ACTA ENDOCRINOLOGICA (BUC)

Background. Autoimmune thyroid diseases (AITD) including Graves’ disease (GD) and Hashimoto’s thyroiditis (HT) are complex genetic diseases. TSHR is considered as candidate gene in GD. This finding prompted us to investigate the association of TSHR gene polymorphism with the risk and the prognosis of AITD in Tunisia. Methods. A total of 84 healthy controls and 91 patients with AITD (69HT and 22 GD) were genotyped for TSHR rs74067403A>G polymorphism and 134 healthy controls and 149 patients with AITD (98 HT and 51 GD) were genotyped for TSHR rs1054708 T>C polymorphism. Results. For rs1054708, we found an association between HT, AITD and the heterozygous genotype TC, the mutated genotype CC and the genotypes presented the mutated allele C (TC+CC) and with mutated allele C. The heterozygous genotype TC and the genotypes that presented the mutated allele C of rs1054708 are associated with male patients with AITD evenly the heterozygous genotype TC is associated with age of onset of disease. Conclusions. These preliminary results suggest that TSHR rs1054708 polymorphism may be a protective factor against HT and AITD. This polymorphism can affect the etiology of AITD between men and women and also by age.

Introduction. With the introduction of iodized salt, more and more people are exposed to iodine sufficiency in some regions. The purpose of this study was to investigate the prevalence of nontoxic nodular goiter (NTNG) in the littoral region with high iodine supply after a nearly twodecade universal salt iodization. Subjects and Methods. Eight hundred and thirtyfive participants (from 25~65 years; males 421 and females 414) were invited for the study from Huan-cui District of Weihai City, Shandong Province from January 2013 to September 2014. All participants were inspected and diagnosed by endocrinologists according to the thyroid function tests and the thyroid gland imaging. After the normal diet of three days, the urine samples of the participants were collected between 8:00AM and 9:00AM and the urinary iodine (UI) concentrations were analyzed using Urinary Iodide Test Kit. Results. The overall prevalence of NTNG in the region was 40.1%, and different prevalence occurred in the different age ranges (p<0.01). The prevalence of NTNG was 32.51%, 37.44%, 49.70%, 58.57 and 74.77% in the age group of ≤ 30, 31-40, 41-50, 51-60 and >60 years, respectively. Meanwhile, the prevalence of NTNG in women (42.08%) was higher than that in men (34.29%, p<0.05). The median of UI concentrations were 139.4μg/L and 101.5μg/L for the group with NTNG and without NTNG, respectively (p<0.01). However, there was no significant difference in UI concentrations among the groups with different age ranges (p>0.05), and statistical difference was not observed for UI concentrations between women and men (p>0.05). Intriguingly, higher UI concentrations were found in the group with larger thyroid size (p<0.01). Conclusion. The iodine excess can lead to the high occurrence of nodular goiter in the littoral region, and individual UI concentration detection is recommended for the iodine nutritional status analysis among normal people when Universal Salt Iodization (USI) continues to be implemented in the region.

Context. To analyze the dynamic changes of serum thyrotrophin receptor antibody (TRAb) and thyroid peroxidase antibody (TPOAb) in Graves’ disease (GD) patients before and after radioactive iodine (RAI) treatment and to investigate if TRAb and TPOAb play a role in the occurrence of early hypothyroidism after 131I therapy for Graves’ hyperthyroidism. Subjects and Methods. A total of 240 patients newly diagnosed with GD were selected to study. A clinical and laboratory assessment was performed before and at 3, 6, and 12 months after 131I therapy. Chemiluminescent immunoassays were used to detect serum free triiodothyronine (FT3), free thyroxine (FT4), sensitive thyroid-stimulating hormone (TSH) and TPOAb concentration. Radio-receptor assay was used to measure serum TRAb concentration. According to the early onset of hypothyroidism in a year after RAI therapy, patients were divided into early hypothyroidism group (group A) and non-early hypothyroidism group (group B). Results. In both groups, serum TRAb and TPOAb increased at 3 months, reached the highest level at 6 months and returned to the baseline at 12 months after RAI therapy. TRAb showed a significant difference between the two groups at 6 months (P<0.01). Serum TPOAb in group A was higher than that in group B before and at 3, 6, 12 months after RAI therapy (P<0.05). Conclusions. Serum TRAb and TPOAb are closely related to the occurrence of the early hypothyroidism, and play an important role in judging prognosis after 131I treatment in Graves’ disease.

