharged. 10mCi I-131 ablation therapy was arranged for her in out-patient department. Hypothyroidism developed one month later and thyroxine 100mcg daily was prescribed for her.

Discussion: The incidence of anti-thyroid drug induces agranulocytosis is rare (methimazole 0.35%, propylthiouracil 0.37%).1 The most common associated symptoms are sudden onset of fever and sore throat. The average time to onset is 69 days (range11-233 days, our case 58 days).2 A case series(13 patients) in Taiwan in 9 patients developed agranulocytosis under the doses of methimazole or carbimazole of 15 to 30 mg/day (mean SD: 22.78 7.12mg/day).3 Empiric broad spectrum antibiotic (including coverage for possible pseudomonas infection) should be used initially.1 For the management of hyperthyroidism which includes thionamide, radioiodine ablation, or surgery.4 Radioiodine ablation or surgery wound be considered if sever side effect of thionamide happened. For our patient, acute appendicitis is a rare presentation of carbimazole inducing agranulocytosis and we should be aware of initially.

PP-10 CASE REPORT: CONGENITAL ADRENAL HYPERPLASIA, 21 ALPHAHYDROXYLASE DEFICIENCY, SALT-WASTING TYPE

1CHIN-FAN CHEN,

2CHI-YU HUANG, 2YANN-JINN LEE, 2WEI-HSIN TING, 3CHAO-HUNG WANG, 3MING-NAN CHIEN, 1YA-CHUN HSIAO

1Division of Endocrinology and Metabolism, Mackay Memorial Hospital,Hsinchu City, Taiwan, R.O.C.; 2Division of Pediatric Endocrinology and Metabolism, Mackay Memorial Hospital, Taipei, Taiwan, R.O.C.; 3Division of Endocrinology and Metabolism, Mackay Memorial Hospital, Taipei, Taiwan, R.O.C.

6-day-old male neonate was born to a G1P1 28-year-old healthy mother with BBW of 2940 grams at GA 40+1 weeks via vaginal delivery at GYN clinic. After birth, hypospadias and bilateral undescended testis were found. Besides, neonatal jaundice occurred, then the baby was referred to our hospital. After admission , PE showed BL 50cm, BW 2.94kg, ambiguous genitalia, hyperpigmentation of scrotum and nipples, hypospadias and bilateral cryptorchidism, pallus 2.5x 1.3 cm. Newborn screen reported 17 alpha-OH-progesterone 80ng/ml. Laboratory data included total/direct bilirubin 20.8/0.9 mg/dL, hyponatremia 131mEq/dL, hyperkalemia 5.8mEq/dL. Hormone profile found low FSH and LH, cortisol 2.34μg/dL, ACTH 538.60 pg/mL, high aldosterone 72.5 ng/dL, high plasma renin activity >50 ng/mL/hr were found. Hemolytic disease of newborn(HDNB) revealed negative direct and indirect antiglobulin test (DAT, IAT), low G6PD 9.7 U/gHb (reference range 12.5-21.6). Abdominal ultrasound found uterus and adrenal gland enlargement. VCUG was remarkable. Congenital adrenal hyperplasia, suspect 21-alpha hydroxylase deficiency, salt wasting or female virilization type was impressed. Cortisone acetate 25mg 0.2 tabs BID and FludR.O.C.ortisone 1 tab were prescribed since 2014/4/15. Pediatric plasty surgeon was consulted. Genetic study evidenced CYP21A2 gene mutation. We shared the experience and special characteristics of congenital adrenal hyperplasia. The routine newborn screen is very important in neonatal metabolism and growth. The molecular analysis of genetics provides the evidence of the subtype and gender difference.

PP-11 LARGE BILATERAL ADRENAL MASS IN A 43-YEAR-OLD MAN: A CASE REPORT

SHIHCHANG LO, EDY KORNELIUS, CHIEN NING HUANG

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

Introduction: We report a bilateral large adrenal tumor (7cm) in a 43-year-old man with the presentation of abdominal fullness, anorexia and epigastralgia.

Case: A 43-year-old man presented with a 3 weeks history of progressive abdominal fullness, anorexia and epigastralgia. He had significant weight loss from 65 kilogram to 60 kilogram in 3 weeks. He visited local hospital 2 days ago, and panendoscopy discovered an ulcerative mass at stomach. He was referred to Chun-Shan medical university hospital for further investigation.

Physical examination was unremarkable except epigastric tenderness. Mild hypotension (102/56 mmHg) without tachycardia was found at admission. The blood pressure was not changed after intravenous hydration and as his baseline level. Contrast abdominal CT showed large solid mass in bilateral adrenal gland with heterogenous enhancement (left side 5 x 7 cm; right side 7 x 7 cm). In addition, there were three separate gastric tumor, multiple confluent lymph nodes and several round pulmonary nodules, suggesting metastasis. Laboratory test results revealed normal blood count, serum electrolyte and serum creatine. 24-hour urinary Norepinephrine (32.5 ug/day), Epinephrine (16 ug/ day), Dopamine (400.3 ug/day) and VMA (4.1 mg/day) were within normal limit. Endocrine profile showed plasma Cortisol 14.2 ug/dl, ACTH 51.2 pg/ml, Aldosterone 43.1 pg/ml, PRA 2.22 ng/ml/hr.

Panendoscopy discovered two ulcerative mass lesion at gastric body and one round mass with intact mucosa at lesser curvature, all lesions were biopsied. The pathological report were metastatic melanoma (Melan-A +, CK -, S100 +, LCA -, HMB45 +). Subsequent investigation was suggested but the patient refused and sought the secondary opinion.

Conclusion: Adrenal gland is one of the common site of metastatic melanoma. Patients with melanoma adrenal metastasis have a poor prognosis. Surgical treatment should be considered only in highly selected patients.

PP-12 25 Years Old Man with Central Diabetes Insipidus

1,2BAO-MEI WANG, 1,2,3CHING-CHIEH SU

1Department of Internal Medicine, Cardinal Tien Hospital, Xindian, New Taipei City, Taiwan; 2Division of Endocrinology, Department of Internal Medicine, Cardinal Tien Hospital, Xindian, New Taipei City, Taiwan; 3School of Medicine, Fu-Jen Catholic University, New Taipei City, Taiwan

Introduction: Diabetes insipidus can be caused by lymphocytic infundibuloneurohypophysitis, which could be detected by MRI. The natural course of the disorder is self-limited.[1] In the case report, we presented a young man with highly suspected infundibuloneurohypophysitis radiologically.

Case presentation: This 25 years old man came to our endocrine outpatient department for frequent thirst and polyuria for 2 months. He noticed polydipsia(30L/day) and polyuria (10L/day) in these 2 months. He denied systemic illness, nor took any drugs such as lithium, demeclocycline. There was no glycosuria and HbA1C was 6.3%.His initial serum sodium was 141mmol/L, blood osmolarity 308 mosm/kg, urine osmolarity 108mosm/kg. Water deprivation test was arranged during admission. Serum and urine osmolarity, body weight were monitored every 1-2 hours. During water deprivation test, gradual rise of serum sodium and osmolarity was noted, as well as urine osmolarity. DDAVP nasal spray was given when urine osmolarity was stable for 3times. Rapidly increased urine osmolarity was noted. Therefore central diabetes incipidus was diagnosed and sella MRI was arranged which showed infundibuloneurohypophysitis with possible differential diagnosis of lymphocytic hypophysitis, histiocytosis,germ cell tumor, neurosarcoidosis. His serum cortisol (8AM) 21.59μg/dl, ACTH 36.1pg/ ml,testosterone 217.25ng/ml, FSH 5.49m IU/ml, LH 2.58 m IU/ml, free T4 1.54ng/ml, TSH 1.286μU/ ml HGH 0.036 ng/ml, IGF 1 124ng/ml. There was no sign or symptom of deficiency of anterior pituitary hormones. Therefore neurosurgeon was consulted for surgical intervention and transphenoidal surgery was performed. During surgery, anterior lobe specimen was sent to pathology which disclosed normal anterior lobe. However, CSF leakage was noted thereafter. Therefore, surgery was discontinued without any specimen of posterior lobe. Patient was discharged with regular minirin for DI.

