ACTA ENDOCRINOLOGICA (BUC)

No inheritance of early-onset female-related type 2 diabetes was reported within Chinese families. In this study, we aim to describe the inheritance pattern of type 2 diabetes in a 3-generation family and identify the gene responsible for type 2 diabetes. Genome-wide multipoint parametric linkage analysis revealed a maximum multipoint logarithm of odds (lod) score of 2.1 for a locus being associated with type 2 diabetes in this family on chromosome 20p11.2-12 between 23.5~30.8cM. Type 2 diabetes may be transmitted as an autosomal dominant trait with a high female-related penetrance in this family. Here we describe the first genetic locus for type 2 diabetes at chromosome 20p11.2-12. This region contains 8 known or predicted genes (PLCB1, PLCB4, LAMP5, PAK7, ANKEF1, SNAP25, SLX4IP, and JAG1). Gene SNAP25 which linked to energy or glucose homeostasis associated phenotypes may play a role in the development of type 2 diabetes in this family.

Background. Thyroid nodules are common; however, the association of two or more different tumors in the thyroid gland is unusual. We present a first case with the association of three histological types of thryroid tumors. To the best of our knowledge, this association has not been reported in the literature before. We aim here to highlight the possible coexistence of many lesions in the thyroid gland and to discuss treatment options. Case presentation. We report the case of a female patient who presented with a multinodular goiter. The final pathology after total thyroidectomy found the association of a multifocal papillary thyroid microcarcinoma arising within a Hurthle cells adenoma in a lobe and a noninvasive follicular thyroid neoplasm with papillary nuclear features in the other lobe. Due to the very low risk of recurrence, the patient was not treated with radioactive iodine. Conclusions. Many controversies remain about the management of Hurthle cells tumors and many variants of papillary thyroid carcinoma. Although the management of our case did not change, more studies are necessary to analyze the evolution of patients with multiple thyroid neoplasms. When discussing therapeutic options, the advantages and disadvantages should be considered case by case based on disease staging.

Objective. To describe the correlations between serum 25(OH) vitamin D and anthropometric and metabolic parameters in adult outpatients of both sexes with different BMI coming from an urban community. Subjects and Methods. 264 subjects referred for obesity assessment participated – 109 men and 155 women (20-60 years). Body weight and height, waist circumference (WC), blood pressure were recorded. Body composition was assessed by bioelectrical impedance (BIA) on a Tanita BC 420 MA analyzer (Tanita Inc., Japan). Serum 25(OH)D Total, Insulin, High-sensitivity C-reactive protein, blood glucose, total, HDL-cholesterol and triglycerides were measured. The insulin resistance index was calculated (HOMA-IR). Participants with BMI>25.0 kg/m2 underwent standard 75 g OGTT. Statistical analysis was performed on an IBM SPSS Statistics 19.0 for Windows platform (Chicago, IL). Results. Normal weight was found in 27.2 % of the participants, 24.6 % had overweight, 29.2 % -class I obesity, and 18.9 % – class II or III. Vitamin D was weakly and inversely correlated to different variables in the whole group – such as weight, WC, WC/Height, % body fat and HOMA-IR index (r=-0.231, -0.283, -0.307, -0.339, -0.328 respectively, all p<0.001). Building subgroups based on BMI led to loss of significance. Backward analysis revealed Total-C/LDL-C ratio, and LDL-C/HDL-C ratio as strongest predictors of serum vitamin D (p=0.001; R2=0.204). Conclusion. The association of vitamin D with blood pressure, plasma lipids, glucose and insulin is very weak on an individual level. However, several obesity indices (WC, WC/height ratio, % Body fat from BIA) might be used as a screening tool for subjects at risk for vitamin D deficiency.

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Aim. To evaluate the diagnostic performance of radiomics features of two-dimensional (2D) and threedimensional (3D) ultrasound (US) in predicting extrathyroidal extension (ETE) status in papillary thyroid carcinoma (PTC). Patients and Methods. 2D and 3D thyroid ultrasound images of 72 PTC patients confirmed by pathology were retrospectively analyzed. The patients were assigned to ETE and non-ETE. The regions of interest (ROIs) were obtained manually. From these images, a larger number of radiomic features were automatically extracted. Lastly, the diagnostic abilities of the radiomics models and a radiologist were evaluated using receiver operating characteristic (ROC) analysis. We extracted 1693 texture features firstly. Results. The area under the ROC curve (AUC) of the radiologist was 0.65. For 2D US, the mean AUC of the three classifiers separately were: 0.744 for logistic regression (LR), 0.694 for multilayer perceptron (MLP), 0.733 for support vector machines (SVM). For 3D US they were 0.876 for LR, 0.825 for MLP, 0.867 for SVM. The diagnostic efficiency of the radiomics was better than radiologist. The LR model had favorable discriminate performance with higher area under the curve. Conclusion. Radiomics based on US image had the potential to preoperatively predict ETE. Radiomics based on 3D US images presented more advantages over radiomics based on 2D US images and radiologist.

