ACTA ENDOCRINOLOGICA (BUC)

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.

Context. Endothelial and vascular muscle dysfunctions are incriminated in the pathogenesis of diabetes mellitus (DM)-related vascular complications. However, the time-course of these changes remains unclear. Objective. We aimed to assess the time-dependency of changes that occur in vascular reactivity in aortic rings of rats with streptozotocin (STZ)-induced DM with shortversus long-term DM durations and in age-matched controls. Design. Wistar rats were assigned to young control (n=6), young DM (n=9), aging control (n=6), and aging DM (n=8) groups. DM was induced at 11 weeks of age using STZ (60 mg/kg, i.p.). Methods. At the end of the study (15 weeks of age for young controls and diabetics and 38 weeks of age for aging controls and diabetics), KCl - and phenylephrineinduced vascular contractility, and acetylcholine - and sodium nitroprusside (NTP)-induced relaxation were studied to assess endothelium-dependent and –independent vasodilation. Results. Young and aging controls presented similar vascular reactivity parameters. Acetylcholineinduced vasodilation was reduced in both young and aging diabetics compared to age-matched controls. Furthermore, acetylcholine-induced relaxation was significantly lower in aging compared to young diabetics. Meanwhile, NTPinduced vasodilation and both KCl- and phenylephrineinduced vasoconstriction were only diminished in aging diabetics. Conclusions. These results suggest that endothelial dysfunction is an early, progressive, event in the large arteries of diabetic rats that precedes the dysfunction of vessel musculature. The lack of any change in aortic reactivity in aging controls indicates that the changes observed in aging diabetics are probably due to prolonged, severe hyperglycemia, with a negligible participation, if any, of the advancing age.

Objective. One functional neuroendocrine tumor that causes hypoglycemia due to inappropriately high insulin production is an insulinoma. In rats, two genes coding for insulin, insulin 1 (Ins1) and insulin 2 (Ins2) are found on chromosome 1. Ins1 was produced from an Ins2 transcript, and it was inserted into the genome via an RNA-mediated duplication-transposition event, according to some structural feature analyses. Methods. In this study, the author has looked at how overexpression of the PTEN gene in the insulinoma cell line Rin- 5F affects the expression of the insulin genes, Ins 1 and Ins 2. Results. In the insulinoma cell line, overexpression of the PTEN gene boosts Ins2 gene mRNA expression but not Ins1 gene mRNA expression. It has been reported that PTEN upregulates insulin signaling by increasing insulin receptor substrate (IRS)-2 mRNA levels. Also, PTEN has been reported to be secreted in exosomes and thereafter, into extracellular space. Conclusions. The present study suggested that overexpression of PTEN might induce the increasing Ins 2 gene expression, one of the phosphorylated genes against the IRS-2 through the insulin/IGF-1 receptor. Our knowledge of the molecular pathways of PTEN relating the synthesis of insulin has been increased by the present study.

Objective. Gestational diabetes mellitus (GDM) is a common endocrine complication in pregnancy. There are few risk factors that clearly correlate with GDM. Fibroblast growth factor 21 (FGF21) is a metabolic hormone that can regulate glucose metabolism. It has been recognized that serum levels of FGF21 are significantly increased in diabetes and insulin resistance states. The objective of this study was to determine the serum FGF21 levels in women with GDM compared with non-GDM women and its correlation with insulin resistance. Methods. Thirty GDM patients and 60 healthy pregnant controls that matched for maternal and gestational age were selected. Women with previous history of GDM, hypertension, polycystic ovary syndrome, renal or liver failure and drug consumption with effects on glucose or insulin levels were excluded. FGF21 was determined and correlated with biochemical parameters of glucose metabolism and insulin resistance. Results. FGF21 concentration was significantly higher in GDM (264.5±196.2 ng/L) as compared with control groups (59.1±36.5ng/L). Correlation of FGF21 with insulin resistance was not significant. A cut-off 82.07 ng/L of FGF21 had sensitivity of 100% and specificity of 85% for prediction of GDM. Conclusion. FGF21 is increased in GDM and it is independent of insulin resistance. We suggest that FGF21 resistance could be directly involved in pathophysiology of GDM.

