ACTA ENDOCRINOLOGICA (BUC)

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.

Objective. This study has two objectives. The first was to determine the cancer incidence in MNG cases, and to compare this with the thyroid cancer incidence in endemic goiter regions in our country and the rest of the world. The second objective was to evaluate the relationship between the dominant nodule diameter and the cancer incidence. Method. One hundred seventy-six patients who had presented to the Erzurum Oltu State Hospital General Surgery Clinic between October 2009 and March 2012 with the diagnosis of MNG, and who had undergone total thyroidectomy, were evaluated retrospectively. Findings. Papillary carcinoma was determined in 14 (8%) cases; medullary, anaplastic and follicular carcinoma were determined in 1 case each (0.6%). In 31 patients, the dominant nodule diameter was > 4cm, and malignancy was determined in 7 (22.6%) of them. Conclusion. The increase in the malignancy incidence was statistically significant in cases in which the dominant nodule diameter was > 4 cm. However, the frequency of thyroid papillary carcinoma was determined as 12.9% in MNG patients in whom the DND was > 4 cm.

Objective. Infertility affects an estimated 17.5% of couples worldwide, according to the last report published in 2023 by WHO. A significant cause of this global fertility decline is due to environmental endocrine-disrupting chemicals exposure, which have the ability to interfere with the endocrine system. Bisphenol A (BPA), a synthetic chemical product leads to health concerns for its endocrinedisrupting properties. Jujube honey contains antioxidants and active compounds, has various therapeutic properties. This study aims to determine testicular dysfunction and endocrine imbalance induced by BPA chronic exposure and the possible protective effect of jujube honey in gerbil. Materials and methods. Eighteen adult male gerbil was either considered as control (n=6, group 1) or exposed to 50 mg BPA/kg/day Group 2, n=6) and the BPAtreated group was given jujube honey at 200 mg/kg/day by oral gavage Group 3, n=6) for six weeks. At the end of the experiment, testicular weight, epididymal sperm count, endocrine status, histopathology of testis tissue and oxidative stress parameters were evaluated. Results. The results showed a decrease in testicular weight, sperm quality and plasma levels of testosterone and estradiol in the BPA-treated group. Furthermore, histopathological findings revealed germinal epithelium alteration characterized by germ cell degeneration, disordered arrangement of the germ cell layers and vacuolization and decreased number of Ki-67-positive germ cells. The results showed a decrease in testicular levels of superoxide dismutase, catalase and reduced glutathione with an increase of malondialdehyde in the BPA-treated group. However, in the jujube honey+BPA group, histopathological studies revealed a systematic array of germ cells with less vacuolization, improved sperm parameters, restored plasma testosterone and estradiol levels and increased antioxidative capacity of the testes. Conclusion. These findings suggest a potential protective effect of jujube honey against BPA-induced testicular damage and oxidative stress caused by endocrinedisrupting chemicals.

Context. Results concerning the relationship between the risk of developing diabetic retinopathy (DR) and methylenetetrahydrofolate reductase genetic variant (MTHFR C677T) are inconclusive. Objective. The aim of the present analysis was to investigate the associations of DR with MTHFR C677T. Design and Methods. We searched the relevant articles by using Medline, web of science, and abstracts of conference proceedings. The meta-analysis was performed using Stata. Results. The included 7 studies provided 535 cases of DR and 759 controls. The main analysis for investigating the association between MTHFR 677 TT and the risk of developing DR relative to the 677 CC did not reveal significant heterogeneity (p=0.227, I2=27.6%) between the studies; the fixed effects (FE) pooled OR was significant: FE OR=1.84(1.30-2.61). The analysis for the association between MTHFR 677 TT and the risk of developing DR relative to the 677 CC+CT revealed heterogeneity (p=0.082, I2=48.9%) between the studies; the random effects (RE) pooled OR was significant: RE OR=1.72(1.07-2.76). In addition, T carriers have 31% higher risk of developing DR compared with homozygotes for C [OR=1.31(1.03-1.66)]. Conclusions. The present metaanalysis suggested an association between MTHFR C677T and DR and provided evidence that the TT genotype of the MTHFR C677T contributes to susceptibility to DR.

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.

