ACTA ENDOCRINOLOGICA (BUC)

The aim of this review is to indicate the current position on the role of thyroxine (T4) and fetal brain development with particular relevance to the human situation. Adequate maternal iodine nutrition and maternal circulating thyroxine (T4) concentrations are essential to ensure optimum T4 placental passage which in turn will ensure transport of T4 into fetal brain cells. These processes are discussed and the role of thyroid hormone transporters is considered. The emphasis on isolated maternal hypothyroxinaemia (IH) as an important factor affecting brain development is discussed from the animal experimental point of view as well as in the clinical setting. There is evidence of neurocognitive impairment as assessed by different modalities in children up to the age of 8 years and some suggestion of increased psychiatric disorder in older persons whose mothers had IH during gestation. Although international guidelines have not in general recommended thyroxine therapy for IH the recent demonstration of adverse obstetric outcomes in women with isolated maternal hypothyroxinaemia may warrant a revision of this strategy.

Over the last decades aging has become a major concern for both medical professionals and policy makers. European Commission has been launching a series of initiatives aimed at drawing attention to great social, political and economic importance of aging research and at finding as well as disseminating the best practices in order to attain a very important objective: to add two years of healthy live to people in Europe by 2020. Nevertheless, there is still controversy regarding the accepted age limit for older people and also concerning various aspects of aging and aging research, most important being the difficulty of correlating chronological age to biological age. A new perspective is suggested and this might help scientists and clinicians understand better the problems of old age and could facilitate targeting research and medical strategies to the most appropriate goals. Several very important projects in the field of aging, funded by European Commission, are presented and a novel approach to the specific situation of older people is offered.

Purpose. To re-examine our clinical practice and review strategy for treatment of primary hyperparathyroidism in patients with multigland disease. Methods. Retrospective analysis of 121 consecutive primary hyperparathyroidism (PHPT) patients who underwent surgery in a tertiary center between January 2010 and December 2014. Results. Of 121 patients with PHPT 87% had single gland adenoma (SGD) and 13% had multigland disease (MGD). The overall cure rate was 95.86%. MGD was more frequent in younger persons (<40y)(50% vs. 13.2%). All patients had SPECT-CT (Single Proton Emission Computerized Tomography) with 28% being SPECT-CT negative. Patients with MGD had a higher rate of persistent disease (13.33% vs. 2.83%). Specimen weight was <600mg in 75% of MGD patients. 67% of SPECT-CT negative patients had mild hypercalcemia (Calcium <2.75 mmol/L) which was more frequent in MGD patients (43% vs. 19%). Conclusions. MGD patients were more likely SPECT-CT negative (40% vs. 25.4%) and benefit from bilateral neck exploration (BNE) (74%). However, most SPECT-CT negative patients still have a single adenoma. In our series MGD was more frequent in younger patients, more likely SPECT-CT negative, often associated with mild hypercalcemia and had a higher persistence rate than SGD. BNE is the operation of choice in young, SPECT-CT negative patients. If ultrasound parathyroids suggests a single large adenoma, minimally invasive parathyroidectomy with intraoperative PTH monitoring can be considered.

Purpose. Minimally invasive follicular thyroid carcinomas (MIFCs) are uncommon; literature offers limited guidance on their natural history and management. Starting January 2015 we measured circulating tumor cells (CTCs) in patients with MIFC (n=22) or benign thyroid tumors with follicular features (n=4). Methods. In a retrospective analysis, we assessed detectability of and serial changes in CTC, compared demographic/clinical differences between CTC-positive versus CTC-negative subgroups using Student’s t-test, and examined correlations between CTC status and serum thyroglobulin using Spearman’s test. CTCs were quantitated via immunomagnetic separation/microscopic inspection. Results. Thirteen patients (50%: 12/22 MIFC, 1/4 benign tumor) were initially CTC-positive; 3 remained CTC-positive in ≥1 subsequent measurement. CTC-positive patients had larger tumors and more frequent multifocality and vascular invasion versus CTC-negative patients (n=13). However, no tested variable differed significantly between the subgroups. After 17.2±10.5 months, neither subgroup showed evidence of disease. Significant correlation was absent (p ≥ 0.263) between CTC and Tg negativity (r = 0.243; n=13 evaluable) or initial CTC positivity and Tg positivity (r = -0.418; n=9 evaluable). Conclusions. In the studied settings, CTC measurement is feasible, has unclear clinical/outcome implications, but may provide different information versus thyroglobulin testing. Lengthier assessment is warranted in larger series.