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Introduction. Pituitary adenomas (PA) are the third most common intracranial tumors, with an incidence rate of 10-15%. More than half are invasive, infiltrating adjacent structures. The primary objective of this project was to determine whether MGMT expression is associated with the invasiveness of PA. Material and Method. All patients who underwent surgical decompression consecutively between 2007- 2012 were included. All data were obtained from the case records. Formalin-fixed paraffin-embedded (FFPE) tissue specimens were stained with hematoxylin and eosin (HE) and then examined via light microscope. Paraffin blocks that lacked necrosis and hemorrhage were chosen for histologic examination. In addition to an immunoprofile battery that consisted of Ki-67 and p53, MGMT, S-100 and Pan-CK were evaluated as well. Results. The subjects included 25 women and 15 men. The mean age was 48.9 ± 14.5 years. Of these, 63% of cases involved the invasion of adjacent structures. Of the PA, 17 (42%) were non-functioning pituitary adenomas (NFPA). There was a statistically significant relationship between the invasiveness and Ki-67, p53, MGMT expression, and prolactinoma. Gonodotropinomas were mostly non-invasive. FPAs presented invasive features more frequently than NFPAs. Pan-CK was positive in GH-secreting adenomas but negative in FSH- and LH-secreting adenomas. Conclusion. Ki-67 and p53 in lower expression level can be used for evaluating invasiveness but not for recurrence. MGMT expression can be a useful IHC indicator for invasiveness. However, Pan-CK cannot be used for invasiveness or aggressiveness.

Background. There are scarce data about prevalence of mineral metabolism (MM) disorders in Romanian predialysis patients, so we assessed their occurrence and relationships in mild to severe chronic kidney disease (CKD). Methods. One hundred fifteen non-dialysis CKD (eGFR 31, 95% CI 29-35mL/min) and 33 matched non-CKD subjects entered this multicentric, cross-sectional study. Serum 25-hydroxyvitamin D (25OHD), intact parathyroid hormone (iPTH), phosphate (PO4), total calcium (tCa) and alkaline phosphatase (AP) were measured, along with demographic and past medical history data. Results. Hypovitaminosis D was equally prevalent in Controls and CKD (91% vs. 96% had 25OHD<30ng/mL). Increasing proportions of hyperparathyroidism (33% - stage 2 to 100% - stage 5; p<0.001) and hyperphosphatemia (2% - stage 3 to 38% - stage 5; p<0.001) were found. Hypocalcemia was more prevalent in stage 5 (25% vs. 6% in stage 4, none in stage 3 and Controls, p<0.001). Mineral metabolism parameters correlated with eGFR. In addition, iPTH was directly associated with PO4, AP, and urinary albumin-tocreatinine ratio (ACR), but inversely with tCa and 25OHD, while negative correlation of 25OHD with age, AP, ACR, and C-reactive protein emerged. In multiple regression, eGFR was the only predictor of iPTH (Beta -0.68, 95%CI -1.35 to -0.90, R2 0.46, p<0.001), whereas age and ACR were the determinants of 25OHD (a model which explained 14% of its variation). Conclusions. Hypovitaminosis D was very common irrespective of CKD presence and severity, and it seems worsened by older age and higher albuminuria. Hyperparathyroidism preceded hyperphosphatemia and hypocalcemia, and it seems mostly dependent on kidney function decline

