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.

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.

Introduction. Fahr’s syndrome is an infrequent disorder characterized by bilateral symmetrical calcification of basal ganglia and the cerebral cortex. It can be seen genetic, idiopathic, or secondary to endocrine diseases. This disease is related to different metabolic disorders particularly with diseases of the parathyroid gland. Case 1. A 63-year-old female patient applied to our clinic due to having hypoparathyroidism with bilateral basal ganglia calcification in head computed tomography(CT). She had subtotal thyroidectomy 25 years ago. In the neurological examination, mild symmetrical parkinsonism was determined. In laboratory examination Ca:8 mg/dL (8.6- 10.2), P:5.1 mg/dL (2.3-4.5), PTH:9.53 pg/mL (15-65) were detected. Calcitriol 0.25 μ/day was added to her treatment. Her parkinsonism disappeared after the treatment. Case 2. A 49-year-old male patient was consulted when he was admitted to the department of neurology in our hospital. The physical examination demonstrated the characteristics of Albright’s hereditary osteodystrophy. The neurological examination shows bilateral symmetrical bradykinesia, dysphagia, and moderate dysarthria. In the laboratory examination PTH: 46.5 ng/L(15-65), Ca:8.6 mg/dL (8.6-10.2), P:2.7 mg/dL (2.3-4.5) were detected and were all within the normal ranges. Consequently, pseudopseudohypoparathyroidism was decided as a diagnosis. G protein alpha subunit mutation (Gsα) was not detected due to technical limitations. Conclusion. When a patient is diagnosed as Fahr’s syndrome, we should keep in mind parathyroid disorders. Fahr’s syndrome must be evaluated in patients showing intracranial calcification accompanied by parathyroid diseases.

Objective. We aimed to investigate the potential relationship between plasma alarin levels and type 2 diabetes mellitus (T2DM). Patients and Method. We included 154 participants, divided into four groups in a cross-sectional study design. The first group includes patients with T2DM without complications (n=30), the second group patients with T2DM with microvascular complications (T2DMnoC n=32), the third group patients with T2DM with macrovascular complications, T2DM-MV (n=32) and the last group is the healthy control group (n=60). Results. In our study 94 patients were diabetic; 47 females and 47 males. The control group consists of 60 people, 30 women and 30 men. It was found that these had a significant (p>0.05) variation in serum alarin levels among the T2DM (T2DM-noC=3.1±0.7 ng/mL T2DMmV=2.8±0.4 ng/mL, T2DM-MV= 3.6±0.4 ng/mL) versus control group (15.6±2.6). We failed to find a significant variation of serum alarin levels (p>0.05) between T2DM subgroups. Serum alarin levels were significantly higher among control patients (p<0.05). There was no difference between diabetic sub-groups. Conclusion. We concluded that serum alarin levels in patients with T2DM are lower than in normal people. Further studies are needed to investigate the possible prognostic value of alarin in clinical practice in T2DM.

Objective. Personal discrepancies in gastrointestinal physiology might influence responses to GH suppression during OGTT. We aim to compare growth hormone (GH) response during oral glucose tolerance test (OGTT) and intravenous glucose tolerance test (IVGTT). Methods. Data of 18 healthy volunteers were analyzed in the study. Subjects were firstly evaluated with standard 75-g OGTT. In subjects with serum glucose <100 mg/dL at basal state and <140 mg/dL at 120th minute of oral loading, IVGTT was performed after at least 3 days. Serum glucose, insulin and GH levels were measured during two tests. Results. Basal GH levels had a wide distribution ranging from 0.00005 μg/L to 0.768 μg/L (median 0.0145 μg/L). Mean nadir GH level during OGTT was obtained at 60th minute and it was 0.0376 μg/L(range 0.00011-0.387, median 0.0016 μg/L, SD: 0.095, SEM: 0.038). Nadir GH level during IVGTT was observed at 10th minute and it was 0.112 μg/L(range 0.0005-0.770 μg/L, median 0.0053 μg/L, SD: 0.242, SEM: 0.057). There was a statistically significant difference between nadir GH levels obtained during IVGTT and OGTT (p=0.028). Conclusions. We found that mean nadir GH level was significantly higher during IVGTT in healthy subjects. This is a preliminary study and further large scale studies are required to suggest that IVGTT may be used in the diagnosis and follow-up of patients with acromegaly as an alternative to or instead of OGTT.

Background. Congenital adrenal hyperplasia (CAH) is an autosomal recessive inherited disorder caused by congenital deficiency of enzymes involved in cortisol biosynthesis from cholesterol in the adrenal cortex. In this article, we aimed to present a 29-year-old female patient with I2 splice point mutation detected in one allele and P453S mutation on the other allele of CYP21A2 gene associated with 21-hydroxylase deficiency. Her further investigation revealed that her mother had P453S mutation and her father had I2 splice mutation. Case report. A 29-year-old woman with CAH was admitted to our clinic with the request of pregnancy. Her physical examination revealed a height of 151 cm, weight 59 kg, body mass index 25.8 kg/m2. According to Tanner staging, she had Stage 3 breast development and pubic hair. Her laboratory test results were as follows: Glucose: 79 mg/dL (70-100 mg/dL), Creatinine: 0.6 (0.5-0.95 mg/ dL), Sodium: 138 mEq/L (135-145 mEq/L), Potassium: 4.4 mEq/L (3.5-5.1 mEq/L), Cortisol: 0.05 μg/dL, ACTH: <5.00 pg/mL (5-46 pg/mL), 17-OH progesterone: 7.67 ng/mL (0-3 ng/mL). Chromosome analysis revealed a 46, XX karyotype. CYP21A2 gene mutation analysis was performed for the patient whose clinical history and laboratory results were compatible with congenital adrenal hyperplasia. During the reverse dot blot analysis, I2 splice mutation in one allele and P453S mutation in the other allele were detected. Conclusion. Although the I2 splice mutation detected in our case was mostly associated with a saltwasting form of CAH, it was thought that the other P453S mutation detected may explain the relatively good clinical course in our case.