Discussion: Central diabetes insipidus is a chronic disorder characterized by polyuria and polydipsia due to vasopressin deficiency. The disorder may be familial, idiopathic, or secondary. Familial diabetes insipidus is characterized by autosomal dominant inheritance and, at least in some families, mutations of the vasopressin-neurophysin II genes. Secondary diabetes insipidus, the most common form of the disorder, is caused by tumors, infections, trauma, or other processes (such as histiocytosis and vascular lesions) that damage the hypothalamic-neurohypophysial system. Idiopathic diabetes insipidus, which accounts for 10 to 30 percent of cases of central diabetes insipidus, is

characterized by selective hypofunction of the hypothalamic-neurohypophysial system. Antibodies against magnicellular neurons of the hypothalamus have been detected in some patients, leading to speculation that it is an autoimmune disorder[1] Deterioration of pituitary function was only found in patients with progressive lesions. The initial response to glucocorticoid pulse therapy was most favorable, with early failure in only 3%. However, the overall failure and recurrence rate was 41%. Recurrence rate was not related to duration of steroid administration. Side effects of steroids occurred in 63%. The surgical approach was transsphenoidal in 94%. The histological subtype was lymphocytic hypophysitis in 70% and granulomatous hypophysitis in 30%. Progression or recurrence was observed in 25% after surgical treatment.[2]

Conclusion: Infundibuloneurohypophysitis is inflammatory process, was self-limited and regressed spontaneously, perhaps after the destruction of all neurons. This sequence is compatible with the autoimmune hypothesis of idiopathic diabetes insipidus.

PP-13 DIABETIC KETOACIDOSIS AS THE INITIAL PRESENTATION OF ACROMEGALY

1YUNG-HSIN TSAI, 1,2SHYANG-RONG SHIH

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

Introduction: Excessive growth hormone (GH) impairs glucose metabolism by increasing insulin resistance, lipolysis and hepatic gluconeogenesis. About 19–56% of acromegaly patients developed diabetes mellitus (DM), but diabetes ketoacidosis (DKA) rarely occurred. Here we report a case of acromegaly who presented with DKA initially.

Case report: A 45-year-old man with no prior medical history presented to our emergency room with dyspnea and weakness for one week. He also complained of polyuria and polydipsia in this week and weight loss for one month. Laboratory examinations showed high plasma glucose and ketoacidosis (plasma glucose: 966 mg/dL, HbA1C: 13.2%, plasma ketone: 6.1 mmol/L, arterial pH: 7.142). DKA was diagnosed and treated. Because the response to insulin therapy was poor, secondary causes of hyperglycemia were judiciously surveyed. Serum GH and insulin-like growth factor (IGF-1) were measured while there was subtle acromegaloid appearance, including mildly enlarged nose, fingers and toes. The results were abnormal (GH: 29 ng/mL, IGF-1: 468 ng/ml). Magnetic resonance imaging disclosed a pituitary macroadenoma measured 1.7 cm in diameter. Insulin requirement decreased after metformin prescribed, and further decreased to zero 4 days after trans-sphenoidal adenomectomy. GH and IGF-1 were then normalized and no anti-hyperglycemic medication was required 3 months after operation.

Conclusion: We demonstrated a case of GH induced severe hyperglycemia with DKA, which was a rare initial presentation of acromegaly. Treatment of acromegaly would reach the resolution of DM. Judicious work-up for the secondary causes of hyperglycemia should be performed in all patients with difficultly controlled DM.

PP-14 SEVERE SYMPTOMATIC HYPERCALCEMIA - CHRONIC TOPHACEOUS GOUT AS THE POSSIBLE TRIGGER?

1CHEN-TI WANG, 1, 2YUNG-CHUAN LU, 1YU-HSI KAO, 1SHU-JU KU, 1KUO-BIN TSENG

1Division of Endocrinology and Metabolism, Department of Internal Medicine, E-DA Hospital, Kaohsiung, Taiwan; 2School of Medicine for International Students, I-Shou University College of Medicine, Kaohsiung, Taiwan

Hypercalcemia is common in clinical practice and most of the cases are due to hyperparathyroidism and malignancy. Hypercalcemia has also been associated with granulomatous diseases, which is due to enhanced extra-renal conversion of calcidiol to calcitriol by activated macrophages within the granuloma.

We report a case of symptomatic hypercalcemia possibly due to chronic tophaceous gout induced granulomatous inflammation. The patient was a 52-year-old man with past history of a 30year history of gouty arthropathy with extremities deformity without any treatment. He was presented to the emergency department with altered mental status characterized by confusion, slow verbal response and lethargy. Multiple tophi had appeared on bilateral knees, elbows, hands and feet for years and he was sometimes confined to bed most of the day due to intense generalized pain. Physical examination revealed altered mental status characterized by lethargy and a Glasgow Coma Scale of 14 without focal neurological deficits. Multiple gouty tophi were obvious at inspection over bilateral wrists, elbows, metacarpophalangeal, proximal and distal interphalangeal joints, knees, ankles and the metatarsophalangeal joints. The rest of the examination was unremarkable. Laboratory tests revealed elevated uric acid (UA: 10 mg/dl; normal range 4-8.5 mg/dl), elevated calcium (Ca: 14.7 mg/dl; normal range 8.8-10.3 mg/dl), elevated phosphorous (P: 5.3 mg/dl; normal range 2.7-4.5 mg/ dl), elevated creatinine (Cr: 3.2 mg/dl; normal range 1.1-1.5 mg/dl), low intact-PTH (iPTH: 9 pg/ml; normal range 15-68.3 pg/dl), low 25-hydroxy vitamin D (25(OH) Vitamin D: 17 ng/ml; normal range 32-100 ng/ml), low hemoglobulin (Hb: 6.5 g/dl; normal range 13.5-17.5 g/dl), elevated squamous cell carcinoma (SCC: 3.5 ng/ml; normal range 0-1.5 ng/ml), normal levels of alphafetaprotein, carcinoembryonic antigen, prostatic specific antigen. It was not possible to check PTH-related peptide and 1,25-dihydroxyvitamin D in our laboratory setting. Upper gastrointestinal panendoscopy revealed gastritis and gastric ulcers. Bone marrow biopsy result showed normocellular bone marrow with small aggregates of plasma cells. Bone scan showed no evidence of bone metastasis and was consistent with gouty arthritis with multiple tophi. Gallium scan revealed moderate inflammatory pR.O.C.ess in over multiple joints, consistent with chronic gouty arthritis with multiple tophi and gout granuloma. Excisional biopsy of tophi over right thigh was arranged and pathology showed amorphous material

surrounded by histiocytes and multinucleated giant cells, and result is consistent with gouty tophi. Chest computed tomography revealed a small nodule about 4 mm in size in right upper lobe. The lung nodule was too small to perform biopsy. Treatment during hospitalization included intravenous saline solution, bisphosphonates and prednisolone with a subsequent restoration of normocalcemia and improvement in renal function. Patient’s presenting symptoms were also resolved and he was discharged in stable condition.

