ACTA ENDOCRINOLOGICA (BUC)

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.

Context. Endometriosis is a common gynecological disease, characterized by ectopic deposits of endometrial tissue outside of the uterine cavity, and it is associated with pelvic pain and infertility, with an important impact on the quality of life. At this point there is a controversy regarding the etiology and pathophysiology of endometriosis and it seems that pro-angiogenic growth factors might be involved, but their role is not completely understood. Objective. To evaluate the serum concentration of the main growth factors in patients with diagnosed endometriosis compared to healthy controls. S ubjects and Methods. A total of 157 women were divided into two study groups (Group I – endometriosis; Group 2 – healthy women). Serum levels of VEGF, G-CSF, GM-CSF, b-FGF, EGF, and HGF were measured with Human Multiplex Cytokine Panels. Results. VEGF serum levels were significantly lower in women with endometriosis compared to controls (1.924±0.145 compared to 1.806±0.078 pg/mL, p<0.001). Serum levels of GM-CSF, b-FGF, EGF, and HGF respectively did not differ significantly between patients with endometriosis and healthy controls. G-CSF had a very low detection rate. Conclusions. The present study showed that VEGF serum levels are significantly lower in endometriosis patients compared to healthy controls, indicating a possible role in endometriosis pathogenesis.

Introduction. Adiponectin, resistin and osteoprotegerin (OPG) are cytokines expressed in the adipose tissue. Pregnancy is associated with gradually increased maternal\r\nlevels of these molecules, also detected in significant amounts in umbilical cord blood serum samples.\r\nAim, patients and methods. To establish the relationships of maternal and umbilical adiponectin, resistin and OPG levels to both maternal and fetal anthropometric measurements and insulin sensitivity, 28 mother-newborn pairs were enrolled in the study. Blood samples were collected in a fasting state, after delivery, and serum insulin, C-peptide, sex hormone-binding globulin, adipocytokines, OPG and bone specific alkaline phosphatase (BAP) were measured.\r\nResults. Compared to maternal values, umbilical serum adiponectin levels were about 3-fold higher; additionally, significantly higher resistin and lower OPG levels were\r\nobserved. Stratification of umbilical and maternal adiponectin levels according to tertiles of birth body weight demonstrated significantly lower maternal adiponectin\r\nlevels by tertiles of neonatal body weight. No relationships were noticed between infant birth weight and maternal or umbilical serum resistin and OPG, respectively. Umbilical resistin was significantly associated to both\r\nmaternal resistin and umbilical adiponectin. Multiple regression analysis showed that maternal BMI, umbilical insulin, C-peptide and resistin explained 71.83% of umbilical serum adiponectin variability. Umbilical resistin was independently predicted by umbilical adiponectin, umbilical C-peptide and maternal BMI, and the model explained 81.49% of umbilical resistin levels.\r\nConclusions. In human, umbilical serum adiponectin and resistin levels are significantly higher compared to adults. These adipokines may mediate the effects of maternal body mass on fetal development. The biology of the\r\nOPG/RANKL cytokine system in fetuses and newborns needs further research.

Endemic goiter occurred in different degrees throughout 2/3 of Romania, mainly in the Carpathian area. The prophylaxis of iodine deficiency disorders (IDD) using salt iodization was introduced in 1956 with potassium iodate, KIO3, 15-25 mg/1kg salt, but only in 23 districts. In 2002 a new legislation introduced the mandatory use of the iodized salt in a higher concentration in households of all 41 districts and also in the baking industry. The study aims to evaluate the effects of iodine legislation changes upon the urinary iodine excretion (UIC) in schoolchildren (study group A) and pregnant women (study group B). Urine samples were collected from 3737 schoolchildren aged 6-14 years of 14 districts and from 1283 pregnant women of 11 districts in the years 2004-2005. In two areas - Bistrita Nasaud and Bucharest - the number of schoolchildren was larger, i.e. 465 and 1617 respectively. UIC was determined in spot urine samples by Sandell Kolthoff?s method. The results show in schoolchildren an increase of the median UIC in 9 out of 14 districts up to 90 ? 61.1 ?g/L (range 12.5-300 ?g/L). Six of these districts are in the Carpathian area. However, in pregnant women in 2004, UIC still showed low levels of 55 ? 48.78 ?g/L (range 12.5-280 ?g/L) in all 11 studied districts and in Bucharest, close to the UIC obtained in the year 2001. In conclusion, this study revealed an increase of median values of UIC in schoolchildren after universal salt iodization program. The persistence of iodine deficiency in pregnant women in the studied districts is an emergency problem that has to be solved as soon as possible. This fact involves the necessity of a large monitoring program in the next years, in all districts in urban and rural areas and in all known pockets of endemia.

