ACTA ENDOCRINOLOGICA (BUC)

Introduction. Abnormal thyroid function affect spermato-genesis and male infertility. For men, the aromatase deficiency can cause infertility. In this study, the aim is to investigate the effect of maternal hypothyroidism on offspring testicular morphology and cytochrome-P450- aromatase (P450arom) immunoreactivity. Materials and Methods. Eighteen Wistar albino pregnant rats were divided into three groups, namely A, B and K groups. Hypothyroidism was induced by adding 0.01% of propyl thiouracil (PTU) in drinking water. Hypothyroid mothers, group A: given PTU for 21 days during pregnancy, group B: given PTU for 21 days prior to pregnancy; control mothers, group K, given only water. Hypothyroid and control group mothers’ pups at postnatal day (PND) 15 and 60 were sacrificed. We determined immunoreactivity intensity of P450arom and mRNA levels by RT-PCR performed in the testis tissues. ELISA method was used for thyroid function tests for T3, T4 and TSH. Structure of seminiferous tubule was evaluated by hematoxylin-eosin staining. Results. It was seen that the aromatase expression in 15-day-old maternal hypothyroid groups was similar to the one in the control group while there was a decline in the aromatase expression of 60-day-old groups. As for mRNA, it was determined that it had a tendency to increase over time in all groups but this increase was not significant. The tubule diameter and Johnsen’s Testicular Biopsy Score diminished in all hypothyroid groups in comparison to the control group. Conclusion. The changes that occur in the early period of testis development due to maternal hypothyroidism negatively affect testis development in the next stages of life. This situation leads to a decline in aromatase expression in the following years.

Background. Linagliptin (LNG) is a selective dipeptidyl peptidase-4 (DPP-4) inhibitor that ameliorates blood glucose control of patients with type 2 diabetes, without developing hypoglycemic risk and weight gain with a good clinical and biological tolerance profile. To the best of our knowledge, its cytotoxic, genotoxic and oxidative effects have never been studied on any cell line. Aim. To evaluate the in vitro cytotoxic, genotoxic damage potential and antioxidant/oxidant activity of LNG in cultured peripheral blood mononuclear cells (PBMC). Material and methods. After exposure to different doses (from 0.5 to 500 mg/L) of LNG, cell viability was measured by the MTT (3,(4,5-dimethylthiazol-2-yl)-2,5- diphenyltetrazolium bromide) and lactate dehydrogenase (LDH) leakage tests. The antioxidant activity was assessed by the total antioxidant capacity (TAC) and total oxidative stress (TOS) assays. To evaluate the genotoxic damage potential, chromosomal aberration (CA) frequencies and 8-oxo-2’- deoxyguanosine (8-oxo-dG) levels were determined. Results. Treatment with LNG did not cause statistically significant decreases of cell viability at lower concentrations than 100 mg/L as compared to untreated cultures. However, LNG exhibited cytotoxic action at 250 and 500 mg/L. Also, IC20 and IC50 values of LNG were determined as 8.827 and 70.307 mg/L, respectively. In addition, the oxidative analysis revealed that LNG supported antioxidant capacity at concentrations of 2.5, 5, 10, 25, 50 and 100 mg/L without generating oxidative stress. Besides, the results of CA and 8-oxo-dG assays showed in vitro nongenotoxic feature of LNG. As a conclusion, our findings clearly revealed that LNG had no cytotoxic and genotoxic actions, but exhibited antioxidative activity. In conclusion, therefore it is suggested that LNG use in diabetic patients is safe and provides protection against diabetic vascular and oxidative complications.

Purpose. The aim of the study was to investigate whether the circulating miR-132, miR-146a, miR-222, and miR-320 levels are used in the differential diagnosis of women with polycystic ovary syndrome (PCOS) and healthy women. Methods. This prospective case-control study included 50 women with PCOS and age- and body mass index- matched 50 healthy controls. The hormone and lipid profiles, levels of microRNAs (miRNAs), and parameters of carbohydrate metabolism were measured. Results. Expression levels of miRNAs were assessed using the two-step quantitative real-time polymerase chain reaction. Circulating miR-132, miR-146a and miR- 222 levels were significantly downregulated in the PCOS group compared with the control group. The miR-320 levels did not differ between the two groups. Free testosterone was negatively correlated with miR-132, miR-146a and miR-222. Insulin was negatively correlated with miR-132 and miR-146a. Conclusions. The results of the study revealed that miRNA expression, may suggest a possible distinction between healthy women and PCOS patients. miR-132, miR-146a, and miR-222 may have key functions in the pathogenesis of PCOS.

