ACTA ENDOCRINOLOGICA (BUC)

Introduction. Genetic disorders associated with the development of the pituitary gland and cranial bones may cause a genetic tendency toward Sheehan’s syndrome (SS). Our aim in this study was to investigate expression disorders in the genes responsible for the development of the pituitary gland and cranial bones in patients with SS. Materials and Methods. Forty-four patients who were previously diagnosed with SS and 43 healthy women were compared in terms of the mean expression values of genes including the prophet of PIT-1 (PROP1), HESX homeobox 1 (HESX1), POU class 1 homeobox 1 (POU1F1), LIM homeobox 3 (LHX3), LHX4, glioma-associated oncogene homolog 2 (GLI2), orthodenticle homeobox 2 (OTX2), SIX homeobox 3 (SIX3), SIX6, T-box transcription factor 19 (TBX19), transducin-like enhancer protein 1 (TLE1), TLE3, distal-less homeobox 2 (DLX2), DLX5, MSH homeobox 2 (MSX2), and paired box 3 (PAX3). Results. The mean expression values of the HESX1, TLE1, TLE3, and MSX2 genes were significantly different in the SS group from the healthy control group, while the mean expression values of the remaining genes were similar. Conclusion. The present study concludes that abnormal expressions of HESX1, TLE1, TLE3, and MSX2 genes may cause a genetic predisposition to the development of SS.

Hypoparathyroidism is a disease characterized by low serum calcium and inappropriate low parathyroid hormone (PTH) levels. Common therapy for chronic hypoparathyroidism usually includes oral calcium and activated vitamin D supplementation (calcitriol), hypoparathyroidism being the one of few endocrine disorders not replaced by the missing hormone. In January 2015, FDA approved PTH (1-84) for the treatment of hypoparathyroidism in patients who cannot be well-controlled on calcium and active forms of vitamin D alone and for whom the potential benefits are considered to outweigh this potential risk. Until now, there are 4 phase 3 clinical trials investigating the role of human recombinant PTH (1-84) for the treatment of hyopoparathyroidism: Replace, Race, Relay, and Repeat. These studies demonstrated a more than 50% reduction in calcium and active vitamin D requirements. Future strategies for the treatment of hypoparathyroidism could be stem cell therapy recombinant with PTH and viral or nonviral factors or parathyroid gland transplantation.

Background. Thyroid nodules stiffness may predict thyroid malignancy. Objectives. The purpose of the study was to investigate the diagnostic value, interobserver agreement and reliability of real time ultrasound elastography (USE) when assessing solid thyroid nodules. Design. A prospective, observational study in a tertiary center. Subjects and Methods. In 49 patients scheduled for thyroidectomy, a senior radiologist and two radiologists in training independently assessed 81 solid thyroid nodules with USE using a 6600 Hitachi machine. Pathology results were used as a reference standard. Nodule stiffness was evaluated using the Asteria scoring system. The diagnostic ability of the elastography scores for the assessment of the thyroid solid nodules was evaluated using AUROC (area under the receiver operating characteristic curve) analysis. The Cohen’s kappa (k) values were used for interobserver agreement evaluation and interclass correlation coefficient (ICC) was used as a measure of reliability. Results. Pathology results revealed 20 papillary carcinomas and 61 benign nodules. The elastography identification of malignant nodules by the senior radiologist was performed with an AUROC of 0.84 [95% Confidence interval (CI) 0.74-0.91], with Sensitivity= 100%, and Specificity= 68.85%. When performed by ultrasound operators in training, the diagnostic performance slightly decreased. With no statistically significant difference between the diagnostic performance of the three readers, USE demonstrated good inter-observer agreement and good reliability (ICC= 0.81). Conclusion. USE may be an accurate tool of assessment for solid thyroid nodules, identifying with high sensitivity the malignant ones, particularly micronodules. USE is reproducible and reliable when used both by experienced operators and medical professionals in training.

Background. Hashimoto thyroiditis (HT) is an autoimmune disorder associated with hypothyroidism. Lymphocyte infiltration leading to thyroid follicular cell destruction is counteracted by increased collagen production, deposition and scarring. However, only recently a specific subpopulation of modified fibroblasts with contractile properties, namely “myofibroblasts” (MFBs) have been linked to HT. Aim. Our ultrastructural study aims to delineate the presence and contribution of MFBs to the fibrotic milieu of HT. Material and Methods. Tissue biopsies were obtained from 5 HT-diagnosed patients and specimens were examined using a Transmission Electron Microscope (TEM). Results. Histopathological examination indicated extensive microvilli atrophy and atypical vacuolations of the thyroid follicular cells in the HT samples. In addition to interstitial extravasated lymphocytes, capillaries were encircled by MFBs (mean distance from lumen 1.248± 0.43μm) with the characteristic electron-dense α-smooth muscle actin (α-SMA), confirmable in higher magnifications. Myofibroblastic projections were found to have significantly higher representation near the capillary lumen compared to the impaired endothelial lining (P < 0.01). Conclusion. Our TEM findings suggest that the intrusion of endothelia by myofibroblastic projections can be a significant factor towards the malfunction of follicular cells in HT patients and offer a paradigmal understanding of the ultrastructural interactions that may underlie the HT pathology.

