ACTA ENDOCRINOLOGICA (BUC)

Context. Adipokines secreted by fat cells are vital to the control of energy metabolism, communicating the nutrient status with the tissues responsible for controlling both energy intake and expenditure and insulin sensitivity. Objective. We aimed to prove in an experimental animal study that maternal obesity has long term adverse fetal metabolic consequences, which pass on even to the next generation of descendants. Design. The effects of maternal obesity have been studied on animal model using 50 obese female Wistar rats, in which we induced obesity by high-calorie high-fat diet administered by gavage. Subjects and Methods. Obese rat females were sacrificed at gestation term and we analyzed the secretion of adipokines from maternal venous blood: leptin and adiponectin, placental, pancreatic, liver and brain homogenates lipid peroxidation levels estimated by: MDA (malonyl-dialdehyde), total thiols and GSH – as antioxidant factors and routine biochemistry. Results. Low levels of adiponectin and increased levels of leptin positively correlated with the value of placental and fetal tissue lipid peroxidation (from the liver, pancreas and brain) measured by elevated MDA and total thiols and low levels of GSH. The lipid peroxidation in the organs examined generated consistent results, showing high levels of peroxidation expressed through high values of MDA in the groups with Omega 6 supplements respectively no supplementation, and low levels of antioxidants expressed through glutathione and thiols. Conclusions. Endocrine secretion of adipokines from the adipocytes and the recruited macrophages of obese mothers is positively correlated with placental and tissue lipid peroxidation level and routine biochemical parameters.

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.

Context. Neoangiogenesis and lymphangiogenesis are essential for the growth of tumor and progression of malignancy. Objective. The study examined the significance of VEGF-C expression in comparison to classical prognostic factors in differentiated thyroid carcinoma (DTC), as well as an independent prognostic marker in DTC. Design. The study included 81 patients with DTC allocated in two groups according to the type of cancer (follicular versus papillary) and then compared to expression of VEGF-C and clinicopathological features. Methods. Expression of VEGF-C was identified with anti-VEGF-C antibody using tris-EDTA buffer Antigen Retrieval Protocol. Each specimen was scored with a semiquantitative score system (H-score). Results. The analysis of T staging system showed a linear correlation between the size of a tumor, expression of VEGF-C and recurrence of a disease, with a statistical significance (p < 0.0001). There was a clear and significant correlation between VEGF-C expression and T stage in patients with papillary carcinoma (p = 0.0294). Analysis of invasion of a surgical margin demonstrated significant positivity in patients with papillary thyroid cancers who expressed VEGF-C (p = 0.0207) indicating the worse prognosis of a disease. Also a statistically significant correlation was between VEGF-C and extrathyroid extension, indicating the worse prognosis (p = 0.0133) in papillary cancers. The level of VEGF-C expression was statistically significant in patients with papillary thyroid cancer (p = 0.039). Conclusions. This study undoubtedly demonstrates that VEGF-C expression is an evident negative prognostic factor in patients with papillary thyroid carcinoma, along with the classic prognostic factors, such as a larger tumor size, tumor margin involvement, extrathyroid extension, i.e. local aggressiveness.

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.

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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.

Objective. Type 2 diabetes mellitus (T2DM) is a major health problem worldwide. Earlier studies have reported that pancreatic fat content (PFC) and liver fat content (LFC) are risk factors for T2DM. The aim of the present study was to demonstrate the relationship between PFC, LFC and T2DM. Methods. A total of 70 T2DM subjects and 30 nondiabetic volunteers who underwent Dixon-based magnetic resonance imaging (MRI) method at Yixing People’s Hospital between December 2018 to December 2020 were included in the study. The three-point Dixon (3p-Dixon) method was used to measure the fat content in the pancreas and liver. Clinical indices including gender, age, body mass index (BMI), total cholesterol, triglyceride, glucose and C peptide levels were collected. The association between PFC, LFC, and OGTT-derived parameters was examined by Pearson and Spearman correlation analyses. Results. T2DM subjects had higher PFC and LFC than those measured in the non-diabetic subjects (p <0.05). PFC and LFC were associated positively with OGTT-derived parameters such as insulin secretion, insulin resistance, and early- and late-phase insulin secretion in the male T2DM subjects(p <0.05), but not in the non-diabetic and female T2DM subjects. The relationship between PFC and OGTTderived parameters was also more obvious than that for LFC in overweight and obese male patients with T2DM whose BMI was >24 kg/m2. Conclusion. PFC and LFC were both associated with β-cell dysfunction and insulin resistance in males with T2DM. The relationship between PFC and β-cell dysfunction and insulin resistance was more obvious than that observed for LFC in overweight and obese male T2DM patients. More attention should therefore be paid to PFC in clinical settings.

Context. Regulatory T cells (Tregs) have critical roles in preventing autoimmune diseases such as Hashimoto’s thyroiditis (HT). Forkhead box P3 (Foxp3), the master transcription factor of Tregs, plays a pivotal role in Treg function. Objective. Herein, we investigated the association of two single nucleotide polymorphisms (SNPs) of the Foxp3 gene with HT development. Methods and study design. A total of 129 HT patients and 127 healthy subjects were genotyped for rs3761548 (-3279 A/C) and rs3761549 (-2383 C/T) in the Foxp3 gene, using polymerase chain reaction-restriction fragment length polymorphism. Results. Genotypic and allelic distribution of rs3761548 SNP showed a significant association with HT. The CC genotype was observed in 37.2% of patients versus 22.1% of the controls [P<0.008, odds ratio (OR): 2.1; 95% confidence interval (CI): 1.2-3.6] and the AC genotype in 41.1% of patients compared to 54.3% of the controls (P<0.025, OR: 2.1; CI: 1.2-3.6). In addition, higher frequency of C allele in patients compared to controls (P=0.05, OR: 1.4; 95% CI: 0.9-2) suggested that patients with the CC genotype and C allele had increased susceptibility to HT. There were significantly higher serum levels of anti-thyroid peroxidase (ATPO) antibody in patients with the rs3761548 CC genotype (1156±163 IU/mL) compared to the other genotypes (≈582-656 IU/mL; P<0.004). We observed a greater frequency of the AC genotype in patients who had decreased ATPO antibody levels (P=0.02). Conclusions. The association of the rs3761548 SNP with risk of HT and its influence on ATPO antibody levels suggested an important role for Foxp3 in the biology and pathogenesis of HT.

Introduction. Life threatening heart disorders secondary to paediatric and adolescent hyperthyroidism are exceptional.\r\nAim. We aimed to study cardiothyreosis frequency and outcome in children and adolescents with hyperthyroidism diagnosed between 1980 and 2010.\r\nMaterial and methods. In this retrospective study we observed 160 clinical and biological hyperthyroidisms in children (&#8804; 16 years) and adolescents (16-20 years).\r\nResults. Among them four girls aged 3, 16, 17 and 18, without previous familial history of heart diseases, had congestive heart failure (2.5%) without rhythmic troubles. Symptoms of cardiac insufficiency were resistant to digitalis and diuretics, but after anti thyroid drugs, there was an integral restitution of heart function in three\r\ncases and a persistent mitral, aortic and tricuspid regurgitation in one case arguing for heart rheumatic disease prior to hyperthyroidism.\r\nConclusion. Heart failure secondary to thyroid hormones excess is extremely rare before age of 20. Among 160 paediatric and adolescent hyperthyroidisms seen in 30\r\nyears, four girls had life threatening congestive cardiac insufficiency (2.5%), but after euthyroidism, heart insufficiency disappeared totally in all cases which\r\npleaded for a direct action of thyroid hormones excess on heart function.