Background. Thyroid hormone participates in lipid metabolism regulation. However, the effects on triacyleride or triacylglycerol metabolism are complex and not fully clarified yet. In this study, we try to identify novel thyroid hormone-targeting lipogenic metabolic genes and analyze their molecular regulative mechanism. Method. Thirty-five promoters of twenty-nine human lipogenic regulative enzyme genes were constructed into pXP1 luciferase reporter plasmid (PFK2/FBP2-luc) and transfected into HeGP2 cells, respectively. Gene expression induced by triiodothyronine (T3) was detected by luciferase assay. The T3-activated gene promoter was then analyzed by sequence analysis, deletion and mutation, and electrophoretic mobility shift assay (EMSA). Results. After 10 nM T3 stimulation for 36 h, phosphogluconate dehydrogenase, malic enzyme, Glycerol- 3-phosphate acyltransferase (GPAT) 3, and 1-acylglycerol-3- phosphate O-acyltransferase (AGPAT) 2 were significantly activated, respectively. A AGGTCA-like-direct-repeat-4 consensus thyroid hormone response element (DR4-TRE)- like sequence was found in the GPAT3 promoter, which was then verified to be necessary for T3-induced GPAT3 activation by gene deletion and mutation analysis. EMSA further identified that T3-thyroid receptor (TR) α-retinoid-X receptor (RXR) complex directly bound on the GPAT3 promoter. Conclusion. Triiodothyronine could activate the GPAT3 through DR4-TRE-like sequence binding to participate in lipogenic regulation. AGPAT2 may be another thyroid hormone target enzyme.

In response to increasing interest of the European Commission on large-scale\r\ngenotyping for complex diseases, including variability in ethnic minorities in\r\nEurope (HEALTH-2009-4.3.3-1), at the end of 2008 we composed the\r\nHAPLOGENDIS consortium with partners from Russia and European countries. A\r\nfirst program (SICA) was proposed in cooperation with Russian Federal Agency for\r\nScience and Innovation, focusing on comparative population genetics on diseases\r\naccompanied by insulin resistance. Beside the specificity in analyzing the human\r\ngenome with SNP (single nucleotide polymorphism) and defining haplotype\r\nstructure of genes, the program rises new hypotheses which directly link\r\ncolonization of Europe at the Neolithic period from Eastern Ukraine or Anatolia\r\nwith the development of agriculture and major dietary and life style changes that\r\nmay have an impact on the genome. Although there will be many occasions to\r\nreview both genetic and clinical detailed aspects, this short note will expose some\r\nunifying ideas that joint these partners.

Background. This study aimed to assess the mechanism through which Wnt/ beta - catenin signaling pathway, and StarD7, prometes testosterone synthesis, and to explore a new pathway for the regulation of testosterone synthesis. Animals and Methods. Leydig cells were isolated from male Sprague-Dawley rats divided into four groups and treated with Annexin 5 in concentration of 0, 0.1, 1 and 10 nmol/L. Testosterone secretion, expression of StarD7, StarD7 mRNA, β-catenin and changes of β – catenin localization in Leydig cells of testis of rats were tested in the four groups. Results. mRNA and protein levels of StarD7 and β-catenin increased significantly, upon stimulation with 1 nmol/L annexin 5. Accumulation of β-catenin inside the cells and the nucleus, was observed by immunofluorescence staining, in cells treated with annexin 5. These findings indicate a possible role of StarD7 and β-catenin in the process of annexin5-mediated stimulation of testosterone synthesis. Conclusions. Wnt/β-catenin signaling pathway and StarD7 are involved in the process of annexin5 stimulation of testosterone synthesis. Activation of Wnt/ β-catenin signaling pathway by Annexin5, and increase in StarD7 expression lead to elevated expression of key regulatory enzymes in testosterone synthesis, thus promoting testosterone synthesis.