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Background. Retinopathy is a common complication of diabetes and strongly related to the duration of the disease and the quality of its management. Despite this relationship, some studies have reported the prevalence of diabetic retinopathy at diagnosis to be 5-30%.\r\nAim. To investigate the prevalence of retinopathy in patients with newly diagnosed type 2 diabetes and its relation to some association factors in Isfahan, Iran.\r\nMethods. During 2001-2004, all newly diagnosed type 2 diabetics (n= 710) attending Isfahan Endocrine and Metabolism Research Center, were enrolled, by consecutive patient selection. Everybody accepted our invitation. The patients were examined by an internist and then by an ophthalmologist for retinopathy. Fasting plasma glucose, glycosylated hemoglobin, lipid profile, and 24-hour urinary albumin and creatinine concentrations were measured.\r\nResults. Of 710 patients, 286 were male. Mean age of the patients was 48.8(9.8) years (31-72 years) and median of diabetes duration was 6 months (0.5-12 months), respectively. Nine percent of patients (CI95%: 7-11) [(9.8% of men (CI95%: 6-13) and 8.5% of women (CI95%: 6-11)] had retinopathy (Odds ratio= 0.85, CI95%: 0.51-1.43, P= 0.5). In the final analysis using logistic regression test, body mass index (OR= 0.9, CI 95%: 0.8-1, P= 0.01), diastolic hypertension (OR= 3.9, CI 95%: 1.33-11.7, P= 0.01) and 24-hour urinary albumin concentration (OR= 1.005, CI 95%: 1-1.01, P= 0.01) were identified as association factors\r\nfor retinopathy.\r\nConclusions. Retinopathy was moderately prevalent in our patients.

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Context. State of art imaging techniques might be a useful tool to early detect the retinal vessels lesions in diabetes. Objective and design. This analytical observational study investigates the retinal microcirculation changes in type I and II diabetic patients without retinopathy using adaptive optics ophthalmoscopy (AOO) and optical coherence ophthalmoscopy angiography (OCTA). Subjects and methods. Fifty-five subjects were included in this study and were divided in three groups: type I diabetic group (n=16), type II diabetic group (n=19) and control group (n=20). An adaptive optics retinal camera was used to assess the parameters of the temporal superior retinal arterioles. Moreover, vessel density of the superficial capillary plexus across the parafoveal area was measured with OCT-A. All cases were investigated once, in a cross-sectional design. Results. Diabetic patients from both groups had a higher wall-to-lumen-ratio compared to the controls (p=0.01 and 0.01, respectively). Interestingly, no significant differences were found between the two diabetic groups (p=0.69). Moreover, the vessel density was smaller in the type I diabetic group than in the control group (p=0.001) Conclusion. AOO might be a useful tool to detect early retinal vascular changes in diabetes before any clinical signs and together with OCTA it might bring important information on the prognostic and pathophysiology of the disease.

Context. Retinal microvascular dysfunction differs in macular edema lesions in the two eyes of the same patient with diabetic retinopathy. Objective. To evaluate the relationship between central macular thickness (CMT) and metabolic/systemic factors including anthropometric and laboratory findings, in patients with regressed diabetic retinopathy and a history of pars plana vitrectomy (PPV) combined with internal limiting membrane peeling in one eye. Subjects and Methods. Forty-two eyes with PPV and the same patients’ fellow 42 eyes (without PPV) included this study. Fasting blood samples of these 42 diabetics were collected to study adiponectin levels and other routine parameters. Results. The average hemoglobinA1c value was 7.3±1.3%. CMT of the vitrectomized eyes were significantly correlated with atherogenic index of plasma, total cholesterol, low density lipoprotein cholesterol and uric acid (UA). On the other hand, CMT of the nonvitrectomized fellow eyes significantly correlated with glucose levels and diabetes duration. Adiponectin, adiponectin/body mass index, adiponectin/fibrinogen were found significantly higher in the subgroup with CMT≥300µm in the vitrectomized eyes (P<0.05). UA levels were higher in the subgroup with CMT≥300µm in the fellow (nonvitrectomized) eyes (P<0.05). Conclusions. Although there was no relationship between CMT and hemoglobinA1c values, CMT seemed to be affected by atherogenicity, prooxidant chemical alterations in the course of inflammation, so determination of adiponectin and UA levels may be suggested before surgery to predict the atherosclerotic damage and the postoperative CMT value. Vitrectomy performed at the proper time may be helpful in metabolic remodeling process of the retinal tissue along with life style changes, well control of diabetes, and intraocular treatments.

Context. Polycystic ovarian syndrome (PCOS) is commonly associated with obesity, but the prevalence of the syndrome in obese patients is not well established. Objective. The present study aims to investigate the prevalence of PCOS among overweight and obese premenopausal women and to evaluate the possible associations between the syndrome and metabolic disturbances in obese patients. Methods. Medical records of all women referred to a single endocrine center because of obesity and/or metabolic disturbances during a three-year period were analyzed. A total of 262 overweight and obese patients of reproductive age were included in the retrospective study. Results. The overall prevalence of PCOS using the Rotterdam criteria in the group of overweight and obese women was 26%. The degree of obesity did not influence the PCOS prevalence. Women with PCOS had higher blood glucose and insulin levels after glucose load in comparison to other obese patients despite the younger age. Conclusions. PCOS is a common finding among obese women seeking endocrine help. The oral glucose tolerance test is an important tool for the early detection of carbohydrate disorders in women with the syndrome. Furthermore, screening for PCOS components might be justified in young obese women with pronounced insulin resistance or dysglycemia.