ACTA ENDOCRINOLOGICA (BUC)

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% → 7.69?1.52%, p=0.026), but this was not changed in the patients treated with\r\nnateglinide (8.01?2.37 % → 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%.

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.

Aim. To investigate the cause of infertility in an azoospermic man and to describe the phenotype of a new 46,XX male case. Case report. We present the case of an infertile man, 33 years old, with a history of several years of infertility, diagnosed with the 46,XX male syndrome, SRY positive. The patient was diagnosed by clinical, hormonal, ultrasound and genetic criteria. Our patient was born at 39 weeks of pregnancy, from unrelated parents. The mother’s age was 22 years old and father’s age was 23 years old at the time of the conception. Both of his parents were exposed to chemical noxae before his conception. The case we report is a SRY positive 46,XX male with complete masculinization, confirmed by FISH and molecular analyses, caused by an X/Y chromosome inter-change during paternal meiosis. Conclusions. In our case, the SRY translocation, could probably be related to the paternal exposure to external factors like chemical noxae, but more data are necessary. Cytogenetic and molecular analyses are necessary for an accurate diagnosis, as well as endocrine testing and pelvis ultrasound.

Epidemic of obesity is ongoing and did not slow down. Causes of obesity are numerous and very complex. Among them, the concept of bidirectional signaling within the brain-gut-microbiome axis was recently proposed as possible pathophysiological mechanism and become a hot topic in the explanations for the control of food intake. Discoveries of new anti-obesity drugs that are analogs for the receptors for some hormones derived from gastrointestinal tract contribute to the investigations in this area. The human gut microbiota plays a fundamental role in human health and disease and it is considered that it represent an endocrine organ that participate in energy homeostasis and host immunity. Role of gut microbiome has been investigated in metabolic diseases such as obesity, type 2 diabetes and non-alcoholic fatty liver disease. Gut microbiome participate in regulation of various mechanisms inside the gastrointestinal tract due to its production of different bacterial metabolites. In our manuscript we present current knowledge about microbiota in the gut; the relation between gut microbiota and brain; neuroendocrine system and gut-brain axis; immune system and gut-brain axis; endocrine system and gut-brain axis; the role of gut microbiota in obesity development and possible use of gut microbiota for the treatment of obesity.