Hypercalcemia is relatively common in clinical practice and the majority of the cases are accounted for hyperparathyroidism and malignancy. Hypercalcemia has also been described in patients with various types of granulomatous disorders, with sarcoidosis being most widely evaluated. However, the association of chronic tophaceous gout with severe hypercalcemia is infrequent. The postulated mechanism is an enhanced 1α-hydroxylation of calcidiol to calcitriol by the activated mononuclear cells within the granuloma. Monosodium urate crystals in patients with chronic tophaceous gout are thought to act as the inciting antigen that leads to an intense inflammatory reaction of giant cells, macrophages and lymphocytes. It was impossible to check PTH-related peptide and 1,25-dihydroxyvitamin D in this case. In addition, the nature of the lung nodule is unknown. Hyercalcemia induced by malignancy might see an increase of PTH-related peptide. Granulomatous induced hypercalcemia may cause an increase of 1,25-dihydroxyvitamin D. Without these laboratory data, it was difficult to distinguish the actual cause of hypercalcemia in this case. Immobilization is another known cause of calcium elevations and it is likely that this was an exacerbating factor in this case. Since the patient in this case presents with multiple tophaceous gout, association with hypercalcemia should also be taken into account. It would be an interest to check calcium levels in patients with chronic tophaceous gout to determine whether hypercalcemia is a common association.

PP-15 PITUITARY STALK LESION WITH PARTIAL CENTRAL DIABETES INSIPIDUS-A CASE REPORT

1YIN-HUEI CHEN, 1RONG-HSING CHEN, 2YEN-NIEN LIN, 1CHING-CHUNG CHANG

1Division of Endocrinology and Metabolism, Department of Internal Medicine, China Medical Univetsity Hospital; 2Division of Cardiology , Department of Internal Medicine, China Medical Univetsity Hospital

Central diabetes insipidus (CDI), characterized by a deficiency of arginine vasopressin, is uncommon. Causes of CDI include traumatic, infiltrative, inflammatory and neoplastic disorders of the pituitary or hypothalamus. Here in, we reported a 31 year old woman who presented with CDI due to thickened pituitary lesion. After differential diagnosis, we suspected she suffered from lymphocytic hypophysitis. With daily 20ug desmopressin nasal spray, her polyuria improved. At last, we also made literature review about pituitary stalk lesions.

PP-16 ACUTE ENLARGING GOITER AFTER INTRAVENOUS THROMBOLYSIS FOR SEVERE DEEP VEIN THROMBOSIS

1YIN-HUEI CHEN, 1CHING-CHU CHEN, 1CHING-CHUNG CHANG, 1CHWEN-TZUEI CHANG, 2YEN-NIEN LIN, 2CHIUNG-RAY LU

1Division of Endocrinology and Metabolism, Department of Internal Medicine, China Medical University Hospital; 2Division of Cardiology , Department of Internal Medicine, China Medical University Hospital

Nowadays, treating extensive proximal DVT had been changing with the advent of catheterdirected thrombolysis using tPA or Urokinease directly and slowly into venous thrombus via multisidehole catheter. Clinically relevant bleeding complication was less than 10%. Spontaneous hemorrhage in thyroid cysts and adenoma is common and asymptomatic. Here in, we presented a case sufferred from acute enlarging goiter after intravenous thrombolysis for severe deep vein thrombosis. Our case highlighted that closed surveillance of neck during thrombolytic therapy in patients with goiter is important.

PP-17 A NEWLY ONSET DIABETES PRESENTING WITH DKA DUE TO GAS-FORMING PYOGENIC LIVER ABSCESS COMPLICATED WITH PNEUMOPERITONEUM

JUIHSIANG LI, CHI CHAO WANG

Tao-Yuan General Hospital

Introduction: Pyogenic liver abscess is an infective disease of the liver, accounting for 8 to 25 cases per 100, 000 hospital admissions. Gas-forming pyogenic liver abscess (GFPLA), which accounts for 7 to 24% of pyogenic liver abscess, has a high fatality rate in spite of aggressive management (27.7 to 37.1%) (. They usually appear as an acute disease with malaise, nausea, anorexia, fever, jaudice and right upper-quadrant pain. Blood cultures are positive in 52% of the cases and the pathogens are Streptococcus species and Escherichia coli while in Taiwan the most common pathogen is Klebsiella pneumonia . Diabetic patient is immunocompromised. The disease presentation is sometimes atypical . We presented an unusual case of newly diagnosed diabetes admission with DKA due to Gas-Forming Pyogenic Liver Abscess complicated with pneumoperitoneum

Case report: A 54 year-old woman had only hypertension in previous medical history. She had poor appetite and nausea recently. She ever received panendoscopy and the result showed only gastritis. Her symptoms got worsen with nausea, vomiting and general malaise for one week. She was brought to our ER for help. Findings at initial assessment at our emergent room were as follows: body temperature, 37.2∘C; blood pressure, 149/56 mmHg; regular pulse, 99 beats/min, respiratory rate , 19 times/min; weight, 53kg ; body mass index, 21 . Physical examinations indicated that the patient was clear in consciousness, had weakened appearance, anicteric sclera and smooth respiratory pattern . However, the physician did notice mild abdomen distention, but no tenderness, no rebound pain. The remarkable blood biochemistry studies showed as follows: leukocytosis with left shift (WBC=21790, seg/band/lym=69.5/17.2/3.8, Hb=13), CRP=18.63, hyperglycemia (sugar=414), A1c=16.4%, hyponatremia(Na=132), normal liver function test (AST/ALT=33/33), Vein blood gas with metabolic acidosis, (PH/pCO2/PO2/HCO3-/Be=7.098/17.3/50.6/5.2/-22.4), blood ketone body=3.7 mmol/l (reference<0.6), lactic acid=0.9 mmol/l, glycosuria and ketouria with no pyuria (glucose 4+, ketone4+, WBC=0-2/HPF), normal chest X ray image and ileus in KUB image.

IV insulin and empiric anbitiotics ( cefoxin) was given. Fever (39.6°C) was noted after admission. She complained of severe abdominal pain 2 days later. We arranged chest X-ray and KUB image. Right subphrenic air was noted. Hollow organ perforation was suspected. Emergent abdominal CT was performed and an irregular lobulated lesion with air collection and rim enhancement in lateral segment of liver R/O abscess formation. The impression is pneumoperitoneum and liver abscess. Emergent

laparotomy with abscess drainage was performed. After operation, the patient recovered well and discharged. The final blood and pus cultures showed klebsiella pneumonia infection.

Discussion: The liver receives blood from both systemic and portal circulations. This increased susceptibility to infections. The three major forms of liver abscess, classified by etiology, are as follows: Pyogenic abscess, which is most often polymicrobial, accounts for 80% of hepatic abscess cases in the United States. Amebic abscess due to Entamoeba histolytica accounts for 10% of cases. Fungal abscess, most often due to Candida species, accounts for fewer than 10% of cases. The prevalence of pyogenic liver abscess in Taiwan is 17.59/100, 000. The characteristics of these patients had old age (median age 61 years), diabetes (33.3%), liver cirrhosis (10.4%), cholelithiasis(14.6%), and concomitant malignancy (13.9%). Pyogenic abscesses may be caused mainly by ascending biliary or portal tract sepsis and in lesser degree by superinfection of cysts or necrotic tissue, trauma or hematogenous dissemination. Nevertheless, in many cases (up to 25% of patients) no underlying cause is found and the disease is defined as cryptogenic. Klebsiella pneumoniae is the most common pathogen of pyogenic liver abscesses in Taiwan (2, 3, 5, 22), especially in GFPLA. This newly diagnosed diabetic patient presented with DKA and sepsis. She had no right upper abdominal pain, normal liver function test, no jaudice except fever. Until 2 days later, She suffered from severe abdominal pain because of the liver abscess rupture with peritonitis and pneuoperitoneum. She had no other abdominal lesion. Therefore, we should be highly alert to liver abscess when diabetic patient admitted due to sepsis without obvious focus on lung and urinary tract area. Liver echo and abdominal CT are helpful techniques in differential intrabdominal infection especially in liver and biliary tract infection.

