ACTA ENDOCRINOLOGICA (BUC)

years because of their cardio-protective and renoprotective properties in diabetes. SGLT-2 inhibitors, when introduced in diabetic patients, may cause euglycemic diabetic ketoacidosis. A 55-year-old woman presented with low-grade fever, vomiting, and lethargy. She was started on dapagliflozin two years back. On workup, she was diagnosed with euglycemic diabetic ketoacidosis (EDKA) and was managed accordingly. She improved clinically while her dapagliflozin was stopped. With a literature search, we have identified 15 case reports of EDKA with dapagliflozin since 2015. There are no standard guidelines regarding the monitoring of patients for this rare but potentially morbid complication. Moreover, the exact mechanism for this is unknown. Various precipitating factors are linked with SGLT-2 inhibitors in promoting EDKA. We recommend that customary plans should comprise educating the patient about this rare complication before commencing medication, close follow-up with serial electrolyte monitoring, and discontinuing medications in the state of infection, dehydration and recent surgery and serious illness requiring hospitalization.

Context. Polycystic ovary syndrome (PCOS) or disease (PCOD) is one of the most common causes of female infertility. Objective. The objective of this study was to find out the influence of insulin on LH, testosterone and SHBG in diffrent PCOS categories. Experimental design. A total of 800 women who were subjected to infertility treatment at infertility clinics were selected. About 60 healthy females with regular menstrual cycles were considered as control. The data were collected from hospital records using subject’s consent. Results. Relationship of insulin to LH and testosterone was positive and significant (p<0.05) in the entire PCOS group and in five PCOS subcategories with increased LH rise (i.e. 1.3, 2, 3, 4 & 5 times of LH rise in relation to FSH levels in each group respectively). The correlation pattern showed an increasing trend from lower to increased rise of LH compared to FSH. The relationship between insulin and SHBG was negative and significant (p<0.05) in all PCOS subcategories, except for the group having similar LH and FSH levels and also in another group with FSH levels higher than LH levels. A strong positive correlation was established between insulin and SHBG in normal subjects. The percentage of negative correlation was strong in PCOD subcategories with elevated rises of LH. Conclusion. This study established the influence of insulin on other marker hormones (LH, testosterone an SHBG) in various PCOS categories in view of their percentage of relationship.

Context. Sleeve gastrectomy is an effective method for management of obesity. The Bariatric Analysis and Reporting Outcome System (BAROS) is a comprehensive and standard system for the assessment of outcomes of weight loss surgery. It is consisted of weight loss, changes in obesityrelated comorbidities and quality of life measurements. We investigated results of the sleeve gastrectomy based on the BAROS. Material and Methods. Outcomes of laparoscopic sleeve gastrectomy surgery was studied in 45 patients with obesity (11 male, 34 female), after 45 months in Turkey. Results. Total weight loss was 26.4±0.1% of body weight at 45 months. Weight regain was seen in 97.8% of the patients with an average 14.5 kg and 13.7% body mass index points. The surgery caused 76% decrease in incidence of obstructive sleep apnea, 73% decrease in type 2 diabetes, 63% decrease in hyperlipidemia and 62% decrease in hypertension. Significant improvement is observed in all quality-of-life parameters. The final score of the BAROS was 4.23±1.02. Conclusion. Based on BAROS, sleeve gastrectomy provides significant improvements in weight loss, incidence of medical comorbidities and quality of life after surgery. Future studies should address prevention of weight regain after the surgery.

Background. Usually, silver stain is needed to differentiate between normal or hyperplastic hypophysis and pituitary adenomas. Many papers reported the lack of reticular fibers network as mandatory for pituitary adenoma diagnosis. \r\nAim. Differences between the architecture of reticular fibers in normal pituitary and pituitary adenomas \r\nMethods. Gordon- Sweet silver staining of pituitary specimens, prelevated during pituitary surgery performed in 138 patients with the endocrine and imagistic diagnosis of pituitary macro-adenomas. \r\nResults.Pituitary specimens of pituitary adenomas was confirmed in 133 cases; 3 specimens were with normal pituitary tissue, 1 with pituitary hyperplasia, 1 with pituitary apoplexy.Twelve of 133 pituitary adenomas specimens were associated also with normal pituitary tissue.There was a loss of acinar network of reticular fibres in 115 cases, but the present study describes the persistence of reticular fibers networks in 18 (13,53%) of 133 pituitary adenomas. We identified five distribution patterns of remanent reticular fibers network in pituitary adenomas using silver staining. \r\nIn conclusion, persistence of reticular fibers in a small number of pituitary adenomas could be a possible pitfall in the discrimination between the normal hypophysis and pituitary adenoma.

Background. Thyroid nodules are common; however, the association of two or more different tumors in the thyroid gland is unusual. We present a first case with the association of three histological types of thryroid tumors. To the best of our knowledge, this association has not been reported in the literature before. We aim here to highlight the possible coexistence of many lesions in the thyroid gland and to discuss treatment options. Case presentation. We report the case of a female patient who presented with a multinodular goiter. The final pathology after total thyroidectomy found the association of a multifocal papillary thyroid microcarcinoma arising within a Hurthle cells adenoma in a lobe and a noninvasive follicular thyroid neoplasm with papillary nuclear features in the other lobe. Due to the very low risk of recurrence, the patient was not treated with radioactive iodine. Conclusions. Many controversies remain about the management of Hurthle cells tumors and many variants of papillary thyroid carcinoma. Although the management of our case did not change, more studies are necessary to analyze the evolution of patients with multiple thyroid neoplasms. When discussing therapeutic options, the advantages and disadvantages should be considered case by case based on disease staging.

