ACTA ENDOCRINOLOGICA (BUC)

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.

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.

Objective. We aimed to investigate whether lifestyle and body fat mass have an impact on the occurence of nonfunctional adrenal incidentalomas (NFAI). Methods. 100 patients with NFAI were included . 50 people constituted the control group. Physical activities of these groups were evaluated (using the International Physical Activity Questionnaire), smoking status was determined, anthropometric measurements were made. Body fat mass, fat percentage, total body water and fat free mass were measured using bioelectrical impedance method. Results. Body mass index (BMI), waist, hip, neck circumference, total body fat percentage and fat mass and smoking rate were found to be statistically higher in the patient group. Physical activities did not differ significantly. When a subgroup with similar age and BMI among was created, waist circumference and total fat mass were again significantly higher in the patient group. There was a significant positive correlation between the size of the adrenal mass and waist, neck circumference, BMI, and cortisol after 1 mg dexamethasone suppression test. Conclusion. The increase in the fat mass may have an impact on the development of NFAI. Although the patients were regarded as nonfunctional, suppressibility of the cortisol decreases as the mass size of the incidentaloma increases.

Objective. To characterize serum chemerin levels in obese patients with gestational diabetes mellitus (GDM). Design. Case–control study. Subjects and Methods. Forty seven obese women with newly diagnosed GDM at 24-28 weeks of pregnancy and 32 age, body mass index- and gestational age-matched, normal pregnant women were included. Metabolic patterns and serum chemerin concentrations were measured. Results. Serum chemerin levels were significantly higher in subjects with GDM as compared to healthy pregnant controls (p < 0.05). Fasting insulin was similar between the two groups. HOMA-IR tended to be higher in GDM group but did not reach statistical significance. Women with GDM had significantly higher triglyceride (p < 0.01) and lower highdensity lipoprotein cholesterol (p < 0.001) than controls. In multiple linear regression analyses, chemerin was significantly associated with BMI (beta-coefficient = 0.274, p = 0.01), HbA1c (beta-coefficient = 0.327, p < 0.01), HDL-cholesterol (beta-coefficient = -0.307, p < 0.01), triglyceride (betacoefficient = 0.236, p < 0.05), insulin levels (beta-coefficient = 0.236, p < 0.05) and HOMA index (beta-coefficient = 0.283, p = 0.01). Conclusions. Maternal chemerin levels were significantly increased in GDM at 24-28 weeks of pregnancy. The physiological significance of elevated serum chemerin in GDM remains unclear.

Context. The relationship between life changes and glycemic control in children with type 1 diabetes during the pandemic period was examined. Objective. We aimed to investigate the effect of the pandemic period on 66 children (aged 5-18 years) with type 1 diabetes using scales evaluating family functionality, nutritional habits, adherence to treatment and depression status. Design. It is a cross-sectional clinical and laboratory study using certain scales for its descriptive features. Subjects and Methods. Demographic characteristics, anthropometric measurements, laboratory investigations were evaluated. Family functionality of the patients were evaluated with Smilkstein’s family APGAR scale, motivation and knowledge levels were evaluated with the 6-item Morisky medication adherence scale (MMAS-6), nutritional habits were evaluated with the Mediterranean diet quality index (KIDMED), and depression status was evaluated with the children depression inventory (CDI). Results. The mean HbA1c level increased significantly in the first year of the pandemic compared to the onset of the pandemic period (8.5% vs. 8.9%, p: 0.003). In the responses to these scales, children with diabetes have high family functionality (89.4%), high motivation (90.9%) and high knowledge level about adherence to treatment (97%). Furthermore, healthy eating habits (high KIDMED index scores 92.4%), and low degree of depression score (95.5%) have been observed. We detected a statistically significant positive correlation between HbA1c and CDI scores (r: 0.27; p: 0.02), and a negative correlation between HbA1c and MMAS-6 motivation score (r: -0.30; p: 0.01). Conclusions. In this study, the effect of motivation and mood changes on glycemic control was more clearly demonstrated.