PP-18 GLUCOSE HOMEOSTASIS DURING ACUTE EXPOSURE TO HIGH ALTITUDES: PERSONAL EXPERIENCE IN SOUTH AMERICA

CHUN-TING YEH, NAI-CHENG YEH, FENG- CHIEH YEN, KAI-JEN TIEN, CHWEN-YI YANG

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

PURPOSE: Many environmental factors in high altitude differs from low altitude, such as the partial pressure of oxygen in the breathed air, temperature, humidity and solar radiation. Human physiology encounters considerable variation in high altitude during short-term exposure. Here, we present the author’s personal experience of blood sugar homeostasis in status of acute exposure to high altitude.

METHOD: A 30 years old male without any systemic disease had a trip in Peru and Bolivia. Fasting sugar recored in Taiwan was all within normal limit (below 100mg/dL). The initial altitude is around 3800 meters while landing in South America, and the subject stayed above 3500 meters for five days. Portable blood glucose meters was corrected in Taiwan before travel.

RESULT: The fasting finger sugar recorded in the morning were all above 100mg/dL but below 126mg/dL (112-112-110-118-101mg/dL, fasting time over 8 hours) during acute exposure to high altitude. And the post-prandial finger sugar were all within normal limit (below 140mg/dL). No acute illness except mild high mountain sickness noted during the first two days.

CONCLUSION: Lowlanders acute exposure to high altitude may induce stress-related hormone and further result in high fasting sugar. However, better insulin sensitivity in status of mild hypoxia might contribute to stable post-prandial sugar. There are strong evidences that the high fasting sugar will become normal after long-term exposure to high altitude. And lots of studies reveled that lower fasting sugar, lower prevalence of diabetes and obesity in populations from high altitudes. Thus, understanding the mechanisms that regulate the lower fasting sugar in highlanders could lead to new therapeutics for impaired glucose homeostasis.

PP-19 WHAT NEXT IN PATIENTS WITH TYPE 2 DIABETES MELLITUS INADEQUATELY CONTROLLED WITH METFORMIN AND SULFONYLUREA? PIOGLITAZONE OR BASAL INSULIN?— FROM THE PERSPECTIVE OF RENAL FUNCTION CHANGE

1YU-HUNG CHANG, 1DER-WEI HWU, 1KUN-CHEN LIN, 1DAO-MING CHANG, 2LING-WANG AN, 3CHANG-HSUN HSIEH, 1YAU-JIUNN LEE

1Lee’s Endocrinology Clinic; 2Beijing Ruijing Diabetes Hospital; 3Division of Endocrinology and Metabolism, Department of Internal Medicine, National Defense Medical Center, Tri-Service General Hospital, Taipei, Taiwan

Background: Despite insulin-sensitizer and insulin itself have proved their efficacy in improving glycemic control, clinical outcome may be dissimilar via their pharmacological characteristics. The aim of this study is to compare the renal function change of add on pioglitazone versus basal insulin in type 2 diabetic patients who failed of sulfonylurea and metformin regimens.

Methods: Patients with type 2 diabetes mellitus (T2DM) who consecutively visited a diabetesspecific polyclinic been prescribed pioglitazone or basal insulin (i.e. detemir and glargine) for at least 2 years owing to failed of sulfonylurea and metformin control were included. Propensity score matching was used to identify well-matched groups in order to decrease potential baseline confounders. We use Cox-regression analysis to investigate the influence of pioglitazone and basal insulin to CKD progression.

Results: A total of 1002 (pioglitazone: 559, detemir: 264, glargine: 179) patients were included. After propensity score matching, there were 105 patients with matchable baseline characteristics in each group. During a 3.3-year follow up, while the pioglitazone group showed a greater A1C reduction as compared with the detemir group (-0.93% vs. -0.37%, p<0.05), the pioglitazone group showed a greater body weight increase as compared with the detemir group (2.1 kg vs. 0.8 kg, p<0.05). There was no significant difference in A1C or body weight change in the group comparisons of pioglitazone vs. glargine and glargine vs. detemir. In contrast of a subtle decrease of renal function in the basal insulin groups; the pioglitazone group demonstrated a benefit in preserving renal function. In addition, the cox-regression analysis indicated that patients with detemir or glargine had higher probability of CKD progression as compared with the pioglitazone group with a hazard ratio of 2.63 (95% C.I.: 1.79~3.88) and 3.13 (95%:C.I.:2.01~4.87), respectively.

Conclusion: Our study firstly showed that pioglitazone may be advantage in preserving renal function comparing basal insulin when as add on therapy for glycemic control.

PP-20 MEDULLARY THYROID CARCINOMA IN A PATIENT WITH HASHIMOTO’S THYROIDITIS

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

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

Medullary thyroid carcinoma (MTC) is a rare form of thyroid cancer. MTC has variable cytologic patterns that makes its cytological diagnosis difficult. We report a patient with Hashimoto’s thyroiditis and elevated carcinoembryonic antigen (CEA) level that was later diagnosed as MTC. A 82 year-old man with history of hypertension and stroke who was referred to our endocrinology clinic because of right thyroid nodule. Laboratory findings were suggestive of Hashimoto’s thyroiditis in euthyroid states. A right thyroid heterogeneous nodule of about 4cm in diameter was found on thyroid sonogram. Cytological examination of the right thyroid nodule demonstrated benign follicular cells. The patient was also found to have elevated serum CEA level, thus he underwent serial of work-ups such as esophagogastroduodenoscopy, colonoscopy and CT scan of chest and abdomen which showed no evidence of malignancy. During his 4 years of follow up, he had repeated cytological studies that all showed benign follicular cells and numerous lymphocytes. However, his CEA level increased from 14.4 ng/ml to 33.4 ng/ml (reference range <5 ng/ml). Because of the progressive elevation of CEA level and increased focal uptake of right thyroid during 18F-Fluorodoexyglucose Positron Emission Tomography (FDG-PET), calcitonin was checked under the suspicion of MTC, and a markedly elevated calcitonin level 696 pg/ml (reference range 2.0-18.2 pg/ml) was found. Biochemical studies to rule out the co-existence of hyperparathyroidism and pheochromocytoma were negative. The patient underwent total thyroidectomy and neck lymph node dissection. Histopathological examination confirmed the diagnosis of MTC. Post-operatively, his CEA level lowered to 3.59 ng/ml, and calcitonin decreased to 63.5 pg/ml.

Here, we highlighted the importance of considering MTC as a differential diagnosis in a patient presenting with an elevated CEA level. Thyroid nodules with increased focal uptake on FDG-PET scan are at higher risk of being malignant. Moreover, coexistence of Hashimoto’s thyroiditis might increase difficulty in cytological diagnosis of MTC.

PP-21 CLINICAL FEATURES OF METASTATIC NEUROENDOCRINE TUMOR OF THE THYROID GLAND

1PO CHUNG CHENG, 1SHU YI WANG, 2TA-JEN WU

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

Background: Neuroendocrine tumor describes a heterogeneous group of neoplasms with distinctive histology and behavior. The prevalence of neuroendocrine tumor is relatively low, and these neoplasms predominantly originate from the intestine, pancreas, or the lungs. Metastatic neuroendocrine tumor of the thyroid gland is uncommon and has been described in a limited number of case reports.

Methods: The clinical features of a metastatic neuroendocrine tumor of the thyroid gland are illustrated.

Results: A 52-year-old man visited the emergency room of Changhua Christian Hospital due to respiratory distress for one week. Computed tomography demonstrated thyroid neoplasms with mediastinal extension and tracheal compression. Thoracoscopic biopsy revealed neuroendocrine tumor with positive staining for synaptophysin, chromogranin-A, and thyroid transcription factor-1.

