ACTA ENDOCRINOLOGICA (BUC)

Context. MicroRNAs (miRNAs) are short noncoding RNAs involved in posttranscriptional regulation of gene expression that influence various cellular functions including glucose and lipid metabolism and adipocyte differentiation. Objective. The aim of this study was to evaluate the levels of miR-34a and miR-149 and their relationship with metabolic parameters in obese children and adolescents. Design. Seventy children and adolescents were enrolled in the study. Plasma levels of microRNAs were evaluated by real-time PCR using SYBR green and analyzed by ΔCt method. Plasma concentrations of visfatin and insulin were measured by ELISA method. Glucose and lipid profile were determined colorimetrically. HOMA-IR was calculated and used as an index of insulin resistance (IR). Results. miR-34a was significantly lower in subjects with insulin resistance compared to obese children with normal insulin sensitivity. There was an inverse relationship between miR-34a levels and both insulin and HOMA-IR. On the other hand, miR-149 was significantly correlated with visfatin. There was no significant difference in miR-34a and miR-149 between obese and normal weight subjects. Conclusions. miR-34a is associated with insulin and HOMA-IR and thus seems to be involved in IR. miR- 149 is inversely associated with visfatin levels which could be indicative of anti-inflammatory effect of this miRNA.

The effects of daily evening melatonin (MT) injections on plasma T3 and T4 and pineal thyroxin 5’-deiodinase (5’-D) activity in euthyroid and hypothyroid rats were investigated. Circulating levels of thyroid hormones were monitored and 5’-D activity was measured in pineal homogenates throughout the daily light-dark cycle. In the euthyroid group, T3 and T4 concentrations and pineal 5’-D activity gradually increased during the L-phase of the L/D cycle to reach maximum levels early at night. The lowest values for pineal 5’-D activity and T4 were obtained later at night when endogenous MT production was the highest. MT treatment induced an opposite circadian variation of plasma T3, T4 and pineal 5’-D activity with significant increases later at night and decreases early at night vs. the control group. In the hypothyroid group, the serum T4 and T3 concentrations significantly decreased at all moments assayed. Treatment with MT did not lead to significant changes in the propylthiouracil effect on T4 and T3 levels, but maintained the biphasic response, observed in the MT treated euthyroid group. The increases induced by PTU in pineal 5’-D activity during the light phase, were reduced from 43.61 ? 2.35 ng T3/mg protein / h to 33.36?2.87 ngT3/mg protein/h (p=0.01) by MT injections. In conclusion, the results rendered the presence of the 5’-D in the rat pineal, its activity showing a circadian pattern similar to the circulating T4 levels. The MT treatment induced an opposite circadian variation of serum T3, T4 and pineal 5’-D activity suggesting an interaction between the light/dark cycle, 5’-D activity and responsiveness to MT.

Context. Angiotensin converting enzyme 2 (ACE2) is highly expressed in the kidney and cleaves angiotensin II to Angiotensin (1–7), annihilating the deleterious effects of angiotensin II which is known to be a strong activator of oxidative stress. Objective. We aimed to evaluate the relationship of oxidative stress to urinary ACE2 (uACE2) in type 2 diabetes mellitus (T2DM) patients. Design. We included consecutive normo or microalbuminuric T2DM patients in an observational transversal study. Routine laboratory investigations, plasma malondialdehyde (MDA, fluorimetric thiobarbituric method) as a marker of prooxidant capacity and superoxide dismutase (SOD, cytochrome reduction method) and catalase (CAT) activity (in erythrocyte lysate by the modification of absorbance method) as two measures of serum antioxidant capacity and uACE2 (ELISA method) were assessed. Results. MDA showed a negative correlation with SOD (r=-0.44, p=0.001), CAT (r=-0.37, p=0.006), uACE2 (r=-0.33, p=0.016) and a positive correlation with glycated haemoglobin (HbA1c) (r=0.49, p<0.001) and associated cardiovascular disease (r=0.42, p=0.001). CAT as also positively correlated to uACE2 (r=0.29, p=0.037). SOD was also negatively correlated with glycemia (r=-0.71, p<0.001) and HbA1c (r=-0.53, p<0.001). Patients with lower MDA (when divided according to median value of 3.88 nmol/ mL) had higher uACE2 57.15(40.3-71.2) pg/mL compared to 38.5(31.8-45.95) pg/mL in patients with higher MDA (p<0.001). In multivariate logistic regression uACE2 was the only predictor for MDA above or below its median (OR=0.94, 95%CI[0.90-0.98], p=0.002). Conclusion. Increased prooxidant serum capacity is associated with lower uACE2 levels in T2DM patients.