Context. Thyroid eye disease (TED), an orbital inflammatory status, generally occurred in Graves’ disease. Objective. This study aimed to acquire further insight into molecular mechanisms of TED, especially several key involved genes and pathways. Design. The microarray dataset GSE58331 including expression data for orbital adipose tissue samples, isolated from TED patients and normal controls, was downloaded from a publicly accessible Gene Expression Omnibus database. Differentially expressed genes (DEGs) were identified from 23 adipose tissues of TED patients versus 20 samples from normal controls. Subjects and Methods. A protein-protein interaction network of DEGs was constructed by using Search Tool for the Retrieval of Interacting Genes and Cytoscape 3.6.0. Several hub genes/proteins were extracted from the proteinprotein interaction network based on connectivity degree. Furthermore, we used the iRegulon plugin of Cytoscape3.6.0 to predict the transcription factors (TFs). Results. A total of 678 DEGs (538 up- and 140 down-regulated genes) were identified in TED patients. Proopiomelanocortin (POMC), interleukin 2 (IL-2), G protein subunit gamma 3 (GNG3), CXC motif chemokine receptor 4 (CXCR4), toll like receptor 4 (TLR4), colony stimulating factor 1 receptor (CSF1R), lysophosphatidic acid receptor 3 (LPAR3), CXC motif chemokine ligand-8 (CXCL8), etc., were considered as the hub genes among the DEGs. There were 6 TFs predicted to be differentially expressed in regulating the DEGs related to TED. A total of 71 DEGs had been reported to be associated with TED in the Comparative Toxicogenomics Database. Conclusions. Through this analysis, we have identified plenty of potential biomarkers and pathways which may have an important role in the pathogenesis of TED. However, these findings require verification by more detailed future experimental studies.

effects of Ultrasonic Coagulation (UC), Bipolar Energy Sealing System (BESS), Intra Operative Nerve Monitoring (IONM) and surgical experience on the complications of thyroid surgery. Method. The data of 1627 patients who underwent thyroid surgery for various indications in our department between 2009 and 2018 were analyzed retrospectively and the effects of different technological devices on complications were investigated. Results. Transient recurrent laryngeal nerve (RLN) palsy was higher between 2009 and 2013, when IONM was not in routine use (p=0.029). There were no significant differences between two energy devices (UC and BESS) in terms of transient or permanent RLN palsy, bleeding, and transient or permanent hypocalcemia. Multivariate analysis showed that young age (0.006), female gender (0.016), surgery type (p<0.001), and lateral neck dissection (p=0.026) are independent risk factors for transient hypocalcemia. Conclusion. The results indicate that there is no superior hemostatic device. IONM and specific branching decrease transient RLN palsy. Female gender, young age, completion thyroidectomy, and lateral neck dissection were independent risk factors for the development of transient hypocalcemia.

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.

Background. The purpose of this study was to explore the influencing factors of serum uric acid (SUA) level and related gene polymorphisms in the healthy population. Methods. A total of 346 healthy individuals screened from different areas in Shenyang City and 195 patients with high SUA levels were included. Results. The levels of TC (total cholesterol), HDL-C (high-density lipoprotein cholesterol), LDL-C (lowdensity lipoprotein cholesterol), TG (triglycerides), GLU (blood glucose) ALT (alanine aminotransferase), TBA (total bile acid), TBIL (total bilirubin), CR (creatinine) and CYSC (Cystatin C) were statistically different between the healthy and hyperuricemia population (P<0.05). However, there was no statistical difference in the UA level between the two groups (P>0.05). After adjusting for UA, TC, HDL-C, LDL-C, GLU, TBIL and CYSC, the additive and recessive models of rs2231142 were statistically significant in females (P<0.05). For males, haplotypes of A-C-A-A-G-G, A-CG- C-G-G and A-T-G-A-A-G had significant difference between the healthy and hyperuricemia population (P<0.05). For females, the haplotypes of A-C-G-C-G-G and A-T-A-CA- T had significant differences (P<0.05). Conclusion. The distributions of SLC2A9 (solute carrier family 2 and facilitated glucose transporter member 9), ABCG2 (ATP-binding cassette G2), GCKR (glucokinase regulatory protein), KCNQ1, IGFIR (Insulin-like growth factor-I receptor) and VEGFR (Vascular Endothelial Growth Factor Receptor) were balanced in the population in Shenyang City. The haplotypes of A-C-A-A-G-G, A-CG- C-G-G and A-T-G-A-A-G were the influencing factors of high SUA in the population in Shenyang City.