Conclusion: Metastatic neuroendocrine tumor of the thyroid gland is unusual and may imitate clinical features of thyroid cancer. However, metastatic thyroid neuroendocrine tumor should be distinguished from thyroid cancer because of significant differences in hormonal secretion and treatment modality. Early diagnosis and treatment of metastatic neuroendocrine tumor of the thyroid gland will likely improve the clinical outcome.

PP-22 CASE REPORT OF DM WITH TOES GANGREN WHICH WAS ASSOCIATED WITH UNUSUAL ETIOLOGY: MITOCHONDRIAL DISORDER

WEI-TSEN LIAO, MING-CHIEH TSAI, CHUN-CHUAN LEE

Division of Endocrinology & Metabolism, Department of Internal Medicine, Mackay Memorial hospital, Taiwan, R.O.C.

Clinically, many diabetic patients have large vessel complications such as peripheral artery disease(PAD). It is a long and chronic course since atherosclerosis is the main etiology. If there is an atypical disease course, a rare etiology should be considered.

A 41-year-old woman was diagnosed with diabetes mellitus during hospitalization of metabolic acidosis on Jul. 2014. Six months later, she was admitted to ICU due to lactate acidosis(pH 6.8, Lactate 239 ng/dL) with respiratory decompensation, and bilateral toes gangrene developed within 2 days. After 4-days intensive treatment, she was transferred out of ICU.

Hyperlactatemia persisted(21.6 ng/dL) despite stable hemodynamics and oxygenation. Investigation of DM etiology showed high HbA1c(9%) with low BMI(14.7) but negative finding on T1DM antibodies, glucagon test or DM related hormone. Patient was short stature. Hearing loss was found since 20 years ago and mental slowing occurred since 1 year ago. These findings prompted us to survey mitochindrial disorder. Skeletal muscle biopsy showed red ragged fibers. Mitochondrial DNA analysis revealed A-to-G point mutation at position 3243. CT angiography did not show PAD. Autoimmune vasculitis markers were negative but tests of lupus anticoagulants were positive on Jan. 2015 and Jun. 2015. Toes gangrene may be associated with mitochondrial angiopathy or antiphospholipid syndrome. After Q10 and clopidogrel administration, serum lactate level decreased and autoamputation of toes gangrene occurred without any new ischemic lesion.

The expression of mitochondrial disease is variable. Because the mitotic segregaion and heteropasmy result in the different percentage of mutated mtDNA in every cell. We reported a case of DM with toes gangrene underlying mitochondrial disease. The gangrene can be explained by mitochondrial angiopathy. But the clinical data also meets APS. It is difficult to rule out APS because the APS may cause gangrene, and the oxidant mediated injury of APS may deteriorate mtDNA mutation.

PP-23 PROGNOSTIC MARKER OF DIABETIC NEPHROPATHY: A PILOT STUDY BY METABOLOMIC APPROACH

1CHIEN-AN CHOU, 1SZU-TAH CHEN, 2CHIA-NI LIN

1Division of Endocrinology and Metabolism, Department of Internal Medicine, Chang Gung Memorial Hospital, Chang Gung University, Taoyuan, Taiwan, R.O.C.; 2Department of Laboratory Medicine, Chang Gung Memorial Hospital Linkou Branch, Taoyuan, Taiwan

Background. Diabetic nephropathy (DN) is the leading cause of ESRD, but few biomarkers of DN are available. Although biomarkers such as serum creatinine and estimated glomerular filtration rate, eGFR) are used to categorize stage of chronic kidney disease (CKD), they could not predict prognostic outcome of renal function. In order to find a more sensitive surrogate prognostic marker for CKD progression, we conducted this study by analyzing plasma metabolomics from patients with different stages of CKD.

Design and methods. From September 2013 to September 2015, 49 diabetic patients with various stage of CKD were enrolled. Total of 186 metabolites including 40 acylcarnitine, 21 amino acids, 19 biogenic amines, 15 sphingomyelins and 90 glycerophospholipids were examined with UPLC/MSbased Absolute IDQ p180 kit. All metabolites were corrected between initial CKD staging and plasma concentration by Kruskal-Wallis one-way ANOVA. Events of advancing CKD stage and deterioration in eGFR and UACR in CKD stage 3 patients within 12 months’ interval were analyzed by Chi-square and Mann-Whitney U-test, respectively.

Results. 12 metabolites were significantly different (5 increased and 7 decreased, P<0.05) in advanced (stage 45) CKD. By using the mean value (m45x) of each of the 12 metabolites, tryptophan (P=0.006) and t4-OH-Pro (P=0.036) were found to be associated with events of renal function deterioration in CKD stage 3 patients with their index metabolite(s) levels below m45x. However, no significant difference were noted when the numerical change of eGFR and UACR were compared (tryptophan, P=0.052; t4-OH-PRO P=0.126).

Discussion. 12 metabolites (including C4, C5, Cit, Kynurenine, T4-OH-PRO, Ala, Lys, Met, Ser, Trp, Tyr, and Val) showed significant difference in advanced CKD. Tryptophan, by showing significant difference and borderline significance (P=0.006 and P=0.052) in dogmatic classification of CKD stage and continuous change in eGFR, may be regarded as a potential prognostic surrogate marker for CKD. This difference may be contributed to the limited patient number and follow up time in this study.

Key words: Diabetic nephropathy, Biomarker, Metabolites

PP-24 THE BIOCHEMICAL VARIANT BETWEEN DIFFERENT GENDERS IN PEOPLE AGED 40 TO 50 YEARS WHO HAVE NON-ALCOHOLIC FATTY PANCREAS DISEASE (NAFPD)

YI-HSUAN CHEN, CHIH-YUAN WANG

Division of Endocrinology, Department of Internal Medicine, National Taiwan University, 7, Chung-Shan South Road, Taipei, Taiwan

Background: Coronary heart disease risk is higher in male in the middle-aged group and visceral obesity is a key factor related to the cardiovascular risk. Fatty infiltration of pancreas could be viewed as visceral obesity. In the previous study, the prevalence of fatty pancreas is especially higher in male aged between 40-49 years than in females in the same age population, which may explain the discrepancy of cardiovascular risk in different genders. In this article, we would like to see if there is other biochemical variant in addition to visceral obesity between different genders aged 40 to 50 years.

Method: We enrolled total 307 NAFPD subjects (male: N= 219; female: N= 88) that were aged between 40 to 50 years. NAFPD was diagnosed by abdominal sonography. Biochemical parameters were compared between male and female groups by using Student’s t-test (Sigmart plot 15.0).

Results: The analysis revealed no specific difference in blood glucose level (AC, PC, and HbA1C) between females and males with NAFPD aged between 40~50 years. The level of total bilirubin, direct bilirubin, ALP, and GGT were significantly higher in male group (p< 0.001).

Conclusion: Male aged between 40 to 50 years with NAFPD has higher cholestasis risk than women in the same population. Further study is needed to identify if there is also significant difference of cholestasis risk in people aged 40~50 years without NAFPD, and if the discrepancy disappears in other age groups.

