ACTA ENDOCRINOLOGICA (BUC)

Introduction. Vitamin D (VD) levels were correlated with different health conditions, including reproductive disorders in males. Vitamin D action is mediated through vitamin D receptor (VDR), which acts as a transcription factor. VDR gene promoter is embedded in a GC-rich island. The VDR gene has been shown to have several polymorphisms that affect the receptor function. Aim. To examine the relationship between Cdx- 2 polymorphism (rs17883968), the methylation status of VDR’s promoter and serum levels of 25-hydroxyvitamin D in male infertility. Patients and Methods. A total of 69 infertile men and 37 age-matched controls were enrolled in this study. Vitamin D level assessments were detected using the electrochemiluminescent method. Cdx-2 VDR polymorphism identification was performed by PCR on DNA samples from blood, followed by restriction. Methylation of VDR gene promoter was assessed by qMS-PCR using bisulfite-treated DNA from fresh sperm. Results. Vitamin D levels was found to be significantly decreased in infertile groups compared the controls (p=0.0279). The GG genotype was found in a higher percentage in controls and the AA genotype was higher in infertile group (p=0.0056). Infertile homozygote (GG) and heterozygote (GA) individuals had significantly higher vitamin D levels than AA homozygote. Methylation is higher in individuals with lower vitamin D levels and AA genotype is characterized by higher methylation values. Conclusion. The results provide new insights of Cdx-2 polymorphism is involved in vitamin D deficiency, highlighting the important role of epigenetic modification of vitamin D receptor and male infertility along with the genetic context.

The prerequisite for developing methods for type 1 diabetes mellitus prevention is to know its pathogenic mechanisms. The aim of this work was to characterize a group of children with type 1 diabetes mellitus regarding pancreatic antibody positivity and fasting C peptide concentrations. The study group enrolled 117 children, 61 boys (52.1%), mean age 12.7?3.1 years. Islet cell antibodies, glutamic acid decarboxylase antibodies (GADA), IA-2 antibodies (IA-2A) and fasting C peptide were measured. Sensitivity for GADA and IA-2A tests was 85% and 75%, respectively. Specificity for the tests was 87.1% and 98%, respectively. The threshold for pancreatic antibody positivity was considered the 97.5th percentile, and normal values for fasting C peptide were between the 5th and 95th percentiles from a control group (n=73), matched for age and gender. Thirty-nine patients (33.3%) were positive for 1 antibody, 10 (8.6%) were positive for 2 and 2 (1.7%) were positive for all 3 antibodies. The positivity for pancreatic antibodies and for islet cell antibodies was significantly lower in patients with diabetes duration>2 years, compared with the rest: 32% vs. 52.2% (p=0.03) and 6% vs. 20.9% (p=0.03), respectively. Mean fasting C peptide and the percentage of patients with normal C peptide decreased significantly one year after the diagnosis of diabetes: 0.20?0.40 ng/ml vs. 0.44?0.57 ng/ml (p=0.03) and 9.5% vs. 27.3% (p=0.02), respectively. In conclusion, in children with type 1 diabetes mellitus, pancreatic autoimmunity is more intense in the first two years of the disease and insulin secretion decreases one year after the diagnosis.

