The International Journal of Romanian Society of Endocrinology / Registered in 1938

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  • General Endocrinology

    Yildirim AB, Ozdamar S, Kaymak E

    The Effects of Maternal Hypothyroidism on the Immunoreactivity of Cytochrome P450 Aromatase in the Postnatal Rat Testicles

    Acta Endo (Buc) 2017 13(1): 7-16 doi: 10.4183/aeb.2017.7

    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.
  • General Endocrinology

    Cadirci K, Turkez H, Ozdemir O

    The In Vitro Cytotoxicity, Genotoxicity and Oxidative Damage Potential of the Oral Dipeptidyl Peptidase-4 Inhibitor, Linagliptin, on Cultured Human Mononuclear Blood Cells

    Acta Endo (Buc) 2019 15(1): 9-15 doi: 10.4183/aeb.2019.9

    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.
  • General Endocrinology

    Bulut Arikan F, Ozdemir FA, Sen D, Erdem S, Yorubulut S, Dogan H, Keskin L

    TRPV2 Polymorphisms Change the Risk of Type 2 Diabetes - Hashimoto Thyroiditis Comorbidity

    Acta Endo (Buc) 2020 16(1): 15-21 doi: 10.4183/aeb.2020.15

    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.
  • General Endocrinology

    Alcelik A, Ozhan H, Gurses Alcelik A, Yalcin S, Aydin Y

    Asymmetric Dimethyl Arginine Level as a Cardiovascular Risk Factor in Patients with Hyperthyroidism

    Acta Endo (Buc) 2012 8(1): 27-34 doi: 10.4183/aeb.2012.27

    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 μmol/L in the hyperthyroid group and 0.68 ? 0.21 μmol/L in the control group (p≤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.
  • General Endocrinology

    Siderova M, Hristozov K., Krasnaliev I., Softova E., Boeva E

    Application of immunohistochemical markers in the differential diagnosis of thyroid tumors

    Acta Endo (Buc) 2013 9(1): 41-51 doi: 10.4183/aeb.2013.41

    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.
  • Endocrine Care

    Aslan A, Sancak S, Aslan M, Ayaz E, Inan I, Ozkanli SS, Alimoglu O, Yikilmaz A

    Diagnostic Value of Duplex Doppler Ultrasound Parameters in Papillary Thyroid Carcinoma

    Acta Endo (Buc) 2018 14(1): 43-48 doi: 10.4183/aeb.2018.43

    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.
  • Endocrine Care

    Okuroglu N, Ozturk A, Ozdemir A

    Is Iron Deficiency a Risk Factor for the Development of Thyroid Autoantibodies in Euthyroid Women with Reproductive Ages?

    Acta Endo (Buc) 2020 16(1): 49-52 doi: 10.4183/aeb.2020.49

    sitive period in terms of thyroid hypofunction. Iron deficiency has been associated with both thyroid function and thyroid autoimmunity. Objective. We aimed to investigate whether iron deficiency is a risk factor for thyroid autoimmunity in nonpregnant women at childbearing age. Design. This cross- sectional study was conducted in non-pregnant women who presented to the Internal Medicine Policlinic between January 2018 and December 2018 in the University of Health Sciences “Fatih Sultan Mehmet” Training and Research Hospital. Methods. Three hundred fifty-eight non-pregnant women of reproductive ages (203 iron deficient-ID, 155 control) participated in this study. Women with known thyroid disease, currently undergoing treatment for thyroid disease or whose thyroid function tests were outside the reference range were excluded from the study. Blood sample was taken after at least 8-10 hours of fasting for measurement of serum iron (Fe), total iron binding capacity (TIBC), serum ferritin (SF), whole blood count, thyroid function tests (fT4, TSH), anti-thyroid peroxidase antibodies (TPOAb) and anti-thyroglobulin antibody (TgAb). The patients with SF levels ≤ 15 ng/dL were accepted as iron deficiency. Results. The group with ID had higher TSH and lower T4 values that did not reach statistical significance compared to the control group (p=0.101 and p=0.098, respectively). Antibody positivity was more frequent in the ID group than in the control group (35.96% vs. 20.65%, p = 0.002). Conclusions. Iron deficiency is associated with thyroid autoimmunity and it should be considered as a risk factor for screening thyroid antibody, particularly in pregnancy planning women.
  • Endocrine Care

    Ozer OF, Kacar O, Demirci O, Eren YS, Bilsel AS

    Plasma Concentrations and Correlations of Natriuretic Peptides and Oxytocin During Labor and Early Postpartum Period

