ACTA ENDOCRINOLOGICA (BUC)

We present a 18 year old phenotypic female patient who presented for primary amenorrhea. Pelvic ultrasound revealed a hypoplastic uterus and CT scan showed a hypoplastic right gonad and a left gonadal tumor with extrapelvic location. Karyotype was 46XY. Hormonal assessment indicated hypergonadotropic hypogonadism: FSH was 39.69 mUI/ml, estradiol was 28.07 pg/ml, testosterone was 0.17 ng/ml. DHEA level was high – 21 ng/ml. Gonadectomy was performed at 15 years and histologic examination diagnosed left gonadoblastoma and right teratoma in a dysgenetic gonad. The patient had a good postoperatory evolution. Menses were induced with estrogenic and then estroprogestogenic treatment. Plastic breast surgery was performed at 18 years. Establishing the genotypic sex in patients with primary amenorrhea represents a crucial step knowing that intersex disorders bearing Y chromosomal material have a high risk for gonadoblastoma and germ cell tumors.

Background. Congenital adrenal hyperplasia (CAH) is an autosomal recessive inherited disorder caused by congenital deficiency of enzymes involved in cortisol biosynthesis from cholesterol in the adrenal cortex. In this article, we aimed to present a 29-year-old female patient with I2 splice point mutation detected in one allele and P453S mutation on the other allele of CYP21A2 gene associated with 21-hydroxylase deficiency. Her further investigation revealed that her mother had P453S mutation and her father had I2 splice mutation. Case report. A 29-year-old woman with CAH was admitted to our clinic with the request of pregnancy. Her physical examination revealed a height of 151 cm, weight 59 kg, body mass index 25.8 kg/m2. According to Tanner staging, she had Stage 3 breast development and pubic hair. Her laboratory test results were as follows: Glucose: 79 mg/dL (70-100 mg/dL), Creatinine: 0.6 (0.5-0.95 mg/ dL), Sodium: 138 mEq/L (135-145 mEq/L), Potassium: 4.4 mEq/L (3.5-5.1 mEq/L), Cortisol: 0.05 μg/dL, ACTH: <5.00 pg/mL (5-46 pg/mL), 17-OH progesterone: 7.67 ng/mL (0-3 ng/mL). Chromosome analysis revealed a 46, XX karyotype. CYP21A2 gene mutation analysis was performed for the patient whose clinical history and laboratory results were compatible with congenital adrenal hyperplasia. During the reverse dot blot analysis, I2 splice mutation in one allele and P453S mutation in the other allele were detected. Conclusion. Although the I2 splice mutation detected in our case was mostly associated with a saltwasting form of CAH, it was thought that the other P453S mutation detected may explain the relatively good clinical course in our case.

Background. Adipose tissue is linked to cardiovascular and metabolic complications of diabetes by increased local production of adipokines that may lead to oxidative stress and endothelial dysfunction. Objective. The aim of the present study was to investigate the association between plasma adipokines levels and anthropometric and systemic endothelial dysfunction markers in obese type 2 diabetic patients. Materials and methods. Two groups of type 2 diabetic patients were selected considering their Body Mass Index (BMI) value: group 1, overweight (BMI= 28.4 -29.9 kg/m2; n = 35) and group 2, obese (≥30 BMI≤ 40 kg/m2; n = 45). In all patients there were assessed: height, weight, waist and hip circumference, visceral fat index, albumin/creatinine ratio (ACR), plasma levels of insulin, proinsulin, adiponectin and leptin. The HOMA-IR and waist to hip ratio (WHR)were calculated as well. Results. Comparing the obese diabetic patients with the overweight ones, plasma levels of leptin were higher (p<0.001) while adiponectin levels were lower (p<0.05). BMI was positively correlated with leptin (r=0.661, p<0.001) and negatively with adiponectin (r=-0.338, p=0.008). Moreover, leptin was positively correlated with the waist circumference (r=0.453, p<0.001), visceral fat index (r=0.555, p<0.001) and HOMA-IR (r=0.370, p=0.004) while adiponectin was negatively correlated with waist circumference (r=-0.350, p=0.006), visceral fat index (r=-0.269, p=0.038) and HOMA-IR (r=-0.318, p=0.013). We have also found positive correlation for ACR with HbA1c (r=0.549, p<0.001), glycemia (r=-0.411, p=0.001), HOMA-IR (r=0.445, p<0.001) and with leptin (r=0.276, p=0.033) and negative correlation with HDL-cholesterol (r=-0.304, p=0.018). Conclusions. Leptin and adiponectin, as indicators of chronic low grade inflammatory syndrome are involved in the pathogenesis of insulin resistance and endothelial dysfunction in obese type 2 diabetic patients.

