ACTA ENDOCRINOLOGICA (BUC)

Introduction. Autoimmunity derives from a complex interplay of genetic and environmental factors. Major histocompatibility complex (MHC) alleles and non-MHC loci have been identified as susceptibility markers. Few studies evidenced an association between autoimmune thyroid disease (ATD) and CT60 or 49 A/G polymorphisms in the CTLA-4 gene. Objectives. The aim of our research was to investigate in a pilot case-control study whether other two CTLA-4 gene polymorphisms, i.e. the CTLA-4 1661 A/G and the CTLA-4 658 C/T single nucleotide polymorphisms (SNP), are involved in genetic predisposition to ATD. Material and methods. Between January and April 2009, 42 subjects entered the study. Of these, ATD (i.e. chronic autoimmune thyroiditis, Graves’ disease) was diagnosed in 21 patients, whereas in 21 subjects no signs of autoimmunity were identified. CTLA-4 gene polymorphisms were genotyped using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Results. No association was observed between the CTLA-4 1661A/G gene polymorphism in patients with ATD and controls (p = 0.094, by chi-square test). Likewise, no statistically significant difference was noticed between groups with regard to the CTLA-4 658 C/T gene polymorphism (p = 0.649). Conclusions. At the time being, this is the first case-control study that examined and demonstrated lack of association between CTLA-4 -1661 A\G and -658 C\T SNP and ATD; however, larger numbers of subjects are needed to clarify the role of CTLA-4 gene polymorphisms in endocrine autoimmunity.

Context. SARS-CoV-2 infection was declared a pandemic in 2020 and affected millions of people worldwide. Angiotensin-converting enzyme-2 receptors, through which coronavirus enters the cells of different organs, have been detected in the thyroid gland. The most common cause of thyrotoxicosis is Graves’ disease in which thyroid-receptors antibodies (TRAb) stimulate the TSH receptor, increasing thyroid hormone production and release. Case presentation. A 22-year-old woman had symptoms of palpitation, tremor, muscle weakness, anxiety and sleep disturbance. 3 weeks before the onset of these symptoms, the patient suffered from COVID-19, which lasted 14 days and was characterized by a course of moderate severity with fever up to 38˚C, general weakness without shortness of breath. The patient had no pre-existing thyroid problems. Her TSH was <0.01 mU/L, FT4, FT3 and TRAb were increased. Antithyroid drugs, glucocorticosteroids and β-blockers were prescribed. During 3 months of treatment doses of methimazole, methylprednisolone and bisoprolol were gradually reduced due to the improvement of the patient’s condition and thyroid tests normalization. Conclusions. COVID-19 infection can cause Graves’ disease and thyrotoxicosis. The onset of this disease after SARS-CoV-2 does not depend on the presence of preexisting thyroid pathology and requires the appointment of glucocortisteroids.

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.

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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.

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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Objective. To study the effect of diethylhexyl phthalate (DEHP) alone or in combination with genistein (GEN) on the reproductive system of offspring rats, focus on the induction of reproductive outcomes. Method. 180 Wistar rats were divided in 6 groups (30 animals per group): DEHP 250 mg/kg/day group, DEHP 1000 mg/kg/day group, DEHP 2500 mg/kg/day group treated with DEHP 2500 mg/kg/day, DEHP (2500 mg/kg) + GEN (50 mg/kg) group, DEHP (2500 mg/kg) + GEN (500 mg/kg) group and control group treated with the same quantity of corn oil. The differences in sperm quality and reproductive organs were observed. Results. After DEHP administration we observed an increase in rat’s abestrus, metaestrus and all estrus cycle (P < 0.05), a decrease in rat testicle’s organ coefficient and relative energy of testis Sertoli cells and an increase in the early, late and total apoptotic rate of testicular Sertoli cells in a dose dependent manner (P < 0.05). When combine DEHP with GEN the sperm density, sperm quality, the cell activity rate and testis tissue’s changes will decrease compared with the group that receive only DEHP in a dose dependent manner. Conclusion. DEHP exposure induces cryptorchidism in offspring rats and this is aggravated by adding GEN.

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.