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.

Context. Subacute thyroiditis is an inflammatory thyroid disease, which is treated by nonsteroidal antiinflammatory drugs (NSAIDs) or steroids. Objective. Defining characteristics of patients with subacute thyroiditis at diagnosis and during follow-up. Investigating the efficacies of NSAID and different doses of steroids and their effects on rates of relapse, recurrence, development of hypothyroidism and on quality of life and sleep parameters. Design. A 3-year observational study in a tertiary referral center. Subjects and Methods. A total of 63 patients with subacute thyroiditis were included. Clinical outcomes of patients treated with NSAIDs and NSAID unresponsive patients treated with prednisolone with initial doses of 0.5 mg/kg/day and 15 mg/day were evaluated. Results. White blood cell count at diagnosis was an independent predictor of NSAID unresponsiveness. No relapse or recurrence was observed in patients receiving low dose of steroids. Long symptom duration until diagnosis and treatment with NSAIDs were associated with development of hypothyroidism. Subacute thyroiditis caused significant deterioration in quality of life and sleep of patients and low dose of steroid was as effective as higher doses in improving these parameters. Conclusions. For patients with no response to NSAID therapy, an initial low dose of prednisolone (15 mg/ day) is determined as a safe treatment method when dose reduction is performed with appropriate timing.

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.

Purpose. To investigate the association between papillary thyroid cancer (PTC) and Hashimoto’s thyroiditis (HT). Design. This study is a retrospective study that conducted during 7 consecutive years with a median 119.5 months follow-up. Subjects and Method. Patients who underwent thyroidectomy in Dokuz Eylül University Hospital during 7 consecutive years were included. Patients’ demographics, biochemical, radiological, and pathological results were retrospectively assessed. Results. Four hundred sixty nine patients were evaluated. Among 469 patients who underwent thyroidectomy, 132 (28.1%) were malignant, while 182 patients were diagnosed with HT (38.8%). PTC was ranked first at 92.4% (n: 122). The prevalence of HT was 54.9% in patients with PTC and 33.1% in patients without PTC diagnosis (p<0.001). Younger age and the presence of HT were independently associated with PTC. The presence of HT was associated with increased risk of development of PTC (OR: 2.2, %95 CI: 1.4-3.5, p<0.001) but not with TNM stage or recurrence. Lymph node metastasis at presentation was the strongest predictor of recurrence (OR: 13.9, CI: 3.5-54.6, p<0.001) Conclusions. HT was an independent risk factor for development of PTC. According to our findings, HT patients (particularly with nodular HT) should be observed carefully and thyroid fine needle aspiration biopsy (TFNAB) should be encouraged if necessary.

Aim. To evaluate the malignancy rates of Atypia of undetermined significance /follicular lesion of undetermined significance (AUS/FLUS) cases in the light of clinical and sonographic features. Material and Methods. The percentage of AUS/ FLUS cases, second fine needle aspiration cytology (FNAC) results, cyto-histopathological correlations and risk of malignancy were analyzed. Results. 113 out of 1461 thyroid FNAC samples (7.7%) were diagnosed as AUS/FLUS and included in the study. Seventy three out of 113 cases (64.6 %) underwent repeat biopsies or surgery. From 45 cases repeat biopsies were taken and 28 had thyroidectomy or lobectomy. There was a significant relation between nodule size and underwent surgery or repeat FNAC (p=0.036). Malignancy rate was 24.6% for cases which had any managements. The malignancy rates were higher in AUS/FLUS cases with cytological atypia (28.8%). After surgery the most common malignancy was papillary thyroid carcinoma, followed by follicular carcinoma. Conclusion. The risk of malignancy of AUS/ FLUS cases is quite high because of the heterogeneity of the group. The sub-classification of this category according to cytological or/and architecture atypia may be more useful in predicting malignancy risk. Further larger studies with ancillary techniques including molecular analysis may be more useful in determining the malignancy risk and appropriate management of this heterogeneous category.