Context. Thyroid disorders are common in diabetics and related to severe diabetic complications. TRPV2 ion channels have crucial functions in insulin secretion and glucose metabolism which have an important role in the pathophysiology of diabetes. Also, they have a significant effect on various immunological events that are involved in the HT pathophysiology. Objective. This study aimed to investigate rs14039 and rs4792742 polymorphisms of the TRPV2 ion channels in type 2 diabetes mellitus (T2DM, n=100) Hashimoto thyroiditis (HT, n=70) and comorbid T2DM and HT (T2DM+HT, n=100) patients and control (n=100). Design. Case-control study Subject and Methods. RT-PCR genotyping was used to determine rs14039 and rs4792742 polymorphisms with DNA samples of subjects and appropriate primer and probes. Besides, required biochemical analyses were performed. Results. It was determined that the frequencies of the rs14039 GG homozygote polymorphic genotype and the G allele were significantly higher in T2DM+HT patients compared to the control (p=0.03 and p=0.01, respectively) and that especially the GG genotype increases the risk of T2DM+HT 3.046-fold (p=0.01, OR=3.046). It was detected that the GG genotype increased the risk of HT 2.54-fold (p=0.05, OR=2.541). TRPV2 rs4792742 polymorphisms reduce the risk of HT and T2DM+HT comorbidity almost by half and have a protective effect against HT and T2DM+HT. Conclusion. The rs14039 GG genotype of the TRPV2 gene significantly increases the risks of development of T2DM+HT and HT disorders, may have a significant role in the pathophysiology of these diseases, also leading to predisposition for their development. Conversely, rs4792742 polymorphic genotypes have a strong protective effect against the HT and T2DM+HT comorbidity.

Introduction. Primary hyperparathyroidism is diagnosed earlier and more frequently with the introduction of routine serum calcium measurements. In literature, it is shown that mortality and morbidity decrease after parathyroidectomy. In our study, we aimed to determine the effect of parathyroidectomy on oxidative stress. Materials and Methods. The results of 41 patients who underwent parathyroidectomy for primary hyperparathyroidism between March 2018 and end of December 2018 were evaluated prospectively. Total antioxidant capacity (TAC), superoxide dismutase (SOD), thiobarbituric acid reactive substances (TBARS), 8-hydroxy- 2’-deoxyguanosine (8-OHdG), malondialdehyde (MDA), parathyroid hormone, calcium and albumin were measured before and after parathyroidectomy. Results. The mean age of the patients in the study was 45 ± 13.1 years (age range: 18-76 years). The female/ male ratio was 32/9. Postoperative values of 8OHdG, MDA and SOD 1 were significantly lower than preoperative values (p <0.05). There was no significant difference between preoperative and postoperative TAC and TBARS values. Conclusion. Oxidative stress decreased in patients with primary hyperparathyroidism after parathyroidectomy. Randomized prospective studies are needed to show the relationship between biochemical and clinical parameters in order to see the clinical reflection of the study.

Introduction. Thyroid diseases may cause endothelial dysfunction. Asymmetric dimethylarginine (ADMA) levels in patients with thyroid dysfunction were analyzed by few studies.\r\nAim.We aimed to compare ADMA levels in patients with hyperthyroidism in a cohort free of cardiovascular risk associates such as diabetes or chronic renal failure with further comparison with healthy control subjects.\r\nMaterials and methods. The study took place in Duzce University Medical Faculty, Cardiology and Internal Medicine\r\nDepartment during the year 2010. The study group consisted of patients with hyperthyroidism (overt and subclinical). The patients with renal failure, diabetes and severe\r\nhypertension were excluded.\r\nResults. Mean ADMA level was 1.04 ? 0.43 &#956;mol/L in the hyperthyroid group and 0.68 ? 0.21 &#956;mol/L in the control group (p&#8804;0.001). The comparison of patients with hyperthyroidism according to the etiology (three groups as Graves?, multinodular goiter and thyroiditis) did not show any significant difference.\r\nConclusion. Asymmetric dimethylarginine increases in patients with hyperthyroidism regardless of the etiology.\r\nThe increase of ADMA levels is independent of known major cardiovascular risk factors. It may reflect the possible counteraction of endothelial dysfunction in the pathogenesis of atherosclerosis in hyperthyroidism beyond the known cardiovascular risk factors.

Background. Insulin resistance (IR) is a component of type 2 diabetes and metabolic syndrome and it increases in the presence of chronic inflammation. Lately, “neutrophilto- lymphocyte ratio” (NLR) has been used as an indicator of inflammation. This study evaluates the association between IR and NLR in obese women. Material and methods. Obese female patients who were followed up in a university hospital for the last two years were included in the study. Homeostasis model assessment of IR (HOMA-IR), C-peptide, NLR, bioelectrical impedance measurements of 83 patients were analyzed. Results. The C-peptide levels of our patients showed a highly significant correlation with HOMA-IR (p<0.001). A significant positive correlation was found between fasting plasma C-peptide levels and NLR (r=0.36 and p<0.003) in obese women. The increase in C-peptide levels had a significant effect on the increase in NLR (r2=0.31, p=0.002), however insulin had no similar effect on NLR (r2=0.01, p=0.544). Conclusion. Plasma C-peptide levels are better correlated with NLR compared to other parameters of IR. C-peptide may be used as an efficient laboratory marker with high relevance in IR and chronic inflammatory conditions in obese women.

