ACTA ENDOCRINOLOGICA (BUC)

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Context. Regulatory T cells (Tregs) have critical roles in preventing autoimmune diseases such as Hashimoto’s thyroiditis (HT). Forkhead box P3 (Foxp3), the master transcription factor of Tregs, plays a pivotal role in Treg function. Objective. Herein, we investigated the association of two single nucleotide polymorphisms (SNPs) of the Foxp3 gene with HT development. Methods and study design. A total of 129 HT patients and 127 healthy subjects were genotyped for rs3761548 (-3279 A/C) and rs3761549 (-2383 C/T) in the Foxp3 gene, using polymerase chain reaction-restriction fragment length polymorphism. Results. Genotypic and allelic distribution of rs3761548 SNP showed a significant association with HT. The CC genotype was observed in 37.2% of patients versus 22.1% of the controls [P<0.008, odds ratio (OR): 2.1; 95% confidence interval (CI): 1.2-3.6] and the AC genotype in 41.1% of patients compared to 54.3% of the controls (P<0.025, OR: 2.1; CI: 1.2-3.6). In addition, higher frequency of C allele in patients compared to controls (P=0.05, OR: 1.4; 95% CI: 0.9-2) suggested that patients with the CC genotype and C allele had increased susceptibility to HT. There were significantly higher serum levels of anti-thyroid peroxidase (ATPO) antibody in patients with the rs3761548 CC genotype (1156±163 IU/mL) compared to the other genotypes (≈582-656 IU/mL; P<0.004). We observed a greater frequency of the AC genotype in patients who had decreased ATPO antibody levels (P=0.02). Conclusions. The association of the rs3761548 SNP with risk of HT and its influence on ATPO antibody levels suggested an important role for Foxp3 in the biology and pathogenesis of HT.

Context. The grey mullet, Mugil cephalus, is an edible fish of high economic importance. Breeding biology with reference to hormonal/growth factor regulation of oocyte maturation needs to be known for its commercial production. Objective. The present study was conducted to examine the potency of maturation inducing hormones, chorionic gonadotropin (hCG), bovine-insulin, and insulin like growth factor1 (h-IGF-1) I on ovarian steroidogenesis and oocyte maturation. Design. The role of hormones and growth factors on steroidogenesis and oocyte maturation was investigated using specific inhibitors, Wortmannin for phosphatidylinositol-3 (PI3) kinase, trilostane for 3β-hydroxysteroid dehydrogenase, 1-octanol and 1-heptanol for gap junctions, actinomycin D for transcription and cycloheximide for translation of signal molecules. Methods. Actions of hormonal and growth factors were examined for steroidogenesis, by radioimmunoassay and oocyte maturation by germinal vesicle breakdown (GVBD). Specific inhibitors were used to determine the cell signaling pathways, PI3 kinase. Results. All the inhibitors attenuated the hCGinduced oocyte maturation (GVBD%), steroidogenesis including transcription, translation, gap junctions and PI3 kinase signaling. These inhibitors failed to inhibit h-IGF-I and b-insulin-induced oocyte maturation, steroidogenesis, translation and PI3 kinase signaling. Conclusion. hCG induces oocyte maturation via steroid dependent pathway involving gap junctions, transcription, translation and PI3 kinase signaling, unlike h-IGF-I and b-insulin in the mullet.

Context. Obesity is a complex and heterogeneous disorder with multiple phenotypes described. Although metabolomic biomarkers of obesity have been extensively studied, biomarkers of obesity phenotypes and differences between these phenotypes and normal-weight (NW) persons have been less investigated. Objective. The objective of this cross-sectional analysis was to investigate serum amino acids (AA) as markers of metabolic alterations in obesity phenotypes and NW. Design. Cross-sectional Subjects and Methods. By targeted metabolomics we analyzed serum samples of 70 women using ultrahighperformance liquid chromatography/mass spectrometry. Participants were divided into 3 groups: NW, metabolically healthy obesity (MHO) and metabolically unhealthy obesity (MUHO). Results. Five AAs were significantly different between study groups: cysteine, methionine, asparagine, glutamine, and lysine (p-value <0.05 and variable importance in the projection >1). Cysteine increased linearly with metabolic unwellness from NW to MUHO. Lysine and glutamine were significantly higher, and asparagine was significantly lower in NW and MHO than in MUHO. Conclusions. By trend and group analysis we identified specific changes in serum AAs along with the progression of metabolically unwellness.