Context. Nonalcoholic fatty liver disease is common in type 2 diabetes mellitus patients, being difficult to diagnose. Objective. To find a correlation between elastographic parameters and lab results, for facilitating the diagnosis of nonalcoholic fatty liver disease. Design. This is a cross sectional study, conducted at the Departments of Diabetes, Nutrition and Metabolic Diseases, and Gastroenterology and Hepatology, of the Clinical Emergency Hospital “Pius Brinzeu” Timisoara. Subjects and Methods. We included 190 type 2 diabetes mellitus patients, collected data regarding medical history, clinical and biological features and applied the Alcohol Use Disorders Identification Test. We excluded patients with other causes of liver disease. Liver steatosis and fibrosis were evaluated through transient elastography, yielding two parameters: liver stiffness as an indicator of liver fibrosis stage, expressed in kPa, and liver steatosis stage, assessed by controlled attenuation parameter, expressed in dB/m. Data were analyzed using SPSS 15. Results. The analyzed group comprised 113 patients. Elastographic measurements showed that 93.8% of the patients had steatosis (controlled attenuation parameter ≥232.5 dB/m) and 70.8% severe steatosis (controlled attenuation parameter ≥290 dB/m). Severe steatosis was more common in women (75.7%) than in men (68.1%) (p<0.0001). From the patients with steatosis, 47.2% had liver stiffness values suggestive for fibrosis and 19.8% for cirrhosis. Most patients with steatosis and severe fibrosis were obese (66.7%). Triglycerides/HDLc ratio >4 correlated with hepatic steatosis (p=0.04), being more common in patients with severe fibrosis/cirrhosis (58.3%) than in those with absent or mild fibrosis (36.2%). Conclusions. Our study found a clear correlation between type 2 diabetes mellitus and the presence of liver steatosis. It correlates with body mass index, waist circumference (in men) and triglycerides/HDLc ratio. Controlled attenuation parameter is a useful noninvasive method for detection and quantification of liver steatosis.

The detection of thyroid nodules in a patient with Graves&#8217; disease is not a rare event.\r\nThe management of these cases still represents a controversial problem for clinical practice.\r\nThis paper describes the case of a patient with Graves&#8217; disease and a concurrent\r\nfollicular thyroid carcinoma, presenting as a clinical palpable nodule in the right lobe.\r\nThyroid function tests confirmed thyrotoxicosis. Immunological investigations showed high\r\nlevels of TSH-R antibodies. Thyroid ultrasound revealed an increased thyroid volume with\r\na diffuse low echogenicity of parenchyma and in the right lobe a single homogeneous\r\nhypoechoic nodule. The scintiscan indicated the presence of a &#8220;cold nodule&#8221; in the right lobe\r\nand increased uptake in the rest of parenchyma. Antithyroid drug therapy was\r\nrecommended. Cytological exam indicated an &#8220;indeterminate&#8221; smear. After euthyroidism\r\nwas achieved, surgical therapy was recommended and near total thyroidectomy was\r\nperformed. The morphopathological exam revealed an invasive follicular carcinoma on a\r\ndiffuse thyroid hyperplasia (Graves&#8217; disease). This case report is followed by a discussion\r\nabout the incidence of malignancy in thyroid nodules concurrent with Graves&#8217; disease. The\r\ncriteria that raised concern about a possible malignancy of the nodule are presented.\r\nIn conclusion, we recommend that patients with Graves&#8217; disease should undergo a\r\nregular examination of the thyroid gland for an early detection of possible malignant\r\nnodules. The intervention of choice in these cases should be near total or total\r\nthyroidectomy, if malignancy cannot be excluded by preoperative evaluation.

Introduction. Ties between the endocrine system and mental health are undeniably a consistent point of interest in modern day medicine. Furthermore, mental disturbances due to hormonal changes following childbirth have been mentioned in medical literature since Hippocrates. Considering the dramatic endocrine, paracrine and autocrine changes that occur during gestation, labour and postnatal phase, hormonal theories are not to be ignored in the treatment of postpartum disorders. Results. Reproductive hormones are known to modulate behavioural, emotional and cognitive response, therefore rapid changes in estradiol and progesterone plasma concentrations during pregnancy and labour create a vulnerable terrain leading towards postpartum disorders. New research shows that women suffering from postpartum disorders have abnormal neural responses, suggesting a neuroendocrine explanation for postpartum syndromes. Conclusion. To facilitate further research in this area, we present new information on several hormonal interactions and the psychiatric response involved in pregnancy and labour, offering an interdisciplinary outlook on pregnancy and postpartum disorders. There is enough evidence to suggest that estradiol, progesterone, oxytocin, cortisol and thyroid hormones are some of many hormones involved in postpartum syndromes and tackling their perinatal imbalance with pharmacological substituents or antagonists could be useful as an adjuvant form of treatment in future patients.