Context. Insulin resistance has been detected in a majority of patients with polycystic ovary syndrome (PCOS). Elevated neprilysin levels are associated with insulin resistance. Objective. The present study aims to investigate plasma neprilysin and its relationship with endocrine and metabolic characteristics in patients with PCOS. Subjects and Methods. Thirty-five premenopausal PCOS patients and 35 healthy volunteers of similar age were included in the study. Demographic characteristics, biochemical and hormonal findings and also plasma neprilysin levels were determined in these patients and healthy controls. Results. In our study, HOMA-IR values were significantly higher in PCOS patients (3.3 ± 1.8) compared with the controls [(1.6 ± 1), p<0.01]. Plasma neprilysin levels were significantly higher in the PCOS group compared to the control group (1502.1 ± 1641.2 vs. 764.6 ± 562.6 pg/ mL). There was no difference in plasma neprilysin levels when PCOS patients were classified as overweight-obesity (BMI≥25kg/m2) or non-obesity (BMI<25kg/m2). Conclusion. Our findings revealed significantly higher levels for plasma neprilysin and HOMA-IR values in PCOS patients when compared to controls. No significant differences were noted between obese PCOS patients and non-obese PCOS patients in terms of plasma neprilysin levels.

Aim. To evaluate the expression of Galectin-3, Fibronectin-1, Cytokeratin-19 and HBME1 in benign and malignant thyroid nodules and to assess their diagnostic value. Methods. Immunohistochemical analysis was performed on 59 surgically removed thyroid nodules, including 34 carcinomas (12 papillary, 2 tall cell variants, 3 lymph node metastases from papillary carcinoma, 5 follicular variants of papillary carcinoma (FVPTC), 3 anaplastic, 5 follicular and 4 Hürthle cell carcinomas), as well as 25 benign lesions (10 follicular adenomas, 4 Hürthle cell adenomas, 11 nodular goiters with surrounding normal thyroid tissue).3 expression in all malignant lesions except for one case of FVPTC and one follicular carcinoma. Normal thyrocytes and the majority of the benign lesions were negative for all markers. Statistical analysis of each protein confirmed that Galectin-3 was the most sensitive (94%), followed by Cytokeratin-19 (88%). Fibronectin-1 and HBME1 proved to be less sensitive (56% and 68%, respectively), but more specific (92% specificity for each of them). Coexpression of two or more proteins was restricted to carcinomas, while their concurrent absence was highly specific for benign lesions. Comparing the immunopositivity in follicular carcinoma versus adenoma we achieved 80% sensitivity for Galectin-3 and 100% specificity for HBME1. For distinguishing the Hürthle cell lesions, Fibronectin-1 turned out to be more sensitive than Galectin-3 and Cytokeratin- 19. Conclusion. Our findings suggest that immunohistochemical panel consisting of Galectin-3, Cytokeratin-19, HBME1 and Fibronectin-1 might contribute to differential diagnosis between malignant and benign thyroid nodules, including those with follicular architecture.

Context. Papillary thyroid carcinoma (PTC) is the most common type of thyroid cancer due to its high fibrotic content; it can affect the blood flow resistance. Objective. To introduce duplex Doppler ultrasonography (DDUS) parameters of papillary thyroid carcinoma (PTC) and their correlation with size. Design. The study was designed as a prospective study. Subjects and Methods. Thyroid nodules of the patients who were already scheduled for thyroid surgery either for malignant thyroid nodules or multinodular goiter were evaluated for DDUS parameters. Size, systolic to diastolic flow velocity (S/D) ratio, pulsatility index (PI), and resistive index (RI) of each nodule were recorded. Nodules were diagnosed as PTC or benign nodules based on histopathology. DDUS parameters were compared between PTCs versus benign nodules and micro PTCs (≤ 10 mm) versus large PTCs (> 10 mm). A correlation analysis was performed between the size and DDUS parameters. Results. 140 thyroid nodules (30 PTCs, 110 benign nodules) were obtained. The mean S/D ratio, PI, and RI values were significantly higher in PTC than in benign nodules (p values were 0.0001, 0.0003, and 0.0001 respectively). The optimal cut-off values of S/D (0.732), PI (0.732), and RI (0.738) had accuracy rates of 71%, 69%, and 69%, respectively. There was no statistically significant difference between micro PTC and large PTC with regards to DDUS parameters. The size and DDUS parameters of PTC showed no significant correlation. Conclusions. PTC has a high resistive flow pattern regardless of its size; however the clinical utility of DDUS to differentiate a PTC from benign nodule is limited.