Various clinical and experimental studies indicate that gonadal hormones exert\r\nmodulatory effects on nociception and analgesia.\r\nThe aim of the present study was to investigate the role of gonadal hormones in the\r\nresponse by male and female rats to thermal nociceptive stimulation.\r\nMaterials and Methods. 7 week old albino (Wistar) rats were used in our study.\r\nAnimals were randomly divided into control, sham and ovariectomised or orchidectomised\r\ngroups. Thermal pain threshold was measured through tail immersion test before and 10, 20\r\nor 40 days after gonadectomy. The pain threshold was measured as the time required to elicit\r\na flick of the tail called analgesia time. Serum testosterone, estradiol, progesterone or\r\nprolactin levels were measured simultaneously.\r\nThe results showed that analgesia time was higher in female (5.11 min) than in male\r\n(4.93 min) intact animals (p<0.05) indicating sex difference in response to thermal\r\nnociception. Serum testosterone, estradiol or progesterone level as well as analgesia time\r\nwere not significantly reduced 10 days after gondectomy. In male animals, analgesia time\r\nwas significantly decreased (p<0.01) 20 or 40 days after orchidectomy (2.25 or 2.14 min,\r\nrespectively) compared with control rats (4.93 min). Serum testosterone concentration was\r\nsignificantly reduced (p<0.05) 20 or 40 days after orchidectomy (0.08 or 0.09 ng/mL,\r\nrespectively) compared with control serum testosterone level (2.14 ng/mL). In female rats,\r\nanalgesia time was significantly decreased (p<0.001) 20 or 40 days after ovariectomy (2.87\r\nor 2.66 min, respectively) compared with control rats (5.11 min). Serum estradiol\r\nconcentration was significantly reduced (p<0.001) 20 or 40 days after ovariectomy (3.17 or\r\n0.87 ng/mL, respectively) compared with control serum estradiol level (19.95 ng/ml). Serum\r\nprogesterone level was also decreased (p<0.001) 20 or 40 days after orchidectomy (5.27 or\r\n0.55 ng/mL, respectively) compared with control serum estradiol level (17.66 ng/mL).\r\nSerum prolactin level was not significantly enhanced during experiment indicating that there\r\nwas not heat stress influencing the procedure.\r\nConclusively, our findings clearly indicate that depletion of gonadal hormones 20 or 40 days\r\nafter gonadectomy modulates the pain-induced behavioral responses related to thermal nociception.

Context and objective. Reactive oxygen species (ROS) produced under oxidative stress is important for osteoclastogenesis. As a major member of the metallothionein (MT) family, metallothionein2 (MT2) can scavenge ROS in osteoblasts. However, the role of MT2 in osteoclastogenesis and ROS production in osteoclast precursors (OCPs) is unknown. Material and methods. In this study, we first investigated MT2 expression level in osteoporotic model mice. Next, we explored the roles of MT2 in osteoclastic differentiation and ROS production in OCPs. Ultimately, via rescue assays based on hydrogen peroxide (H2O2), the significance of ROS in MT-2-regulated osteoclastic differentiation was further elucidated. Results. Compared with sham operated (Sham) mice, ovariectomized (OVX) mice displayed bone marrow primary OCPs (Ly6C+CD11b-) having higher ROS levels and lower MT2 expression. MT2 overexpression inhibited the formation of mature osteoclasts, while MT2 knockdown was contrary. Moreover, MT2 overexpression inhibited ROS production in OCPs, while MT2 knockdown exhibited the opposite effects. Notably, the inhibitory effect of MT2 overexpression on osteoclastogenesis and ROS production was blocked by the addition of H2O2. Conclusion. MT2 inhibits osteoclastogenesis through repressing ROS production in OCPs, which indicates that the strategy of upregulating MT2 in OCPs may be applied to the clinical treatment of osteoclastic bone loss.

