ACTA ENDOCRINOLOGICA (BUC)

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. 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.

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%.

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.

Hypoglycemia from a non-insulin-secreting extrapancreatic tumor is a paraneoplastic syndrome characterized by the tumor production of a substance with an insulin-like effect (insulin-like growth factor 1 or 2 - IGF 1 or 2). Diagnosis is confirmed by the determination of IGF-1 and IGF-2 and finding an elevated IGF - 2/IGF- 1 ratio. The availability of these tests is limited in many laboratories, so prompt recognition and therapies are late. We present the case of a 70-year-old patient diagnosed with right lower lobe bronchopulmonary neoplasm who presented to the emergency department with an altered general condition and hypoglycemic coma. The evaluation revealed low levels of insulin and C-peptide along with an elevated IGF-2/IGF-1 ratio of more than 10, suggesting a diagnosis of lung sarcoma with production of IGF-2. Because the tumor could not be resected in this case, chemotherapy and radiotherapy were performed, along with glucocorticoid therapy to prevent recurrent hypoglycemia. In the case of a patient with lung sarcoma and recurrent hypoglycemia (especially severe hypoglycemia or coma), extrapancreatic non-hyperinsulinemic hypoglycemia should be determinate tumor IGF-2 secretion.

Based on epidemiological, clinic, biochemical and hormonal data (both personal and\r\ninternational), our personal view is that natural history of autoimmune type 1 diabetes could\r\ninclude the following stages: 1) The presence of a complex genetic predisposition towards ?\r\ncell autoimmunity (possibly &#8220;latent&#8221; until death); 2) The &#8220;initiation&#8221; of autoimmunity in\r\nsubjects carrying a defect in the post-translational processing of pre-proinsulin/ proinsulin/\r\ninsulin, manifested precociously as increased proinsulin-to-insulin ratio; 3) Stimulation by the\r\nincreased proinsulin of the plasmacytoid dendritic cell clones capable to capture the natural\r\nantigens (proinsulin/insulin, Glutamic Acid Decarboxylase, etc.) from the pancreatic beta\r\ncells; 4) Activation of the process generating reactive T cell clones (Teffs) in the detriment of\r\nprotective immuno-regulatory T cell clones (Tregs), triggering the anti-beta cell attack,\r\nexpressed as autoimmune insulitis and/or the presence of circulating anti beta cell antibodies;\r\n5) The onset of the beta cell apoptosis process mediated by pro-inflammatory cytokines (IFN\r\n?, TNF ?, IL6) or by the direct contact between Teffs and the beta cells; 6) Identification of\r\nthe first secretory beta cell defects (the loss of the first phase insulin response followed by the\r\nprogressive decrease of the area under the insulin curve and the progressive increase of the\r\narea under the blood glucose curve) while fasting glycemia is still normal; 7) The progressive\r\nloss of the beta cell mass. All these processes take place during the pre-hyperglycemic stage\r\nof diabetes, with a higher or lower speed depending on the genetic background. The overt\r\nclinical stage of diabetes, marked by the presence of hyperglycemia, occurs rather late, when\r\nmore than 90% of the beta cell function/mass is irreversibly lost.