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Lingual thyroid is a rare developmental disorder, and it is the result of failure of the thyroid gland to descend from the tongue root to its normal site. The ectopic thyroid with a functioning gland is even rarer. In this case, we present a 44-year-old female patient with a complaint of foreign body sensation, progressive dysphagia and dyspnea due to ectopic thyroid tissue. Her complaints were totally resolved after L-thyroxine treatment. Here we report a patient with functioning ectopic thyroid tissue who had had bilateral subtotal thyroidectomy 10 years ago due to multinodular goiter. In conclusion, if progressive\r\ndysphagia, dyspnea, and foreign body sensation occurs in a patient who had thyroidectomy and living in an endemic goiter region, lingual thyroid may be underlying disorder.

Hyperinsulinism/hyperammonemia (HI/HA) syndrome is caused by activating mutations in GLUD1 gene, and causes fasting as well as protein sensitive symptomatic hypoglycemia, in addition to persistently elevated plasma ammonia levels. First-line treatment is diazoxide, and most patients respond well to this agent, however side effects may be observed. The most frequent side effect of diazoxide is fluid retention and hypertrichosis, while hyperuricemia and hematologic side effects are observed less often. Herein, we report a case who had a heterozygous mutation of GLUD1 gene and who developed diazoxide related neutropenia 8 years after the start of treatment. On follow-up, leucopenia and mild neutropenia persisted and the treatment was changed to somatostatin analogues. However, she developed persistent severe symptomatic hypoglycemia and required diazoxide retreatment. A lower dose of diazoxide (6 mg/kg/day) successfully controlled hypoglycemia and cell counts increased even though they were not normalized. Neutropenia in current case presented after a long period of time of diazoxide use and this period is the longest defined in the literature. Long-term endocrine and hematologic follow-up of this patient up to 18 years old will also be presented.

Background. The purpose of this study was to observe the effects of denosumab on bone mineral density (BMD), bone turnover markers and serum calcium in patients with primary hyperparathyroidism (PHPT) and osteoporosis. Methods. Seven consecutive patients with PHPT were administered a single subcutaneous injection of denosumab, 60 mg. The subjects were followed up to 6 months: serum calcium on days 1,3,7,14,30 and at 3 months and 6 months; serum intact parathyroid hormone (iPTH), C-telopeptide (CTX) and N-mid osteocalcin at baseline, 3 months and 6 months. BMD by DXA, at the femoral neck (FN) and lumbar spine (LS), were measured at baseline and at 6 months. Results. The patients (mean age= 69.8 yrs, range 62-81) had mild PHPT (mean total calcium = 10.8 mg/dL; mean PTH = 148.9 pg/mL); all had osteoporosis and four were currently treated with various bisphosphonates (BP). After 6 months mean LS BMD increased significantly by 4.5 % (p = 0.04) and mean FN BMD by 2.4% (p= 0.09 two-tailed; p = 0.047 one-tailed). Serum CTX decreased significantly by 90% at 3 months (p = 0.04), and by 48% at 6 months (p = 0.02); the similar changes for serum osteocalcin were 41% and 42% (p = 0.07, onetailed), respectively. In the first two weeks, serum total Ca variably decreased vs. baseline (0.5 to 2.8 mg/dL) in six out of seven patients. After 6 months mean total serum Ca nonsignificantly increased vs. baseline (11.4 mg/dL vs. 10.8 mg/dL, p = 0.1). Serum iPTH levels did not significantly change at both 3 and 6 months; after 6 months there was a trend toward decreased values (p = 0.03 onetailed). Conclusion. Denosumab increased BMD at both lumbar spine and femoral neck, and significantly decreased bone resorption in patients with PHPT. The effects on hypercalcemia were mild and transient, with a numerical increase after 6 months.

Context. Hyperparathyroidism-jaw tumour (HPTJT) syndrome is a rare autosomal dominant cause of familial hyperparathyroidism associated with ossifying fibromas (OF) of the maxillofacial bones and increased risk of parathyroid carcinoma, caused by inactivating germline mutation of the cell division cycle 73 (CDC73) gene. Objective. To report the first Romanian family with HPT-JT and genetic screening of CDC73 gene. Subjects and Methods. Mutational analysis of the CDC73 gene and genetic screening of the family of a proband with HPT-JT. Histological diagnosis of parathyroid tumors (WHO criteria) and immunohistochemistry (parafibromin) were performed. Results. Three of the six screened family members had evidence of PHPT and surgically proven parathyroid tumours. Two of the three affected members had parathyroid carcinomas and one had two parathyroid adenomas. Genetic screening of CDC73 gene revealed that 4 of 6 patients showed a heterozygous germline deletion of one nucleotide: c.128-IVS1+1 delG. All the three affected patients, resulted to be carriers of the CDC73 mutation, but each one bearing a different CDC73 polymorphism. Conclusions. We identified a new CDC73 germline mutation in a Romanian family of HPT-JT. Analysis of clinical phenotypes in the four mutated individuals confirmed the incomplete penetrance and the variable clinical expression of the disease.