Introduction. Pulmonary hypertension (PHT) is a quite frequent echocardiographic finding in hyperthyroid patients and it regresses slowly under therapy with thiamazol.\r\nAim. The aim of the study was to follow the evolution of PHT over a period of a year, in two groups of hyperthyroid patients.\r\nMaterial and Methods. We followed up two groups of patients: one consisted of patients with chronic Graves Basedow\r\ndisease, some of them with good response to antithyroidian treatment and some other patients with repeated episodes of\r\ndecompensation despite medical therapy. The second group contained new diagnosed cases, a supgroup of patients with overt hyperthyroidism and one with subclinical forms. All 4 subgroups were followed over a period of 12 months. These subjects underwent thyroid hormone determinations and echocardiographic examination at 0, 1, 3, 6 and 12 months.\r\nResults. Our study group consisted of 92 patients with hyperthyroidism of different etiologies. None of the subjects had pulmonary or cardiovascular diseases severe\r\nenough to cause PHT by itself. We determined the presence and severity of pulmonary hypertension at the initial visit and followed its evolution at each scheduled visit in all four subgroups. All patients got antithyroidian therapy with thiamazol, but some chronic cases, with episodes of exacerbation, needed adjustments of their initial treatment. We noticed that PHT appeared in a higher percent and was more severe in the patients with severe hyperthyroidism or in the chronic cases with poor therapeutic response. We observed after some months a tendency to regression in\r\nthe well controlled patients or in those with subclinical disease.\r\nConclusion. The duration and severity of hyperthyroidism had a strong influence on the evolution of pulmonary hypertension in our patients.

Our aim was to explore the interactions of intercellular adhesion molecule (sICAM-1), TNF-&#945; (tumor necrosis factor-&#945;), interleukin-1&#945; (IL-1&#945;) and interleukin-6 (IL-6) with\r\ndopamine agonists in a culture of adenomatous cells from an nonfunctional macroadenoma.\r\nMaterials and methods. Tissue specimen from pituitary macroadenoma removed in transsphenoidal surgery was prepared for primary culture. Cells were counted and plated at 105/well into 24-well plates in a final volume of 1ml. Cabergoline in molar doses of 10-6, 10-7, 10-8, 10-9 was added and the cells were incubated for 4 days. sICAM-1, TNF-&#945;, IL-1&#945;, IL-6 were measured from cell-culture supernatants by ELISA kits.\r\nResults. sICAM-1, TNF-&#945;, IL-1&#945; and IL-6 were detected in the untreated control cultures after a 4d period. There was a negative correlation between TNF&#945; and IL-1&#945; (p=0.007).\r\nThe levels of PRL and hGH had measurable values above those found in culture medium without tumor cells. PRL positively correlated with IL-1&#945; ( p=0.05). hGH positively correlated with cell proliferation (p=0.049). Cabergoline treatment showed that IL-6 progressively decreased with the dose, ranging from -27.41% to -76.44%. TNF-&#945; significantly decreased (-65.90%; p<0.03)at the cabergoline 10-7 M dose. IL-1&#945; progressively increased with cabergoline dose, ranging\r\nfrom -2.53% to 345 %. sICAM-1 was significantly reduced by cabergoline at 10-9 (-47.12 %; p=0.045) and 10-6 M (-59.16%; p=0.01) doses. TNF-&#945; positively correlated with PRL (p=0.025); IL-6 positively correlated with hGH (p=0.044); sICAM-1 negatively correlated with hGH\r\n(p=0.009), TNF&#945; (p=0.025) and IL-1&#945; (p=0.044).\r\nConclusions. These data support the existence of an immunoendocrine network in pituitary tumorigenesis; TNF-&#945;, IL-6, IL-1&#945;, sICAM-1 significantly interfered by cabergoline\r\ntreatment in a dose-dependent way. However, future studies on different types of pituitary tumours are needed to confirm these findings.