Background. An increasing number of studies suggest that hypothyroidism may lead to hepatorenal toxicity. This study examined whether thymoquinone (TQ), the main active Nigella sativa constituent, could prevent the detrimental influences of hepatorenal toxicity of hypothyroidism during the juvenile period in rats. Methods. The male rats were randomly divided into four groups (n = 7), including control, propylthiouracil (PTU), PTU-TQ 5 mg/kg, and PTU-TQ 10 mg/kg. PTU was dissolved in drinking water at a concentration of 0.05% and administered for six weeks. In the PTU-TQ5 and PTU-TQ10 groups, animals received PTU plus 5 mg/kg and 10 mg/kg of the TQ (i.p.) for six weeks, respectively. The rats were evaluated after TQ treatment by measuring serum markers of liver and kidney function tests as well as oxidative stress biomarkers in liver and kidney tissues. Results. Administration of TQ (5 and 10 mg/ kg) decreased oxidative stress damage in liver and kidney tissue in hypothyroidism rats with improvement in activities of antioxidant enzymes and a decrease in MDA in both liver and kidney homogenates. Furthermore, TQ treatment significantly inhibited the elevation of serum biochemical markers of liver and kidney function associated with this hepatorenal toxicity. Conclusion. These results suggest that the protective effect of TQ in hypothyroidism-induced hepatorenal toxicity in rats is attributed to its ability to reduce oxidative stress in hepatic and renal tissues. However, more studies are recommended to investigate the exact mechanism (s) for the effect of TQ on hepatorenal outcomes of hypothyroidism in human subjects.

Context. It is unclear whether treatment is necessary for transient moderate hypocalcaemia occurring after total thyroidectomy; if it is present, it is unclear which treatment modality should be preferred. Objective. To investigate both the necessity and effectiveness of different treatment approaches of oral and/ or intravenous calcium treatment in patients with transient, postoperative, moderate hypocalcaemia. Design. This is a case control study made between June 2014 and June 2015. Subjects and Methods. Forty-five patients who had serum calcium levels 6 hours after total thyroidectomy between 7.5-8 mg/dL were divided into three equal groups: an oral calcium administration group, an intravenous calcium administration group and a no-treatment group. Serum calcium and parathyroid hormone levels were measured preoperatively and on postoperative days 1, 2, 5 and 10. Results. For post-thyroidectomy patients with serum calcium 7.5-8 mg/dL in the early postoperative period, no significant difference in serum calcium or parathyroid hormone was detected between groups. Conclusions. Follow-up without treatment seems to be the most effective approach for moderate hypocalcaemia occurring in the early period following total thyroidectomy; this suggests that intravenous treatment should be avoided.

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.

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.

Objective. This study aims to investigate the factors affecting development of acute kidney injury (AKI) in patients with severe hypothyroidism. Methods. This retrospective observational study involved patients with primary hypothyroidism and thyroid stimulating hormone (TSH) levels of more than 50 mIU/L at their review in the endocrinology outpatient clinic, between January 2015 and April 2021. Factors affecting the development of AKI were examined by logistic regression analysis. Results. A total of 100 patients, 20 (11 male (M), 9 female (F)) in the AKI (case) group and 80 (23 M, 57 F) patients in control group, were included in our study. The median age of the case group (56 years, interquartile range (IQR) 44.3–68.5) was significantly higher than the control group (49 years, IQR 32.3–60; p = 0.027), and the ratio of males to females was significantly higher in the case group (p = 0.001). Multivariate logistic regression analyses showed that hypothyroidism diagnosed after the age of 60 years (odds ratio (OR) 59.674, 95% confidence intervals (CI) 5.955–598.031; p = 0.001), free triiodothyronine (FT3) < 1.3 pg/mL (OR 17.151, 95% CI 2.491–118.089; p = 0.004) and creatine kinase (CK) > 1000 U/L (OR 1.522, 95% CI 1.602– 82.848; p = 0.015) were predictors for the development of AKI in patients with severe hypothyroidism. Conclusion. We recommend close follow-up and monitoring of patients with AKI caused by severe hypothyroidism if patients who are diagnosed at age > 60 years, CK > 1000 U/L or FT3 < 1.3 pg/mL.