PP-25 A COHORT STUDY ON TEN-YEAR SURVIVAL OF SPORADIC MEDULLARY THYROID CARCINOMA WITH SOMATIC RET MUTATION: A SINGLE CENTER EXPERIENCE

1LI-LUN CHUANG, 3,8DAW-YANG HWANG, 4KUN-BOW TSAI, 5,7HON-MAN CHAN, 6,7FENG-YU CHIANG, 2,7PI-JUNG HSIAO

1Division of Endocrinology and Metabolism, Kaohsiung Municipal CiJin Hospital; 2Division of Endocrinology and Metabolism, Kaohsiung Medical University Hospital; 3Division of Nephrology, Kaohsiung Medical University Hospital; 4Department of Pathology, Kaohsiung Municipal Siaogang Hospital; 5Department of Surgery, Kaohsiung Medical University Hospital; 6Department of Otolaryngology-Head and Neck Surgery; 7School of Medicine, College of Medicine, Kaohsiung Medical University; 8Lipid Science and Aging Research Center, Kaohsiung Medical University

OBJECTIVE: Somatic RET mutations are reported in 40-50% of sporadic medullary thyroid carcinoma (sMTC) patients with prognostic significance. As it lacked somatic RET mutation reported previously for Taiwanese, we tried to assess the presence of somatic RET mutations and evaluate the potential outcome predictors for our sMTC patients.

METHODS: We collected data from seven sMTC patients from 1997 to 2005 and analyzed their clinic-pathological features up to 2015. All patients were still alive to follow up for 11~18 years. Tumor DNAs were extracted to assess exons 10-11 and 13-16, and the intron-exon boundaries of the RET gene.

RESULTS: Six cases (86 %) were screened positive of somatic RET gene mutations in hotspot regions, one at M918T, one at C620R and three at C634S with another two rare mutations at L629Q and V642I.

CONCLUSION: Comparing the current TNM staging system, the 10-year survival outcomes for our sMTC patients was not predicted by serum calcitonin and/or CEA, surgical extent, and presence of the somatic RET gene mutations. The small cohort demonstrated a relatively good outcome of sMTC patients to survive greater than 10 years. In addition, intensive treatment with total thyroidectomy with extensive neck lymph node dissection seemed to be the critical determinant of better survival outcome for sMTC patients.

PP-26 RELATIONSHIP BETWEEN METABOLIC PARAMETERS AND TESTOSTERONE LEVEL IN MALE PATIENSTS WITH T2DM -A CROSS-SECTION STUDY IN REGIONAL HOSPITAL

1SHIH-MING CHUANG, 1MING-NAN CHIEN, 1CHUN-CHUAN LEE, 2KAT-YIEN NGU

1Division of Endocrinology and Metabolism, Department of Internal Medicine, Mackay Memorial Hospital, Taipei; 2Division of Endocrinology and Metabolism, Department of Internal Medicine, Mackay Memorial Hospital, Taitung,

Introduction: Type 2 diabetes is associated with low testosterone (LT) identified in several observation studies and systemic analyses. Besides, LT was also associated with insulin resistance and subsequent risk of developing DM. Routine serum testosterone was rare utilized and not for screeing all diabetes patients. We try to investigate what kind characteristics of LT in patients with T2DM.

Methods: This cross-section study collected 80 men with T2DM who have visited our clinics. On the basis of serum testosterone level, patients were divided into two groups: LT group (serum testosterone less than 300ng/dL, n=26) and NT(normal testosterone)(testosterone more than 300ng/ dL, n=54). Body mass index(BMI), waist circumstance, glucose and lipid profiles, as well as liver and kindey function, albumin excretion rate were assessed in 3 months during testosterone measurement.

Results: Our patients with diabetes have overweight in BMI and one-third of which is correspond with LT group. Compared with the NT group, LT groups were with significantly higher triglyceride(TG) level and TG/HDL ratio. Other parameters such as fasting and postpranil glucose, glycated hemoglobin, total cholesterol, liver and kindery function, AER were not significant different in both groups. Elder patients (age>65 years) have higher prevelance of LT than younger patients. There is no significant difference in lipid and glucose profile between NT and LT group in elder patients. However, younger patients have higher TG and TG/HDL ratio.

Conclusions: In our investigation study, T2DM with LT was possibly associated with hyperlipidemia, especially high TG and TG/HDL ratio, in younger patients.

PP-27 HYPOGLYCEMIA AND INSULINOMA

CHIH-HUANG CHIU, SHU-YI WANG

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

The patient is a 36-year-old Minnan Taiwanese woman without systemic disease before. She suffered from spontaneous consciousness change for 10-20 minutes(1/3-4 months) and recover rapidly about 2-3 years. Cold sweating, hand tremor and hand tremor was noted at meantime. After pregnancy, The episode became frequently.

Lab data showed HbA1c 3.7%, TSH 0.79μIU/mL, Cortisol 12.06μg/dL, C-Peptide 2.87ng/mL, when Glucose 36mg/dL, Insulin 1.81μIU/mL. we arranged 72 hr Fasting test and lab data showed Insulin: 5.21, Glucose: 43, insulin/Glucose ratio: 0.12, Cortisol (Blood, AM) 6.93. After general condition stable, Abdominal MRI was arranged and revealed Nodular tumor at pancreatic tail. Due to recurrent hypoglycemia, neuroendocrine tumor (insulinoma) is considered. Pancreatic tail tumor s/p Laparoscopic Distal Pancreatectomy on (2014-2-17). Pathology showed grade 1 neuroendocrine tumor of pancreas (PT2N0Mx). After operation, no recurrent spontaneous consciousness change was noted again.

PP-28 ACROMEGALY PRESENTING WITH NEWLY-DIAGNOSED DIABETES MELLITUS: A CASE REPORT

PO-WEN YANG

Department of Internal Medicine, Keelung Hospital, Ministry of Health and Welfare, Taiwan, R.O.C.

Introduction: Acromegaly is characterized by excessive production of growth hormone (GH) and insulin-like growth factor-1 (IGF-1). Pituitary GH-secretion adenoma is the major cause of acromegaly. Diabetes mellitus may develop in patients with acromegaly. Case report: A 56-year-old man presented for a second opinion for the treatment of his newly-diagnosed diabetes mellitus. He reported weight loss and polyuria for 6 months. He weighed 71 Kgs and his height was 168 cm. His blood pressure was 130/90 mmHg. He had deepened voice, enlarged hands and feet, and prominent forehead and jaw as compared to his old picture on the health insurance card. His fasting blood glucose was 300 mg/dl, and HbA1C was 12.8%. Baseline screening test for acromegaly showed elevated GH (21.850, reference range 0.003-0.971 mg/ml), and elevated IGF-1 (1015, reference range 81 - 225 ng/ ml). Skull lateral view disclosed ballooning of sella turnica. Magnetic resonance imaging of the sella revealed a homogeneously enhancing lesion involving the pituitary gland measured about 12 mm in height, suggestive of a pituitary macroadenoma. Conclusion: Acromegaly may present with newdiagnosed diabetes mellitus. A detail physical examination and review of an older photograph are clues in examining a patient suspected of having acromegaly.

PP-29 USE MODERN THERAPY IN A 69-YEAR-OLD COMPLICATED PATIENT WITH TYPE 2 DIABETES: A 2-YEAR EXPERIENCE

SHENG-CHI SU

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

Introduction: American Diabetes Association published Standards of Medical Care in Diabetes in Diabetes Care annually. The guidelines provide health care providers with all components of diabetes care, general treatment goals, and tools to evaluate quality care.

I set glycemic target for new patients with diabetes by patient/disease features in guideline first.

The guidelines use metformin as first-line medication after healthy eating, weight control, increased physical activity, and diabetes education.

According to drug efficacy, hypoglycemic risk, weight effect, side effects and costs, the guidelines suggest 6 kinds of medication for secondary-line choose after 3 months of monotherapy.

I used homeostatic model assessment (HOMA) index as drugs adjustment tools

It can evaluate severity of insulin resistance and relative beta-cell function by fasting glucose and insulin.

I think HOMA index as a good tool in clinical practice.

Case Report: A 67-year-old female visited Endocrinology clinic for hyperglycemia and frequent urine tract infection on 2013/11/5.

In her past history, Diabetes was diagnosed on 2008 and She took sulfonylurea and metformin. HbA1c was 10.4% on 2008，10.8% on 2009. Frequent urine tract infection was noted and she visited urologic clinic regularly. She loss follow-up until 2013/6/19.