Background. Genetic variants of the endothelial nitric oxide synthase (eNOS) gene have\r\nbeen reported to be associated with cardiovascular disease. We hypothesized that G894T\r\npolymorphism might trigger many of the endocrine-metabolic changes related to metabolic\r\nsyndrome (MetS).\r\nStudy Design. 148 subjects with MetS and 142 healthy control subjects aged 23-60 years\r\nwere studied. Fasting serum levels of insulin, cortisol, 17-OH Progesterone, DHEA,\r\nandrostendione, IGF1, GH, PRL, CRP, resistin and biochemical profile were evaluated. G894T\r\n(eNOS) polymorphism was assayed by using PCR-RFLP technique.\r\nResults. The frequencies of genotypes and alleles of G894T polymorphism did not deviate\r\nfrom the Hardy-Weinberg equilibrium. In the MetS group the percentages of both GT (51.35 vs.\r\n39.44; OR=2.09; CI=1.27-3.45; p= 0.003) and TT (16.22 vs. 8.45; OR=3.08; CI=1.41-6.74;\r\np=0.003) genotypes and T allele (41.9 vs. 28.2; OR=1.83; CI=1.3- 2.6; p=0.0005) significantly\r\nincreased compared to control group. The G894T polymorphism was more significantly\r\nassociated with the MetS in the presence of cortisol, 17-OH Progesterone, PRL, IGF1 and CRP\r\n(OR= 8.20; 95%CI=2.31-29.08; p=0.001) and significantly stronger in the presence of IGF1,\r\nPRL, 17OHP, resistin and CRP (OR= 10.21; 95%CI=2.42-43.05; p=0.002). The T allele carriers\r\nhad higher values of waist circumference, systolic and diastolic blood pressure, cortisol, 17-OHP,\r\nandrostendione, PRL, resistin and lower values of glucose, HOMA-IR in MetS group; The TT\r\ngenotype carriers had higher values of triglyceride in both control and MetS group.\r\nConclusion. Our results show an interaction between the G894T polymorphism and its\r\nphenotypes in conferring a higher susceptibility to the endocrine changes involved in\r\npathogenesis of MetS suggesting a role of the eNOS gene in the modulation of the molecular\r\nendocrine mechanisms.

Background. We describe a case of denosumab-related osteonecrosis of the jaw in a 58-year-old patient with a diagnosis of osteoporosis, treated with Denosumab and a short-time course of bisphosphonates. This case illustrates that use of anti-RANKL agents can lead to a type of osteonecrosis resembling bisphosphonate-related osteonecrosis of the jaws, so this medical condition can be categorized as of antiresorptive - induced osteonecrosis of the jaw. The consensus of present day medical opinion is that the benefits of antiresorptive therapy outweigh the disadvantages. However, to provide optimal management for individual patients, the risk-benefit ratio of osteoporosis therapy must be repeatedly assessed at all stages of a patient’s treatment, and therapeutic decisions taken in the light of the ratio as it applies to the individual.

Introduction. The published data showed the importance of metabolic control in preventing complications in metabolic syndrome (MS) and the role of nutritional medical therapy in glycemic control and in the control of dyslipidemia, hypertension, weight loss/normalization (in overweight or malnourished subjects). Objectives. This study follows the evolution of sarcopenic index (SI) and other clinical parameters (body mass index (BMI), homeostasis evaluation index (HOMA index)) correlated with MS after diet therapy or diet therapy combined with sports, in patients with MS. Patients and methods. Our research was conducted during 12 months, on 110 patients >18 years of age, with HOMA index>2, divided into three groups: control group (CG, N=20), diet therapy group (DTG, N=58), diet therapy and sports group (DTSG, N=32). HOMA index for insulin resistance was calculated as the product of resting plasma insulin (in microunits/milliliter) and plasma glucose (in millimoles/liter), divided by 22.5. SI was determined using BIA, as being the ratio between muscle mass and fat mass, measured in cm2 /m2 . Results. A significant decrease of BMI (p<0.05) in DTG (from 31.63 to 24.50) and DTSG (from 30.18 to 24.17) vs. CG was observed (Pearson coefficient r=0.281, p<0.001). Weight status changed significantly (p<0.05) in the high-risk patients. There was a significant decrease of HOMA index (p<0.05) in DTG (from 5.93 to 2.57), DTSG (from 3.93 to 2.23), and in CG an increase was observed (from 3.15 to 3.37). Conclusion. The best results in the prevention/ treatment of sarcopenia in MS patients were obtained for DTSG, which benefited from both the positive effect of diet and physical activity.