Context. Papillary thyroid carcinoma(PTC)s are the indolent progressive tumours. Survivin is a unique bifunctional protein with cell cycle regulation and apoptosis inhibition. The expression of this protein has been shown to be increased in thyroid tumours correlated with aggressive behavior from well differentiated to anaplastic. Objective. In this study, we aimed to investigate the relationship between immunohistochemically survivin expression and tumour-associated prognostic factors in papillary thyroid carcinomas. Design. In patients with thyroidectomy, we compared the clinicopathological findings and immunohistochemical positivity for survivin. Subjects and Methods. In 109 patients, sex, age, tumour size, histological tumour variant, tumour focality, tumour border pattern, tumour peripheral/intratumoural lymphocytic and stromal response, intraglandular spread, extrathyroideal spread, lymph node metastases, lymphocytic tiroiditis and relationships of these findings with survivin positivity were investigated. Results. When we indicated the tumour size and compared it with survivin expression, tumour size correlates with, survivin expression (p = 0.016). Survivin expression was correlated statistically significant with lymphovascular invasion, without stromal response and with intraglandular extension respectively (p<0.001, p = 0.043, p<0.001). No significant correlation was found between other clinicopathological parameters and survival. Conclusion. Few studies have investigated the relationship of survivin expression with prognosis in thyroid papillary carcinomas and showed that survivin was a poor prognostic marker. If its expression is detected in preoperative cytology smears, it may affects the surgical treatment strategy. When it is detected in the tissue, postoperative radioactive iodine treatment plan may be modified and the need for more aggressive follow-up may be considered.

Context. Patients with Cushing’s syndrome (CS) of any etiology experience a number of physical and psychological symptoms which impact negatively on healthrelated quality of life (HRQoL). Subjects and methods. HRQoL was measured using CushingQoL questionnaire. Results. The first part of our study was a crosssectional analysis of 141 patients with CS over a 10-year period. CushingQoL score was lower in pituitary CS compared to adrenal CS. Remission and older age were associated with better outcome on item 7 (physical appearance anxiety). In a multivariate regression analysis after adjustment for etiology, remission status, age, UFC, duration of hypercortisolism and presence of hypercortisolism-associated comorbidities the female gender was the only negative predictor associated with poorer outcome on each of the three scores. The presence of hypercortisolism-associated comorbidities independently predicted poorer outcome on the psychological and the global subscales. The second part of our research was a prospective study of 27 patients with adrenal adenoma. Achievement of remission independently predicted improvement of the total score of any patient. Conclusion. Studying in details and understanding the mechanisms of the impaired HRQoL in patients with CS is the only way to become aware of the problem and create methods that could help these patients.

Aim. To explore the effects and underlying mechanisms of pioglitazone (pio) on insulin sensitivity in insulin-resistant KKAy mice. Methods. Sixteen eight-week-old male KKAy mice were randomly assigned to two groups based on body weight: an insulin resistance model group and a pioglitazone treatment group (hereafter referred to as the pio-group). Eight male C57BL/6J mice were used as an insulin resistance control group. Mice in all three groups were fed an AIN-93G diet, and pio was added to the diet in the pio-group. After twelve weeks of treatment, blood glucose, serum insulin, glucose tolerance, and insulin tolerance were measured. ELISA was used to determine adiponectin and leptin in serum. A real time PCR assay was used to detect the mRNA of adiponectin and leptin in epididymal adipose tissue. A Western blot assay was used to analyze protein expression and/ or phosphorylation levels of peroxisome proliferator activated receptor γ (PPARγ), insulin receptor substrate 1 (IRS1), and protein kinase B (PKB/AKT) in the liver and epididymal adipose tissue.Results. The results showed that Pio treatment may effectively reduce levels of blood glucose and serum insulin, improve insulin tolerance and glucose tolerance, increase serum adiponectin, decrease serum leptin, and enhance mRNA expression of adiponectin in epididymal adipose tissue. Furthermore, with pio treatment, protein expression of PPARγ and phosphorylation levels of IRS1 and AKT were increased in the liver and epididymal adipose tissue. Conclusion. These results suggested that Pio intervention may ameliorate insulin resistance and improve insulin sensitivity in KKAy mice, which may be due to an increase of PPARγ and further activation of the insulin signaling transduction pathway (IRS1 and AKT) in the liver and epididymal adipose tissue of KKAy mice.