ACTA ENDOCRINOLOGICA (BUC)

Background. The research evidence have suggested that ghrelin, a neuropeptide containing 28 amino acids, plays an\r\nimportant role in glucose homeostasis and its concentration is increased in diabetes.\r\nObjective. To investigate the relationship between the serum levels of ghrelin, insulin, fasting glucose and glycated hemoglobin in patients with type 2 diabetes mellitus.\r\nMaterials and Methods. Fasting glucose, insulin, ghrelin and glycated hemoglobin were measured after a 12-14 hours overnight fasting in 48 adult males with type 2 diabeties. Pearson correlations were used to establish the relationship\r\nbetween ghrelin concentration and other variables. P-value of less than 0.05 was considered statistically significant.\r\nResults. There were no correlations between serum ghrelin and Systolic and diastole blood pressure and body mass index (p<0.05). Serum ghrelin is weakly associated with glycated hemoglobin (p=0.076, R=0.19). Serum ghrelin concentrations were positively correlated with fasting glucose (p=0.005, R=0.40). In addition, ghrelin correlated negatively with\r\nserum insulin (p=0.013, r=-0.36).\r\nConclusion. Our data demonstrate that high ghrelin concentration is accompanied with increase in blood glucose\r\nin type 2 diabetic patients, and support this hypothesis that this neuropeptide plays a pathophysiological role in this disease.

Introduction: During the past thirty years bone biopsy has been used as an invasive diagnostic and research investigation of bone structure and metabolism. Quantitative bone histomorphometry parameters offer information on both bone mass and bone quality.\r\nObjectives: This study aimed to establish the value of routine qualitative bone biopsy evaluation in subjects with unexplained primary osteoporosis. Patients in whom low bone mineral density was not adequately explained by risk factors or patients in whom therapy\r\nwas not followed by BMD changes according to evidence-based data on treatment of osteoporosis were referred to bone biopsy. One-hundred seventy patients (73 men and 97 women), aged 54.29?0.95 years, were included in the study. The diagnosis was based on clinical data, lumbar spine and hip dual X-ray absorptiometry (DXA) evaluation and routine laboratory measurements. Bone biopsy was performed by horizontal approach, using an electric drill. Qualitative bone biopsy evaluation was performed in one single department by trained pathologists. Quantitative bone histology assessment (histomorphometry) was not available.\r\nResults: Of the 170 bone samples, secondary causes of low bone mineral density were identified in 19 patients (mastocytosis, multiple myeloma, myeloproliferative syndrome, sarcoidosis and osteomalacia). In 21 subjects with osteoporosis as defined by WHO criteria qualitative histological evaluation found no pathological changes. Accelerated bone resorption as expressed by the daily urinary levels of deoxypyridinoline (D-Pyr) and longterm sodium fluoride therapy were associated with relevant osteoidosis as assessed by qualitative evaluation of bone samples. Bone biopsy changes were not related to serum thyroid hormone, parathyroid hormone or 25-hydroxyvitamin D3 levels.\r\nConclusions: Qualitative bone biopsy evaluation may offer valuable information in the diagnosis of metabolic bone diseases in subjects with unexplained causes of low bone mineral density or in non-responders to anti-fracture agents. Despite of lack of quantitative information on bone mass and the degree of mineralization of bone tissue, few patients with osteoporosis may benefit from this diagnostic routine procedure.

Purpose. To correlate the volume of parathyroid adenomas with the hormonal and metabolic profile at patients diagnosed with primary hyperparathyroidism (pHPTH). Patients and Methods. Cross-sectional multicentric study, enrolling 52 patients with pHPTH from two medical institutions. Serum calcium and PTH were evaluated in all patients before surgery, whereas 25OHD3 was measured only in the 33 patients recruited form one medical unit. The volume of parathyroid adenoma was measured by using the formula of a rotating ellipsoid. Results. We observed a significant correlation of the volume of parathyroid adenomas with PTH at patients from the two units and in the whole group (p < 0.0001), but not with serum calcium (p = 0.494). Twenty-five out of the 33 patients at whom 25OHD3 was measured had levels in the range of deficiency. 25OHD3 was not correlated with PTH or calcium levels, but was negatively correlated to the adenoma volume and positively to the PTH/volume ratio (p = 0.041 and p = 0.048, respectively). Conclusions. The volume of parathyroid adenoma seems to be related to preoperative PTH and 25OHD3, but not to calcium level. Vitamin D deficiency is frequently found at patients with pHPTH and may contribute to particular disease profiles, including larger parathyroid adenomas.

Context. Changes in the secretion of signaling molecules that originates from adipose tissue and inflammation draw attention in the pathogenesis of type 2 DM. Chemerin, one of the signaling molecules of adipose origin, and irisin, defined as the Renaissance of the metabolism, are among these molecules. Objectives. This cross-sectional study was planned in order to compare the values of serum irisin and chemerin levels in patients newly diagnosed with T2DM and in healthy subjects. Subjects and Methods. The study included 41 patients newly diagnosed with T2DM and 49 healthy individuals. The chemistry parameters were analyzed with a biochemistry autoanalyzer, and hormonal parameters were analyzed with an immunoassay analyzer. Plasma irisin and chemerin levels were measured using the enzyme-linked immunosorbent assay method. Results. There was a significant difference between the groups in terms of glucose, HbA1C, Insulin, HOMA-IR and lipid panel results. Irisin levels in the group of patients newly diagnosed with T2DM were lower than in the control group. Chemerin levels in the group of patients newly diagnosed with T2DM were higher than in the control group. Conclusion. Consequently, diabetes-dependent changes in chemerin and irisin concentrations suggest that these two hormones have a role in the pathophysiology of DM. Further studies are required to understand the complex structure of the signaling pathways of chemerin and irisin molecules as well as the physiological importance of these molecules as metabolism regulators especially in humans.