    Acta Endo (Buc) 2017 13(1): 65-71 doi: 10.4183/aeb.2017.65

    Context. Natriuretic peptides (NP) and oxytocin (OT) play an important role in cardiovascular and hydroelectrolytic homeostasis. Changes in NP levels and their roles in cardiovascular adaptations in pregnancy and labor have not been clear. Objective. The present study aimed to investigate the changes and correlations in plasma levels of atrial natriuretic peptide (ANP), C-type natriuretic peptide (CNP), B-type natriuretic peptide (BNP) and OT during labor and the postpartum period. Study design. Blood samples were collected from 29 healthy pregnant women in the active phase of spontaneous labor, 15 minutes after delivery and 3 hours postpartum. Plasma levels of OT and the stable N-terminal fragments of NPs (NT-proANP, NT-proCNP, NT-proBNP) were measured using enzyme or electrochemiluminescence immunoassays. Results. The plasma levels of NT-proANP and NTproCNP significantly decrease 3 hours postpartum compared to the active phase of labor and to 15 minutes after delivery. The plasma NT-proBNP levels significantly higher after delivery and 3 hours postpartum compared to the active phase of labor. A significant correlation exists between OT and NTproANP levels during the active phase of labor and 15 minutes after delivery. Conclusions. The data show that during labor and postpartum, the plasma concentrations of the NPs change differently. Elevations in NT- proBNP after delivery suggest that BNP may be involved in postpartum adaptations. The correlations between OT and ANP levels indicate that OT may be partly responsible for the increased levels of ANP and may have a role in the modification of the cardiovascular system.
  • Endocrine Care

    Ordu S, Gungor A, Yuksel H, Alemdar R, Ozhan H, Yazici M, Albayrak S

    The impact of pioglitazone therapy on glycemic control, blood pressure and inflammatory markers in patients with diabetes mellitus

    Acta Endo (Buc) 2010 6(1): 73-82 doi: 10.4183/aeb.2010.73

    Aim. The aim of our study was to investigate the effect of pioglitazone on glycemic and blood pressure control, on inflammation markers in diabetic patients.\r\nPatients and methods. Forty-nine diabetic patients who had been followed up as outpatients for 2.7 years and HbA1c was >7% were included in the study. The patients had never received thiazolidinedione therapy before. Clinical, metabolic variables, high-sensitive Creactive protein (hsCRP), homocysteine (HCY) and asymmetric dimethylarginine (ADMA) levels were measured. 30 mg pioglitazone were administered. The patients were followed up for six months and all the measurements were re-evaluated for comparison.\r\nResults. Body mass index (BMI) significantly increased after treatment. Fasting glucose, HbA1c and HsCRP were decreased. Insulin resistance was improved and HOMA-IR index was decreased after pioglitazone treatment [8 (?6.5) vs 4(?3.1); p<0.0001]. Pioglitazone improved lipid metabolism. Mean total cholesterol and LDL cholesterol levels were decreased and HDL cholesterol was increased after treatment. The decrease in triglyceride and homocysteine levels did not reach significance. Mean ADMA level did not change after therapy [0.62 (?0.39) vs 0.61 (?0.44); p=0.85].\r\nConclusion. Pioglitazone treatment in type 2 DM produced significant improvements in measures of glycemic control, plasma lipids, blood pressure and homocysteine levels. Pioglitazone had no influence on ADMA levels.
  • Editorial

    Ekinci I, Hursitoglu M, Tunc M, Kazezoglu C, Isiksacan N, Yurt S, Akdeniz E, Eroz E, Kumbasar A

    Adrenocortical System Hormones in Non-Critically ill Covid-19 Patients

    Acta Endo (Buc) 2021 17(1): 83-89 doi: 10.4183/aeb.2021.83

    Context. The effects of COVID-19 on the adrenocortical system and its hormones are not well known. Objectives. We studied serum cortisol, serum adrenocorticotropic hormone (ACTH), and their ratio in hospitalized non-critically ill COVID-19 patients. Design. A prospective case-control study. Methods. The study participants were divided into 2 groups. Group 1 consisted of 74 COVID-19 patients. The second group consisted of 33 healthy persons. Early admission above hormones levels was determined and compared between the study groups. Besides that, COVID-19 patients were grouped according to their Glasgow Coma Score (GCS), CURB-65 score, and intensive care unit (ICU) requirement, and further sub-analyses were performed. Results. There were no significant differences in the mean age or gender distribution in both groups. In the patients’ group, the serum ACTH concentration was lower than in the healthy group (p<0.05). On the other hand, the serum cortisol levels and cortisol/ACTH ratio of the patients’ group were significantly higher than of the healthy controls (p<0.05, all). Further analyses showed that, although serum cortisol and ACTH levels were not high, the cortisol/ACTH ratio was higher in COVID-19 patients with low GCS (<15) than patients with normal GCS (=15) (p<0.05). In COVID-19 in patients with different CURB-65 scores, the cortisol/ACTH ratio was significantly different (p<0.05), while serum cortisol and ACTH were not different in groups (p>0.05). Serum cortisol levels and cortisol/ACTH ratio were higher but ACTH level was lower in the ICU needed COVID-19 patients than in patients who do not need ICU (p<0.05). Conclusion. Our pilot study results showed that the cortisol/ACTH ratio would be more useful than serum cortisol and/or ACTH levels alone in evaluating the adrenocortical system of COVID-19 patients. Still, further detailed studies are needed to confirm these.