Introduction. Subtypes of nonfunctioning pituitary adenomas which may differentiate into functioning adenomas are silent corticotroph adenomas (SCA). These are pituitary tumors positive on immunohistochemical staining for ACTH, but without clinical evidence of Cushing’s disease. Case report. FG, a 50 years old man was twice operated for compressive non secreting pituitary macroadenoma (NFPA). After the first surgery he developed hypopituitarism and needed replacement therapy for all the hormonal lines. After the second surgery he rapidly developed the clinical features of Cushing’s syndrome. Hormonal dosages showed: the absence of the circadian rhythm of cortisol, high ACTH level and the lack of suppression at 1 mg overnight and high dose Dexamethasone suppression tests. The immunohistochemistry of the previously resected pieces confirmed the diagnosis of a silent corticotroph adenoma. The patient was referred for conventional antitumoral radiotherapy associated with Cabergoline, then with Ketoconazole treatment. As the high levels of cortisol recurred, he was subjected to bilateral adrenalectomy. Conclusions. We present the rare case of a silent corticotroph macroadenoma which became hypersecreting after two pituitary adenomectomies. SCA may represent another entity in the spectrum of Cushing’s syndrome that must be evoked in the cases of pituitary macroadenomas thought to be non-functional.

recently. However, the nature of the signals that may connect body fat/muscle tissues with the central nervous system governing energy homeostasis remains to be elucidated. Objective. The present study was designed to investigate the effects of peripheral kisspeptin-10 administration on irisin release in human males. Subjects and methods. Kisspeptin-10 was administered to normal weight (n=8) and obese (n=8) men. Sequential blood sampling was performed for 30 minutes pre and 210 minutes post kisspeptin injection at 30 minutes interval. ELISA kit was used to detect plasma irisin levels. Results. There is a significant (P<0.0001) effect of Kisspeptin-10 administration on irisin release in both normal weight and obese participants. Mean irisin levels (96.24 ± 1.351 ng/mL) at 210 minutes were significantly (P<0.0001) enhanced as compared to pre-kisspeptin (59.18 ± 4.815 ng/ mL) in normal weight subjects. In obese subjects mean irisin levels (75.76 ± 4.06 ng/mL) were significantly (P<0.0001) elevated at 180 minutes post-kisspeptin when compared with pre-kisspeptin irisin levels (41.28 ± 2.89 ng/mL). Conclusion. Our findings suggest that kisspeptin may have a novel therapeutic potential to induce irisin release in humans which may have anti-obesity effects.

Purpose. Short chain fatty acids (SCFAs) play a major regulatory role in adipocyte function and metabolism. The aim of this study was to investigate the effects of SCFAs on adiponectin and leptin expression in adipocytes, and also to determine whether the effects of SCFA treatment in visceral adipocytes obtained from healthy subjects are different relative to the effects in adipocytes from patients with type 2 diabetes. Materials and Methods. Human pericardiac preadipocytes and human pericardiac preadipocytes type 2 diabetes were differentiated into adipocytes for 21 days in 48-well plates. After differentiation, two kinds of mature adipocytes, human pericardiac adipocytes (HPAd) and human pericardiac adipocytes-type 2 diabetes (HPAd-T2D) were incubated with or without 1 mM of acetic acid (AA), butyrate acid (BA), and propionic acid (PA). After 48 hours of incubation, intracellular lipid accumulation was measured using oil red staining. In addition, mRNA levels of adiponectin, leptin and Peroxisome Proliferator-Activated Receptor γ (PPARγ) were determined by Real-Time PCR system. Results. In HPAd, SCFA supplementation did not inhibit lipid accumulation. By contrast, both AA (p<0.01) and PA (p<0.01) significantly inhibited lipid accumulation in HPAd-T2D. Regarding mRNA levels of adiponectin, no significant changes were found in HPAd, while all three types of SCFAs significantly increased (p<0.05) adiponectin expression in HPAd-T2D. Leptin mRNA expression levels were significantly increased by treatment with all three types of SCFAs in both HPAd (p<0.05) and HPAd-T2D (p<0.05). Conclusion. SCFAs inhibited lipid droplet accumulation and increased mRNA expression of adiponectin and leptin in T2D-derived adipocytes.