Background. Warthin-like tumor of the thyroid (WALTT) is a very rare variant of papillary thyroid cancer.We want to draw attention to this rare condition by reporting two cases. Patient reports. Patient 1 was a 24 year-old woman presented with 14×12 mm solid nodule on the left lobe of the thyroid gland. Fine needle aspiration biopsy of the nodule was reported as suspicious for papillary thyroid carcinoma. Patient 2 was a 40 year-old woman who had multinodular thyroid gland with a 31×26 mm major nodule on the left lobe. On fine neddle aspiration, cytologic findings were consistent with papillary thyroid carcinoma. Both underwent total thyroidectomy and histological examination of the cases revealed Warthin-like tumor of the thyroid. Summary and conclusion. We report two patients with WALTT. This rare variant of papillary thyroid cancinoma has four main histologic criteria: papillary architecture, oxyphilic cytoplasmic changes, papillary nuclear features and dense lymphoid infiltrate. WALTT can be distinguished from other aggressive variants with these distinct histological features. Since variants show different clinical behaviour, classification of these might be helpful to predict patient prognosis.

Objective. Adrenal incidentaloma are lesions which are stated incidentally by imaging methods when there is no suspicion of any disease in adrenal gland. Inappropriate Jak2 signaling causes some solid and hematological malignancies. But the Jak2 mutation has not been previously evaluated with regard to adrenal tumors. In this study, we aimed to positivity of the Jak2 mutation in patients with non functioning adrenal incidentaloma (NFAI). Methods. 45 (38 female–7 male) patients, who were followed due to NFAI at Tepecik Training and Research Hospital, Department of Endocrinology and Internal Medicine between February 2014 and March 2015, and 45 (31 female–14 male) healthy controls were included in the study. Results. The average age was 54.02±11.7 years and 38 patients were female, 7 were men. All patients underwent the following analyses for excluding a functioning adrenal mass, overnight dexamethasone suppression test, 24 hour urinary metanephrine and normetanephrine, plasma aldosterone/ renin activity ratio. Jak2 mutation of the patients who were diagnosed as NFAI was all negative. Conclusion. We could not identify the JAK2 gene mutation positivity in any sample. Since other possible mechanisms may throw fresh light on the etiology of adrenal incidentaloma, further clinical studies are needed on this subject.

Objective. In our study, we aimed to investigate the levels of irisin, nesfatin-1 and the relationship between levels of these relatively new molecules with cardiometabolic risk markers; carotid intima-media thickness (CIMT), epicardial adipose tissue (EAT) thickness in patients with nonfunctional adrenal incidentaloma (NFAI). Materials and Methods. Patients with NFAI (n=59) and age, sex and body mass index-matched healthy control subjects (n=59) were enrolled in this study. Serum glucose, insulin, C-reactive protein (CRP), lipid, irisin and nesfatin-1 levels and echocardiographic CIMT and EAT thickness measurements were performed in patients and controls. Results. The irisin level was 17.58 ± 4.38 pg/mL in the NFAI group, significantly higher (p<0.001) than 14.03 ± 4.03 pg/mL in the control group. Nesfatin-1 level was significantly lower in the NFAI group 194.98 ± 119.15 pg/ mL ((p < 0.001)) versus 303.48 ± 200.78 pg/mL in the control group. A positive correlation was found between irisin and nesfatin-1 levels and CIMT and EAT thickness in the NFAI group. Conclusions. In our study, we found that irisin level was higher and nesfatin-1 level was lower in patients with NFAI, and both irisin and nesfatin-1 levels were associated with CIMT and EAT thickness in NFAI patients.