Context. Both human immunodeficiency virus (HIV) infection and hepatitis C virus (HCV) infection represent systemic diseases that may develop metabolic complications, thus HIV/HCV coinfection metabolic changes need to be depicted. Objective. We aimed to evaluate the body composition changes in patients with either HIV and HCV monoinfections or HIV/HCV coinfection. Methods. 123 young men divided into three groups: 41 with HIV/HCV coinfection, 42 with HIV-monoinfection, and 40 with HCV-monoinfection were evaluated for total and regional bone and soft tissue body composition assessments using a Dual-energy X-ray absorptiometry (DXA) and were compared with 40 healthy men with age and body mass index similar to the study groups. To detect sarcopenia, we calculated the appendicular limbs’ lean mass index (ALMI), for obesity, we used the percent of body fat, and for lipodystrophy, we calculated the trunk/limbs index. Results. HIV/HCV coinfection is associated with a significant higher bone demineralization in all regions of interest compared to HCV or HIV monoinfections and to controls. The prevalence of bone demineralization in HIV/ HCV patients was 31.7%, more frequently at lumbar spine. Fat mass and lean mass were significantly lower in HIV/ HCV-coinfected patients than in controls. Lipodystrophy was found in similar percentages in all three evaluated groups (80.4% in HIV/HCV, 92.5% in HIV, and 95% in the HCV group). Sarcopenia was higher in HIV/HCV group (43.9%) and important in HCV-monoinfection group (30%). Conclusions. HIV/HCV-coinfected patients had the highest prevalence of bone demineralization, fat mass, and lean mass loss, compared to controls and to HIV and HCV monoinfections.

Background. Insulin degludec/aspart (IDegAsp) is a co-formulation with IDeg and IAsp. Different insulin regimens may be switched to IDegAsp. In this study, we aimed to find out the effect of switch to IDegAsp on glycemic control and whether the basal characteristics and treatment modalities of the patients affect the change in glycemic control brought by switch to IDegAsp. Methods. We retrospectively analyzed the records of 78 patients whose insulin therapies (basal+bolus, premixed analogues or basal only) were switched on a 1:1 unit basis to IDegAsp±bolus insulin. Oral antidiabetic agents (OADs) given were recorded. At the end of 12th and 24th week, total insulin doses of patients and HbA1c were compared to the baseline. Results. There was a statistically significant decrease at HbA1c at 12 weeks (1.4%; p<0.001). There was not a significant difference in HbA1c between the OAD added group and the group with no new OADs(p=0.1). Basal insulin dose was not statistically different from baseline, whereas bolus insulin dose was significantly lower (p=0.007). At the end of 24 weeks the decrease in HbA1c level from baseline was preserved. Conclusion. Regardless of the baseline insulin regimen, diabetes type and oral antidiabetic drugs given, HbA1c is significantly lowered after switching to IDegAsp.

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.

Context. Data are conflicting concerning risk for Alzheimer’s disease (AD) and 5,10-methylenetetrahydrofolate reductase genetic variant (MTHFR C677T). Objective. The aim of the study was to investigate the associations of MTHFR C677T and risk of developing AD. Design and Methods. We searched the relevant articles by using Medline, web of science, and abstracts of conference proceedings. The meta-analysis and statistical analyses were performed using Stata. Results. In 33 included studies which provided 4518 cases and 5476 controls, the analysis for investigating the association between C677T allele T and the risk of developing AD relative to the allele C revealed no heterogeneity (p=0.088, I2=26.1%) between the 33 studies; the random effects (RE) pooled OR was significant: [RE OR=1.13(1.05-1.22)]. In subgroup analysis, we only observed the significant results in Asian populations. The pooled analysis for MTHFR 677 CT+TT vs. 677CC revealed a significant result [fixed effect (FE) OR=1.22(1.10-1.34)]. However, we did not observe significant associations in Europeans when comparing MTHFR 677 CT+TT with 677CC in subgroup analysis. The pooled analysis for MTHFR 677 TT vs. 677CC+CT did not reveal significant results: [FE OR=1.08(0.95-1.22)]. Conclusion. The risk allele T of MTHFR C677T is associated with high risk of AD in Asian populations, but not in Europeans.

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.

Background/Aims. Growth hormone (GH) treatment has severe cost burden on patients, their families, and healthcare systems. Therefore, accuracy of diagnosis should be confirmed; factors affecting the response to treatment should be defined. The present study is performed to evaluate auxiliary diagnostic parameters and factors affecting treatment in growth hormone deficiency (GHD). Methods. In this study, 142 patients under the age of 16, with at least one year of treatment, were included. Treatment dose of somatropin was 0.2 mg/kg/week in all cases. Response to treatment was evaluated by measuring annual height and height standard deviation score (SDS) gains every 3 months. Results. Male to female ratio was 79 to 63, and follow-up duration before the treatment was 0.89±0.38 years. Annual growth rate before the treatment was 2.92±1.02 cm, and age at the treatment initiation was 9.97±3.22 years. Height gain SDS at the end of the first year was significantly higher in cases which were at the prepuberty, had severe short stature, low height SDS-mid parental height SDS (HSDS-MPHSDS), and initiated treatment at earlier ages. Correlations in height gain and height SDS gain at the end of the first year were significant between bone age at treatment baseline, delta SDS factors, L-dopa and clonidine stimulation results (both are p<0.01). Conclusion. Height gain was positively related to body mass index, whereas negatively to bone age at treatment baseline, responses obtained from stimulation tests, and delta SDS values. In the treatment evaluation, the parameters which can affect according to model chosen by the investigator, may differ.