Objective. To observe the effect of adiponectin on osteogenesis in type 2 diabetic rats. Methods. The 4th-week-old male SD rats were divided into normal control group (n=18) and diabetic model group (n = 42). Type 2 diabetes was induced by high-fat and high-sugar diet and intraperitoneal injection of a low dose of streptozotocin (STZ). The successfully-induced diabetic rats were divided into diabetic group (DM=18) and adiponectin intervention group (APN=18). APN group was injected with APN 10 μg/kg*d. The rats were separately sacrificed at the 4th, 8th and 12th week after the intervention. Bone microstructure and adipose tissue were observed via HE staining. Bone marrow was extracted from one side of the femur, and the supernatant was achieved by centrifugation. After BMD assessed by DXA, the other side of the femur was for further HE staining. Runx-2 expression in the bone marrow cells was detected by RT-PCR. BALP and AOPPs in bone marrow supernatant were assayed by ELISA. AGEs were detected by immunohistochemical staining. Results. With the feeding time over, blood glucose, AOPP, and AGEs were increased, and Runx-2 mRNA, BALP, BMD were decreased in diabetic rat group(P<0.05). Oxidative stress (OS) maker (AOPP) was decreased and osteogenesis makers (Runx2 mRNA, BALP) were increased after intervention with exogenous adiponectin (P<0.05). At the 8th and 12th week, the trabecular bone became thinner and broken, and the fat cell number increased in all 3 groups, especially in the DM group. The adiponectin intervention group showed that the trabecular bone structure was moderately restored. Conclusions. OS is obvious in bone microenvironment in diabetic rats. OS may have an inhibitory effect on regulation of osteogenic differentiation factor Runx2, causing down regulation of osteoblast differentiation and bone formation. Adiponectin may improve OS response and protect the bone structure.

Background. Plasma level of ghrelin is possibly reduced in Helicobacter pylori infection and may account for the resultant failure to thrive. Objective. To investigate relationships between Helicobacter pylori infection, and plasma level of ghrelin, anthropometric measurements, appetite, educational and economical status of parents. Methods. Ninety-four children were screened for Helicobacter pylori infection with C-14 urea breath test. Anthropometric measurements were performed in Helicobacter pylori (+) and (-) groups. Plasma ghrelin was measured. Parents were asked to fill out the questionnaire prepared by the researcher on the number of family members, parents’ level of education, monthly income and children’s status for appetite. Results. Plasma ghrelin was lower in Helicobacter pylori (+) group (20.00 ± 22.10 ng/mL), compared to Helicobacter pylori (-) group (79.72 ± 78.13 ng/mL). The percentiles of measurements for height, weight and body mass index were higher in Helicobacter pylori (-) group. Results of C-14 urea breath test were negatively correlated with height, weight and body mass index; however, no correlation was detected between the results of C-14 urea breath test, and plasma ghrelin, number of family members, levels of parents’ education and income. A negative correlation was observed between the results of C-14 urea breath test and appetite. Conclusions. Helicobacter pylori infection is considered to play a restricting role in growth potential by decreasing ghrelin level in children. Moreover, the existence of a negative correlation between the results of C-14 UBT, and weight, height and body mass index suggests a possible link between Helicobacter pylori infection and poor growth.

Objective. This research aim was to evaluates the role of the pre-ablation neutrophil-to-lymphocyte ratio (NLR) and lymphocyte-to-monocyte ratio (LMR) as predictors of distant metastases in patients with differentiated thyroid cancer (DTC). Methods. A retrospective analysis was given to 140 patients with DTC who received 131I remnant ablation after surgery. The patients were divided into two groups based on the existence of distant metastasis. Results. The two groups showed no significant difference in age, gender, WBCs, neutrophils, monocytes, eosinophils, basophils and whether the tumor was multifocal. In the univariate analysis, significant differences were found in tumor size (p=0.021), lymphocyte (p=0.012), NLR (p=0.027), and LMR (p=0.007). According to the ROC curves, NLR had an AUC of 0.612 ± 0.097 with a cut-off value of 1.845, sensitivity of 60.0%, and specificity of 66.2% (p=0.027). LMR had an AUC of 0.638 ± 0.095 with a cutoff value of 4.630, sensitivity of 84.6%, and specificity of 35.4% (p=0.007). In the multivariate analysis, larger tumor size (OR=5.246, 95% CI 1.269-10.907, p=0.009) and higher NLR (OR=2.087, 95% CI 0.977-4.459, p=0.034) were statistically significant for distant metastases. Conclusion. This research reveals that pre-ablation NLR and tumor size are significantly statistically correlated with distant metastases in patients with DTC.

Hematopoietic stem cell transplantation (HSCT) is an effective treatment for various types of hereditary hematologic disease, hematological malignancy, primary immunodeficiency and metabolic disease. Thyroid dysfunction is a common complication of HSCT, which situation is mainly manifested as hypothyroidism and rarely as hyperthyroidism. This report presents a 28-yearold man who developed hyperthyroidism 9 years after sibling allogeneic HSCT, which was most likely caused by chronic GVHD. In the meantime, the patient also suffered from liver dysfunction and pancytopenia, for which he was inappropriate to take antithyroid drugs (ATD) for treatment of hyperthyroidism. The patient was orally administered 259 MBq 131I, an individualized dose. The symptoms of hyperthyroidism were mitigated by 131I treatment.