Background. The pineal cytomorphological responsiveness to altered serum T4 levels awaits any comprehensive investigations in mammals .\r\nAim. The aim of the present investigation was to use rats with diversely altered serum T4 level, to study the pineal karyomorphology and functions.\r\nMaterials and Methods. Five groups each with 11 rats were used as controls and T4 (50&#956;g/100g b.w.) for seven consecutive days, thyroidectomized and kept for thirty days and additionally such TX rats, treated with T4 (50&#956;g/100g b.w.) for seven days, were used for pineal karyometry and serum T4 analysis.\r\nResults. They indicated that thyroxine administration evoked hyperactive changes in pineal gland cytomorphology along with enhanced serum T4, as evidenced from increased\r\npinealocyte nuclear diameter (&#956;m) (C 4.71+0.03,T4 5.14+0.04,p<0.001) and decreased nuclear density (C 179.44+4.78,T4 126+4.36,p<0.001) and enhanced serum T4 level\r\n(&#956;g/dL), (C 3.60+0.13,T4 13.40+1.75,p<0.001). Contrarily, thyroidectomized (TX) rats with undetectable T4 levels (<0.05 &#956;g/dL) showed pineal inhibition, as seen from significantly decreased pinealocyte nuclear diameter (&#956;m) (C 4.71+0.03,Tx 4.01+0.04,p<0.001) values, and an increased nuclear density per microscopic field (C179.44+4.78, Tx 208.8+4.47, p<0.005). However, thyroidectomized animals, supplemented with thyroxine (Tx + T4), induced pineal activation as seen from increased pinealocyte nuclear diameter, &#956;m (C 4.71+0.03, Tx + T4 5.26+0.05, p<0.001) associated with increased serum T4 level &#956;g/DL (C 3.60+0.13, Tx+T4 10.92+0.13m p<0.001).\r\nConclusion. The present study argues for a direct pineal-thyroid relationship as interpreted from cytomorphological level and hormone profiles in male albino rats.

The aim of this study is to investigate the possible association between hormonal status and adipose tissue characteristics in obese and non-obese subjects. Fourteen obese and 15 nonobese premenopausal female patients were enrolled in the study. Stromal vascular cells were isolated and cultured using modified procedures described by Entenmann and Hauner. In the non-obese group, omental SVCs seeded at a density of 4.12?1.1x103/cm2 in 25-cm2 in culture flasks for measuring cell proliferation and subcutaneus SVCs seeded at a density of 2.05?0.76x103/cm2 in 25-cm2 at culture flasks. In the obese group, omental SVCs seeded at a density of 6.11?1.98x103/cm2 in 25-cm2 at culture flasks for measuring cell proliferation and subcutaneous SVCs seeded at a density of 2.94?0.75x103/cm2 in 25-cm2 in culture flasks. Mean GPDH activity levels were significantly higher in SVCs from the omentum in obese compared to those from the omentum in nonobese (651.9?65.7 vs 405.1?60.1 mU/mg protein). However, GPDH activities were similar in SVCs from the subcutaneous SVCs in obese subjects, compared to those from the subcutaneous SVCs in non-obese subjects (303.5?63.2 vs 367.4?73.7 mU/mg protein). In obese group, omental SVCs number was positively correlated with plasma estradiol (E2) (r=0.604, p=0.017), and fasting insulin levels (r=0.843, p=0.01). It was negatively correlated with plasma progesterone (r=-0.793, p=0.006), prolactin (r=-0.655, p=0.008) and free T3 (FT3) levels(r=-0.630, p=0.01). These findings suggest that there are differences in adipose tissue proliferation capacity and metabolic activity between obese and non-obese subjects. In obese group, the number of omental stromal vascular cells was positively correlated with plasma estradiol and insulin levels.