Objectives. Despite extensive research on endometrial cancer (EC) and endometrial hyperplasia, there is still a gap in understanding the molecular mechanisms underlying their development and progression. The aim of this study was to investigate the expression levels of FOXO-1, P27Kip1, miR-27, and miR-186, and Akt1, Akt-P proteins in patients with EC and endometrial hyperplasia compared to control subjects. Subjects and methods. Samples of the endometrial tumor (n=30), normal (control) (n=30) and endometrial hyperplastic (n=30) tissue were obtained from patients referring to Arash and Imam Khomani hospitals, Tehran, Iran. Expression levels of genes and microRNAs were evaluated by qRT- PCR. Western blot analysis was applied for protein evaluation. The data were analyzed using t-test, Mann -Whitney U, Pearson correlation coefficient analysis, ANCOVA and ANOVA. Results. There was significant decrease in FOXO-1 in EC tissue compared to control tissue (p<0.05). Significant increase was observed in expression of miR-27 in patients with EC (p<0.001) and hyperplasia (p<0.01), whereas miR-186 expression level increased significantly only in patients with EC (p<0.05). P27Kip1 expression level did not significantly change in patients with EC and hyperplasia. There was a significant association between expression levels of miR-27 with FOXO-1 and P27Kip1 in patients with EC. Western blot analysis revealed higher endometrial AKT1-P protein levels in patients with EC and hyperplasia than control subjects (p<0.05). Conclusions. Our findings suggest that FOXO-1, miR-27, miR-186, and Akt1-P/Akt1 protein have the potential to serve as tissue biomarkers for early diagnosis, prognosis, and progression of EC in the human reproductive system.

Introduction. Induction of heme oxygenase (HO) gene expression can protect lungs from Hypoxic Pulmonary\r\nVasoconstriction (HPV). Furthermore, there is evidence that Rho-kinase (ROCK) may be involved in HPV. Studies are going on to detect the real mechanisms involved in the phenomenon. Ghrelin, a 28-amino-acid peptide, has been shown that it may protect lungs from HPV side effects. The aim of this study was to evaluate the effect of exogenous ghrelin on HO and ROCK isoforms gene expression during chronic hypoxia (CH).\r\nMaterial and Method.Twenty four adult male Wistar rats were divided randomly in three groups. Hypoxic rats with saline or ghrelin treatment were placed in a normobaric hypoxic chamber (O2 11%), for two weeks. Controls remained in room air. HO and ROCK isoforms gene expression was measured by Real-Time RT-PCR. Lung tissues were histologically processed and stained with hematoxylin-eosin for morphometric analysis.\r\nResults. Morphometric analysis showed that ghrelin reversed the hypoxia induced pulmonary artery wall thickness (P < 0.001). In hypoxic animals, the amount of HO-1 expression increased but there was suppression in HO-2 gene expression (P < 0.05). Both ROCK-1 and ROCK-2 gene expressions were diminished after two-week hypoxia. Ghrelin treatment reduced the overexpression of HO-1 (P < 0.05), but had noeffect on ROCK gene expression.\r\nConclusion. Ghrelin by decreasing the expression of HO-1 and HO-2 in hypoxic animals may be involved in an adaptation\r\nmechanism during CH. However, ghrelin did not change ROCK isoforms gene expression, thus it could not affect HPV in this way. Nevertheless, more studies are needed to justify the protective roles of ghrelin for HPV.