She was admitted to our medical ward due to urine tract infection with fever on 2013/6/19~2013/6/24. After discharge, she took 3 kinds of oral anti-diabetic agents (sulfonylurea, metformin and D PP-4 inhibitor) for sugar control. Hypertension was diagnosed at admission and she took fixed-dose ARB/CCB for blood pressure control. Later A1c showed 8.4% on 2013/7.

She visited our ER due to urine tract infection with fever on 2013/11/4. She was referred to my clinic for sugar control.

I added sulfonylurea dose for it but hypoglycemia (ac sugar: 65 mg/dl on 2013/11/26) was noted. At this exam, hyperlipidemia was noted and I used statin for it.

Then I decreased sulfonylurea dose and use fixed dose DPP4 inhibitor and extended release metformin. HbA1c decreased to 7.2% but elevated to 8.0% on 2014/9. I checked fasting glucose and insulin since 2015/1.High insulin resistance and insulin level was found and I decreased her sulfonylurea dose and add metformin dose.HbA1c was improving to 6.8% without hypoglycemia.

Discussion: According to patient/disease features in Standards of Medical Care in Diabetes in Diabetes Care，Her glucose target sets less stringent (<8%). But I used HOMA index for evaluating insulin resistance and relative beta-cell function. It can help me to improve glucose control with low hypoglycemic risk. It can be a good tool for health care providers.

References:

1. Standards of Medical Care in Diabetes in Diabetes Care, 2016 2. Homeostasis model assessment: insulin resistance and beta-cell function from fasting plasma glucose and insulin concentrations in man. Diabetologia 28:412–419, 1985 3. Analysis of homeostasis model assessment-insulin resistance HOMA-IR in healthy young Chinese adults, Saudi Med J. Saudi Med J 2010 Dec; 31(12):1375-6.

PP-30 DIPEPTIDYL PEPTIDASE-4 INHIBITOR PREVENTS ARTERIAL DAMAGE THROUGH STRA6 SIGNALING BEYOND GLYCEMIC CONTROL IN HIGH FAT DIET-FED MICE

1CHAO-HUNG CHEN, 2HSING-YI LIN, 2KUN-DER LIN, 2MEI-YUEH LEE, 2YU-LI LEE, 2WEI-WEN HUNG, 2HE-JIUN JIANG, 2,3PI-JUNG HSIAO, 2,3SHYI-JANG SHIN

1Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, 80708, Taiwan; 2Division of Endocrinology and Metabolism, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, 80708, Taiwan; 3Department of Internal Medicine, School of Medicine, College of Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, 80708, Taiwan

We recently found that O-GlcNAcosylation of RBP4 receptor (STRA6) with a decrease of RBP4 binding activity suppressed CRBP-1 and RARα expression and thereafter activate apoptosis and fibrosis in high-glucose cultured renal cells and in the kidneys of diabetic mice. Dipeptidyl peptidase-4 inhibitors (DPP-4i) was reported to capably ameliorate kidney fibrosis in diabetic mice. We hypothesized that DDP-4i can produce its pleiotropic action to prevent arterial damage beyond glycemic control.

STRA6, CRBP1, RARα, LOX-1, caspase 3, collagen 1 and fibronectin was measured by Western blot analysis for protein and PCR for mRNA expression in the aorta in normal fat diet(NFD)-fed, high fat diet(HFD)-fed mice and sitaglitipin-treated HFD-fed mice. We aimed to investigate whether the recipR.O.C.al appearance of STRA6 cascade down-regulation and fibrosis increase in the aorta of HFD-fed mice, and whether DPP4i reverses these alterations beyond glycemic control..

The expression of STRA6, CRBP1 and RARα protein and mRNA expression remarkably decreased, while caspase 3, collagen 1, and fibronectin significantly increased in the aorta of HFD-fed mice as compared with NFD-fed mice. All these changes in the aorta of HFD-fed mice were reversed in sitaglitipin-treated HFD-fed mice. The blood glucose values in HFD-fed mice and sitaglitipintreated HFD-fed mice are not different, but are higher than NFD-fed mice.

We conclude that DDP-4 inhibitor can produce its beneficial action to prevent HFD-induced fibrosis and apoptosis in arteries of HFD-treated mice by reversing the suppression of RBP 4 receptor/ CRBP-1/RARα signaling beyond its glycemic control.

PP-31 BASELINE FACTORS ASSOCIATED WITH BETTER RESPONSE TO INSULIN LISPRO LOW MIXTURE OR INSULIN GLARGINE IN DURABLE STUDY

1THOMAS LEW, 2NAN JIA, 3ANGEL RODRIGUEZ, 4ZBIGNIEW KINDRACKI

1Presenting on behalf of Eli Lilly and Company, Indianapolis, USA; 2Eli Lilly and Company, Indianapolis, USA; 3Eli Lilly and Company, Alcobendas, Madrid, Spain; 4Eli Lilly Poland, Warsaw, Poland

BACKGROUND: Identification of patient characteristics associated with better efficacy and safety outcomes may help clinicians in their choice of therapies. This analysis is to determine the major baseline factors associated with better efficacy and safety response for insulin lispro low mixture (LM) or insulin glargine (IG) in insulin-naïve patients with type 2 diabetes (T2D) using data from a randomized clinical trial (DURABLE Study).

METHODS: Baseline covariates were used to build their nonparametric model with the efficacy and safety outcomes via the gradient boosting method (GBM). Hypothetical outcomes were calculated via this model, and treatment differences were calculated when patient was assigned to LM compared with IG. Further assessments were made to select the top baseline covariates that distinguish the greatest treatment differences. Analyzed baseline factors included baseline HbA1c, fasting blood glucose (FBG), age, body mass index (BMI), weight, duration of diabetes (DoD), and oral antidiabetic drugs use.

RESULTS: This study database includes 2203 insulin-naïve patients with T2D (1102 randomized to IG and 1101 to LM). Based on the GBM, the top baseline covariates associated with the greatest treatment differences (and their relative influences) at the end of 26 weeks’ treatment are: for change in HbA1c: FBG (30.78%), age (29.66%), HbA1c (19.45%); for achieving HbA1c target of <7%: BMI (28.38%), age (23.73%), weight (23.39%); for weight change: weight (21.30%), HbA1c (19.54%), DoD (15.56%); for self-monitored FBG before morning meal: FBG (42.16%), age (17.82%), HbA1c (14.73%); for hypoglycemia frequency since last visit: FBG (50.64%), BMI (16.67%), weight (12.40%); and for hypoglycemia rate per 30-day period since last visit: FBG (56.54%), weight (12.77%), BMI (11.4%). Overall, LM shows superiority over IG in change in HbA1c and achieving HbA1c target, whereas IG shows superiority over LM in the other endpoints.

CONCLUSIONS: This analysis identified baseline covariates that may predict potential treatment differences between LM and IG for the same patient. These results may help clinicians at insulin therapy initiation.

DISCLOSURES: This study was supported by Eli Lilly and Company, Indianapolis, IN, USA. This is an encore of an abstract presented at the International Diabetes Federation – 23rd World Diabetes Congress, 30 November – 4 December 2015; Vancouver, Canada.

PP-32 ASSOCIATION BETWEEN MILD AND SEVERE HYPOGLYCEMIA IN PATIENTS WITH TYPE 2 DIABETES INITIATING INSULIN

1THOMAS LEW, 2ADREAS FESTA, 2RAN DUAN, 2HAODA FU

1Presenting on behalf of Eli Lilly and Company, Indianapolis, USA; 2Eli Lilly and Company, Indianapolis, USA

BACKGROUND: The relationship between mild (MH) and severe hypoglycemia (SH) has been quantitatively evaluated in a randomized, controlled, open-label, 2-arm, parallel study in 2008 patients with type 2 diabetes initiating insulin (insulin glargine or insulin lispro mixture 25/75).