Context. Exenatide is a Glucagon-like Peptide-1 receptor agonist, which is widely used for type 2 diabetes mellitus (T2DM). Limited and conflicting results are present about the effect of exenatide on the thyroid gland. Objective. The aim of this study was to evaluate the effect of exenatide treatment on structural and functional features of the thyroid gland in patients with T2DM. Design. The study was a prospective study, performed between 2015 and 2017. The laboratory values and thyroid ultrasonography features were compared before and after exenatide treatment. Subjects and Methods. The study included 39 obese diabetic patients. After inclusion to the study exenatide was started and patients were followed up for 6 months. Total thyroid volume, thyroid function tests, serum carcinoembryonic antigen (CEA) and calcitonin levels, the size and appearance of thyroid nodules were compared between baseline and after 6 months of treatment. Results. Exenatide at a dose of 5μg bid was started, increased to 10 μg bid after 4 weeks. We found a statistically significant decrease in thyroid volume (p=0.043) and serum thyroid stimulating hormone (TSH) levels (p=0.007), whereas serum ATPO. ATGl, fT4, fT3, CEA and calcitonin levels did no change with 6 months of exenatide treatment. There were no significant differences in the size and appearance of the thyroid nodules with treatment. The thyroid volume decrease was not correlated with TSH, body mass index and HbA1c reduction. Conclusion. Exenatide treatment for 6 months decreased serum TSH levels and thyroid volume, but had no effect on thyroid nodules and serum CEA and calcitonin levels.

Objective. Both obesity and periodontal diseases are significant diseases that affect the quality of life. Recent studies have focused on the relationship between obesity and periodontal disease. The aim of this study is to determine the pathophysiological relationship between obesity and periodontal disease by evaluating the clinical periodontal parameters and oxidative status. Subjects and Methods. The study included 80 individuals divided into four groups including 20 individuals in each group as following; periodontally healthy patients with normal weight, (NH), patients with chronic periodontitis and normal weight (NCP), periodontally healthy patients with obesity (OH) and patients with chronic periodontitis and obesity (OCP). Clinical periodontal parameters were recorded, and serum, saliva and gingival crevicular fluid (GCF) samples were obtained. Local and systemic levels of total antioxidant status (TAS), total oxidant status (TOS), oxidative stress index (OSI) were assessed biochemically. Results. No statistically significant difference was found among the groups regarding TAS, TOS and OSI values in serum and saliva samples (p>0.05). GCF-TAS values in NH group were statistically significantly higher compared with other groups (p<0,05) . GCF TOS values increased in obese groups (OH, OCP) compared with non-obese groups (NH, NCP) (p<0.05). Our results suggest that obesity and chronic periodontitis do not effect oxidant/antioxidant levels in serum and saliva. Conclusions. Many factors such as daily living conditions of the individual, stress and nutritional habits TAS and TOS levels of the individual may affect oxidative stress parameters. However, these factors could not be standardized in the study.

Background. Thyroid hormone resistance (RTH) is defined as a decrease in response to thyroid hormones in the target tissue. Most patients present with nonspecific findings. In this article, we aimed to represent a 22-yearold female patient who presented with palpitation, fatigue, and heat intolerance. She was thought to have thyroid hormone resistance and her genetic examination revealed NM_001128177.1 (THRβ): c.1034G > A (p.Gly345Asp) pathogenic variation in the THRβ gene. Case report. A 22-year-old female patient presented with complaints of fatigue, heat intolerance and palpitations. She was taking Propranolol twice daily at admission. Her family history revealed hypothyroidism in her grandmother. Her physical examination results were as follows: height 160 cm, weight 65 kg, body mass index 25.4kg/m2, body temperature 36.5˚C, respiratory rate 18/min, heart rate 86 beats/min, blood pressure 120/80 mmHg. Her palms were sweaty. The heart sounds were normal, and no heart murmur was auscultated. The laboratory results were TSH: 5.31uU/mL, fT3: 6.83 pg/mL, and fT4: 2.43 ng/dL. THRβ gene mutation analysis was requested for our patient whose clinical history and laboratory results were compatible with thyroid hormone resistance. The pathogenic variation NM_001128177.1(THRβ):c.1034G>A (p.Gly345Asp) was detected after analysis. Conclusion. A diagnosis of RTH requires high clinical suspicion and a genetic mutation analysis should be requested in the case of clinical suspicion. In this way, unnecessary anti-thyroid treatment can be prevented.