Detecting the primary tumours in carcinoid malignancies is a critical challenge. We report the case of a 25 year old male patient with a typical clinical carcinoid syndrome. Metastatic carcinoid malignancy was easily diagnosed by very high plasma chromogranin, plasma serotonin and urinary 5-Hydroxy-Indol Acetic Acid levels, and the detection of multiple liver metastases by ultrasound. Somatostatin receptor scintigraphy (SRS) failed to detect the primary lesion, as did upper and lower gastrointestinal (GI) tract endoscopy, bronchoscopy, total body CT, MRI, and GI video tract endoscopy; only F-DOPA PET-scan ascertained and accurately localized the primary ileal tumor. Surgery confirmed the localisation, and pathology revealed a 3 cm highly differentiated carcinoid tumor with low proliferation grade (Ki67<2). The therapy with short and long acting somatostatin analogues was started before surgery and continued after surgical intervention. There was a regression of the clinical carcinoid syndrome and a numerical involution of liver metastases, but the levels of chromogranin A and serotonin remained elevated. Other therapeutical option should be discussed.

Context. In HIV+ patients, several factors related to patient and antiretroviral therapy (ART) could determine early onset of bone mineral density (BMD) disturbances. Objective. Evaluation of bone quality according to gender in patients from the HIV Romanian cohort. Design. A cross-sectional study in “Prof. Dr. Matei Balș” National Institute for Infectious Diseases, Bucharest between 2016-2018. Subject and Methods. We collected data regarding HIV infection, ART history, viral hepatitis co-infections and we calculated patients body mass index (BMI). CD4 cell count, HIV viral load (VL), vitamin-D levels were determined. Dual-energy X-ray absorptiometry (DXA) scans were used to evaluate BMD. Results. We enrolled 97 patients with the median age of 26 years. According to the DXA T-scores, 10 males and 8 females had osteopenia and 4 males and 4 females had osteoporosis. According to Z-scores 2 males and 1 female had osteoporosis. Hip DXA T-scores revealed osteopenia in 6 males and 9 females, whereas T and Z-scores showed osteoporosis in 2 males and 3 females. Lumbar spine (LS) T-score diagnosed osteopenia in 9 males and 6 females, while T and Z-scores revealed osteoporosis in 3 males and females. In males, low T-scores were associated with decreased BMI; low LS DXA Z-scores with low vitamin-D levels; low T and Z-scores and LS-BMD with high VL. Conclusions. Evaluating bone quality in patients with a long history of HIV infection, multiple factors should be taken into account.

Context and objective. Reactive oxygen species (ROS) produced under oxidative stress is important for osteoclastogenesis. As a major member of the metallothionein (MT) family, metallothionein2 (MT2) can scavenge ROS in osteoblasts. However, the role of MT2 in osteoclastogenesis and ROS production in osteoclast precursors (OCPs) is unknown. Material and methods. In this study, we first investigated MT2 expression level in osteoporotic model mice. Next, we explored the roles of MT2 in osteoclastic differentiation and ROS production in OCPs. Ultimately, via rescue assays based on hydrogen peroxide (H2O2), the significance of ROS in MT-2-regulated osteoclastic differentiation was further elucidated. Results. Compared with sham operated (Sham) mice, ovariectomized (OVX) mice displayed bone marrow primary OCPs (Ly6C+CD11b-) having higher ROS levels and lower MT2 expression. MT2 overexpression inhibited the formation of mature osteoclasts, while MT2 knockdown was contrary. Moreover, MT2 overexpression inhibited ROS production in OCPs, while MT2 knockdown exhibited the opposite effects. Notably, the inhibitory effect of MT2 overexpression on osteoclastogenesis and ROS production was blocked by the addition of H2O2. Conclusion. MT2 inhibits osteoclastogenesis through repressing ROS production in OCPs, which indicates that the strategy of upregulating MT2 in OCPs may be applied to the clinical treatment of osteoclastic bone loss.

Objective. To evaluate the effect of multiple daily injection (MDI) treatment replaced by Exenatide BID as compared with continuation of MDI. Patients and Methods. A total of 140 patients with type 2 diabetes, taking metformin and multiple daily insulin injections, were randomized to exenatide or insulin group that continued their insulin treatment. Patients were followed-up for 16 weeks. Blood glucose profiles, BMI, waist circumference, HbA1C, serum lipids and side effects were assesssed at weeks 0,12 and 16. Results. There were no significant differences between the two groups with respect to baseline parameters. Glycemic control was similar between the two groups. The mean changes in HbA1C in exenatide group were -0.66±0.63% and in insulin group -0.74±0.92 % (p=0.594). In exenatide group, 59.6 % of patients and in insulin group 85.71 % of patients had maintained or improved glycemic control at the end of the study. In insulin group, insulin requirement increased 5.86 ± 4.46 units/day. Body weight and waist circumference decreased significantly in exenatide treatment group with respect to insulin group (p<0.001). Conclusions. Substituting exenatide for insulin might be an option in insulin-treated, type 2 diabetic patients having obesity, and poor glycemic control. However, patients with longer duration of diabetes and insulin treatment and with lower C-peptide levels might not benefit from exenatide therapy.