METHODS: Standard definitions were used for MH (all non-SH) and SH. A Cox regression model was employed to identify risk factors associated with incident SH.

RESULTS: Average age was 56.90 (9.82) years, diabetes duration was 9.54 (6.10) years, body mass index was 31.68 (5.96) kg/m2 and HbA1c was 9.03 (1.26) %. During a treatment period of 24 weeks, 78.6% (1606/2043) of the patients experienced more than one MH, but no SH, with a mean monthly MH rate (SD) of 2.67 (2.98). Thirty-three of 2043 patients (1.6%) experienced at least one SH, with a mean monthly MH rate (SD) of 5.11 (3.98).

CONCLUSIONS: Among all factors tested in the model, only the monthly MH rate (hazard ratio 1.174; confidence interval, 1.106–1.248; p<.0001) was significantly associated with SH. Stratification in high and low rates of MH showed that the risk of SH was significantly lower (p<.0002) for the low MH-rate group (MH rate ≤1.05) compared to the high rate group (MH rate ˃1.05).

DISCLOSURES: This study was supported by Eli Lilly and Company, Indianapolis, IN, USA. This is an encore of an abstract presented at the American Diabetes Association – 74th Annual Scientific Sessions, 13 – 17 June 2014; San Francisco, California.

PP-33 IMPROVEMENT IN HBA1C IN PATIENTS WITH TYPE 2 DIABETES MELLITUS TREATED WITH ONCE-WEEKLY DULAGLUTIDE ACROSS BASELINE BODY MASS INDEX SUBGROUPS AT 26 OR 52 WEEKS

1THOMAS LEW, 2LUIS ALBERTO VÁZQUE, 3ESTEBAN JÓDAR, 4CARLOS TRESCOLI, 5CLAUDIA NICOLAY, 2JESÚS REVIRIEGO, 6RAFFAELLA GENTILELLA

1Presenting on behalf of Eli Lilly and Company, Indianapolis, USA; 2Eli Lilly, Alcobendas, Spain; 3Hospital Universitario Quirón, Madrid, Spain; 4Hospital Universitario de la Ribera, Alzira, Valencia, Spain; 5Lilly Deutschland GmbH, Bad Homburg, Germany; 6Lilly Diabetes, Eli Lilly Italia, Sesto Fiorentino, Italy

BACKGROUND: This post-hoc analysis investigated the efficacy of dulaglutide and active comparators across baseline body mass index (BMI) categories (BMI <30, ≥30 to <35 or ≥35kg/ m 2) in patients with type 2 diabetes mellitus (T2DM) using data from the Phase 3 randomized trials AWARD-1 to -6.

METHODS: Patients with T2DM received dulaglutide [1.5 mg, n=1719 (AWARD-1 to -6); 0.75 mg, n=1417 (AWARD-1 to -5)], or exenatide (n=276), insulin glargine (n=558), metformin (n=268), sitagliptin (n=315) or liraglutide (n=300), in addition to other concomitant background treatments. Analysis of covariance models (AWARD-1 to -5) or mixed-effects model for repeat measures (AWARD-6), including treatment-by-BMI subgroup interaction terms, were applied by study to estimate the effect of each treatment on HbA1c at 52 weeks (AWARD-1 to -5) or 26 weeks (AWARD-6) and to compare dulaglutide and corresponding active comparators for patients with baseline BMI <30, ≥30 to <35 or ≥35kg/m2 (intention-to-treat population).

RESULTS: Baseline mean BMI in each study ranged from 31.2 to 33.6 kg/m2. HbA1c reductions from baseline according to BMI subgroup were recorded for each study. In all studies, dulaglutide 1.5 mg, dulaglutide 0.75 mg and all active comparators achieved statistically significant HbA1c reductions from baseline overall and in all BMI subgroups. No statistically significant treatment-by-BMI subgroup interactions were found for reductions in HbA1c.

CONCLUSIONS: Dulaglutide (1.5 mg or 0.75 mg) is an effective treatment for patients with T2DM, regardless of baseline BMI. There was no evidence of any treatment-by-BMI subgroup interaction for HbA1c change, suggesting that baseline BMI had no effect on the relative antihyperglycemic efficacy associated with dulaglutide versus comparator antidiabetes agents.

DISCLOSURES: This study was supported by Eli Lilly and Company, Indianapolis, IN, USA. This is an encore of an abstract presented at the European Association for the Study of Diabetes, 51st Annual Meeting, 14 – 18 September 2015; Stockholm, Sweden.

PP-34 COMPARISON OF EFFICACY AND SAFETY OF TWO STARTING INSULIN REGIMENS IN NON-ASIAN, ASIAN INDIAN, AND EAST ASIAN PATIENTS WITH TYPE 2 DIABETES: A POST-HOC ANALYSIS OF THE PARADIGM STUDY

1L JI, 2KW MIN, 3J OLIVIERA, 4T LEW, 5R DUAN

1Peking University People’s Hospital, Beijing, China. 2EULJI Hospital, Seoul, Republic of Korea. 3Takeda Pharmaceuticals, San Diego, USA. 4Eli Lilly and Company, Taipei, Taiwan. 5Eli Lilly and Company, Indianapolis, USA.

OBJECTIVE: To examine differences between three racial/ethnic subgroups of insulin-naïve patients with type 2 diabetes (T2D) regarding initiation and intensification of insulin therapy with insulin lispro mix 25 (25% insulin lispro, 75% insulin lispro protamine suspension [LM25]) or insulin glargine plus insulin lispro (G+L).

METHODS: This post-hoc analysis of a multi-country, randomized, open-label, active-controlled study focused on non-Asian (n=130), Asian Indian (n=106), and East Asian (n=89) patients taking oral antidiabetic medications (metformin plus sulfonylurea and/or pioglitazone) without insulin for ≥90 days who demonstrated inadequate glycemic control (HbA1c ≥7.0% [≥53 mmol/mol] and <11.0% [<97 mmol/mol]).

RESULTS: HbA1c reductions were reported in all subgroups: non-Asian (LM25, 2.07%; G+L, 2.05%), Asian Indian (LM25, 1.75%; G+L, 1.60%), and East Asian (LM25, 2.03%; G+L, 1.76%); Asian Indians and East Asians recorded higher HbA1c values at endpoint than non-Asians. A higher percentage of non-Asians (LM25, 51.7%; G+L, 48.1%) achieved HbA1c <7% than Asian Indians (LM25, 43.2%; G+L, 29.2%) and East Asians (LM25, 37.5%; G+L, 36.1%), although differences were not statistically significant (p=0.12; p=0.06, respectively). Mean total daily insulin dose (U/kg) was non-Asian (LM25, 0.67; G+L, 0.61), Asian Indian (LM25, 0.91; G+L, 0.90), and East Asian (LM25, 0.53; G+L, 0.59). Ratio of mealtime to total insulin dose in G+L arm was non-Asian: 0.19±0.23, Asian Indian: 0.33±0.25, and East Asian: 0.34±0.27. Overall incidence (%) of hypoglycemia was non-Asian (LM25, 94.1; G+L, 91.8), Asian Indian (LM25, 90.4; G+L, 88.5), and East Asian (LM25, 69.8; G+L, 77.3).

CONCLUSIONS: Despite greater insulin use, Asian Indians reported the least HbA1c reduction. Similar HbA1c reduction was seen in East and non-Asians, with a lower hypoglycemia rate. Greater mealtime insulin coverage was required by Asians than non-Asians. These findings highlight the importance of considering ethnicity in insulin treatment decisions for T2D patients