Granulomatous hypophysitis is a very rare inflammatory lesion of the pituitary gland. Its typical clinical presentation is as an expanding sellar mass mimicking an adenoma, making it difficult to confirm the disease without a histopathological examination. Furthermore, determining the underlying etiology is a significant diagnostic challenge for clinicians. Case Report. We report the case of a 42-year-old female who presented with a history of severe headache and a sellar mass on imaging; she was initially diagnosed with an invasive pituitary adenoma but received a final diagnosis of granulomatous hypophysitis. The differential diagnosis was focused on idiopathic granulomatous hypophysitis versus tuberculous hypophysitis. On the one hand, the patient did not present signs of active tuberculosis nor of a systemic disease, and the PCR for mycobacteria on the pituitary tissue was negative; therefore, a diagnosis of idiopathic granulomatous hypophysitis would be appropriate. However, because the patient was proceeding from an endemic zone of tuberculosis and her Mantoux and QuantiFERON tests were positive, tuberculous hypophysitis could not be totally excluded. Conclusions. This case highlights the difficulties of correctly diagnosing granulomatous hypophysitis, even postoperatively, and the need to be aware of this rare entity when evaluating a pituitary enlargement in order to provide the most appropriate treatment.

Primary Hyperaldosteronism is one of the causes of secondary hypertension. Primary Hyperaldosteronism is characterised by an increase in the production of aldosterone and the inhibition of the secretion of renin. We described here a case with rhabdomyolysis and severe hypokalemia as a cause of primary hyperaldosteronism. The creatine kinase, aldosterone were very high. Cortisol values and midnight salivary cortisol values were within normal range. The patient had been under treatment for high blood pressure for more than six years, with ARBs and calcium channel blockers. During this time the potassium values measured frequently every year were below normal range, but primary hyperaldosteronism was not suspected.

Background. There are few data to demonstrate the usefulness of N-terminal pro B-type natriuretic peptide (NT-proBNP) for the left ventricular diastolic dysfunction (LVDD) diagnosis in metabolic syndrome (MSy) patients as the relationship between NT-proBNP and MSy components is still under study. Objectives. The present study aims to determine the influence of MSy components on NT-proBNP concentrations. In this respect, we tried to identify the relationship between NT-proBNP concentrations and LVDD in patients with MSy and preserved LV systolic function. Methods. 68 hospitalized obese patients with MSy (IDF2006 definition) were taken under study. All patients underwent Doppler echocardiography. NT-proBNP was determined using the ELISA method (Biomedica). The data obtained in the study group were compared to those of 70 obese subjects, age and sex matched, without MSy. Results. The median of plasmatic NT-proBNP level in MSy patients was 155 pmol/L significantly (p=0.002) higher than in the control group (120 pmol/L). Median NTproBNP was significantly higher (p=0.0266) in MSy patients presenting LVDD (160 pmol/L) as compared to those with normal left ventricular function (125 pmol/L).In the LVDD subgroup NT-proBNP level was positively and significantly correlated with age (r=0.326, p=0.025), SBP (r=0.508, p=0.0003) and DBP (r=0.396, p=0.005) and negatively correlated with waist circumference (r=-0.380, p=0.008). Dyslipidemia, impaired fasting glucose and body mass index (BMI) did not significantly influence NT-proBNP levels. Conclusions. MSy patients had higher NT-proBNP concentrations as compared to obese subjects without MSy, due to the presence of LVDD and the positive and statistically significant correlation with age, SBP and DBP.

Purpose. About 30% of patients with liver cirrhosis have diabetes. Postprandial hyperglycemia is more problematic than fasting hyperglycemia when managing diabetic patients with cirrhosis. Nateglinide decreases in the mealtime plasma glucose levels. The present study aims to determine\r\nwhether nateglinide is suitable for the management of diabetic patients with liver cirrhosis.\r\nMethods. This was a retrospective analysis of the cirrhotic patients who were treated at CNUH between Jan 2003 and Dec\r\n2009. A total of 81 Child-Pugh Class A or B patients who had been treated with insulin (I, n=27) or nateglinide (N, n=27) for at least 12 months were included in the study, while 27 cirrhotic patients without diabetes (C, n=27) were included as a control group. We compared the efficacy of treatment and the safety between the groups.\r\nResults. The basal mean HbA1c level was higher in the insulin treatment group than that in the nateglinide treatment group. The mean HbA1c was lowered in thepatients treated with insulin (9.36 ? 1.71% &#8594; 7.69?1.52%, p=0.026), but this was not changed in the patients treated with\r\nnateglinide (8.01?2.37 % &#8594; 7.78?2.11%, p=0.692) after 12 months treatment. There was no change in the Child-Pugh score in all the groups.\r\nConclusion. In case of mild hyperglycemia, nateglinide may be used for glycemic control in diabetic patients with\r\ncirrhosis as an insulin substitute without worsening the state of liver cirrhosis.

Denosumab,a monoclonal IgG2 antibody directed against RANK-L,is used as a neoadjuvant therapy for inoperable or metastatic giant cell tumor of bone. Many side effects like as hypocalcemia during treatment and rarely severe hypercalcemia especially in children after discontinuation of denosumab occurred. The unpredictable onset and recurrent episodes of severe hypercalcemia increase the duration of hospitalization and the risk of complications. Persistent hypercalcemia and difficulties in management have prompted the search for different more effective therapeutic options. Objectives. To share our experience with the use of oral bisphosphonate in acute and long-term therapy of severe hypercalcemia following high-dose denosumab therapy and to review the literature on this subject Case. We report the management of a case of severe hypercalcemia that developed 4 months after the completion of 18-month denosumab treatment in a 9-year-old girl who was followed up with a giant cell bone tumor for 6 years. Based on an evaluation aiming to determine etiology, hypercalcemia was considered as "rebound-linked" upon denosumab discontinuation. Severe hypercalcemia attacks recurring with an interval of 2 weeks were treated with IV bisphosphonate, but when mild hypercalcemia developed again, treatment with 70 mg per week of oral bisphosphonate was planned. After the second dose of alendronate, the calcium level always remained below 10.5 mg/dl. In the 14-month follow-up, no hypercalcemia attack was observed again. Results. Rebound hypercalcemia can occur as an unpredictable recurrent episode at any time after denosumab cessation. Thus, the patient should be closely monitored especially in childhood due to rapid bone cycle. In longterm follow-up, oral biphosphonates can be used effectively to reduce hospitalization time and the management of especially life-threatening recurrent attacks.

Introduction. The gold standard for surgery of fibroids is vaginal surgery and a preoperative treatment that facilitates this approach through reduction of the uterine\r\nvolume is of utmost importance. GnRH agonists and selective progesterone receptor modulators (SPRM) have both been tested to this effect.\r\nObjective. To evaluate whether uterine shrinkage induced by preoperative GnRH agonists in women with uteruses > 280g may\r\nfacilitate vaginal hysterectomy (VH).\r\nMaterial and methods. 23 women scheduled to have an abdominal hysterectomy based on the uterine size over 280 g were allocated to receive the GnRH agonist triptorelin 3.75 mg monthly for three months. Uterine weight (estimated by ultrasound), serum levels of estradiol and Hb were assessed before treatment and monthly afterwards three times.\r\nResults. Estradiol levels decreased from 235.9?15 to 38?3.7pg/mL at three months (p<0.0001), after an initial flare up. Hb increased from 11.85?1.8 to 12.7?0.74 g/dL.\r\nThe uterine weight decreased from 443.5?39 to 294.8?31 g (by 33.5%), all patients benefitting from a VH.\r\nConclusion. In women with a large uterus impending an abdominal hysterectomy, a 3-month preoperative course of GnRH agonists facilitates VH by decreasing uterine size by 30%.