Background. The pathogenesis of pre-eclampsia involves inflammation, endothelial\r\ndysfunction and enhanced oxidative stress. Interleukin (IL)-6 is a major pro-inflammatory\r\ncytokine, while leptin is released in large amounts by the adipose tissue, but also by placenta.\r\nAim. The present study aims to evaluate total maternal serum leptin and IL-6 levels in\r\npre-eclampsia compared to normal pregnancy and non-pregnant status.\r\nMethods. We enrolled 65 women in a transversal study; pre-eclampsia was diagnosed\r\nin 25 (group 1), 25 women had a normal pregnancy (group 2), while in 15 pregnancy was\r\nexcluded. Groups were matched for chronological and gestational age and body mass index\r\n(BMI) accordingly. Total serum leptin and serum IL-6 were determined using ELISA, after\r\nan overnight fasting period of at least 12 hours.\r\nResults. Both leptin and IL-6 concentrations were significantly higher in women in the\r\nthird trimester of pregnancy developing pre-eclampsia compared to normotensive pregnant\r\nwomen (p=0.001). Normal pregnancy was characterized by increased serum leptin levels\r\n(p=0.001) as well as increased IL-6 levels (p=0.001) in comparison to non-pregnant status.\r\nIn women with pre-eclampsia, leptin was positively and significantly correlated with\r\ndiastolic blood pressure (r=0.45, p=0.02), proteinuria (r=0.48, p=0.01) and uric acid values\r\n(r=0.39, p=0.04) and inversely related to HDL cholesterol levels (r=-0.64, p=0.0001).\r\nLikewise, IL-6 was positively related to systolic and diastolic blood pressure (r=0.41,\r\np=0.008 and r=0.60, p=0.00003, respectively), proteinuria (r=0.38, p=0.01) and uric acid\r\nvalues (r=0.43, p=0.004). However, leptin had no correlation with pregnancy outcome in\r\nwomen with or without pre-eclampsia. In contrast, IL-6 was negatively correlated with both\r\nfetal birth at weight (r=-0.35, p=0.02) and Apgar score (r=-0.38, p=0.01).\r\nConclusions. In conclusion pre-eclampsia associates significantly increased serum\r\nleptin concentrations and IL-6 production compared to normal pregnancy. In contrast to\r\nleptin, IL-6 may predict pregnancy outcome (fetal birth weight and Apgar score) in women\r\nwith pre-eclampsia.

Context. The effects of COVID-19 on the adrenocortical system and its hormones are not well known. Objectives. We studied serum cortisol, serum adrenocorticotropic hormone (ACTH), and their ratio in hospitalized non-critically ill COVID-19 patients. Design. A prospective case-control study. Methods. The study participants were divided into 2 groups. Group 1 consisted of 74 COVID-19 patients. The second group consisted of 33 healthy persons. Early admission above hormones levels was determined and compared between the study groups. Besides that, COVID-19 patients were grouped according to their Glasgow Coma Score (GCS), CURB-65 score, and intensive care unit (ICU) requirement, and further sub-analyses were performed. Results. There were no significant differences in the mean age or gender distribution in both groups. In the patients’ group, the serum ACTH concentration was lower than in the healthy group (p<0.05). On the other hand, the serum cortisol levels and cortisol/ACTH ratio of the patients’ group were significantly higher than of the healthy controls (p<0.05, all). Further analyses showed that, although serum cortisol and ACTH levels were not high, the cortisol/ACTH ratio was higher in COVID-19 patients with low GCS (<15) than patients with normal GCS (=15) (p<0.05). In COVID-19 in patients with different CURB-65 scores, the cortisol/ACTH ratio was significantly different (p<0.05), while serum cortisol and ACTH were not different in groups (p>0.05). Serum cortisol levels and cortisol/ACTH ratio were higher but ACTH level was lower in the ICU needed COVID-19 patients than in patients who do not need ICU (p<0.05). Conclusion. Our pilot study results showed that the cortisol/ACTH ratio would be more useful than serum cortisol and/or ACTH levels alone in evaluating the adrenocortical system of COVID-19 patients. Still, further detailed studies are needed to confirm these.

Radioactive iodine (RAI) therapy is a mainstay adjuvant treatment for thyroid cancer. Administration of RAI therapy after total or near-total thyroidectomy has shown a survival advantage in numerous properly selected patients. However, the role of RAI therapy after reoperation for persistent or recurrent differentiated thyroid carcinomas (DTCs) is unclear. One reason may be the possible downregulation of the I- transport system after primary surgery. RAI is transported by the sodium iodide symporter (NIS), PENDRIN, anoctamin 1 (ANO1) and cystic fibrosis transmembrane conductance regulator (CFTR) and emits β particles that destroy follicular cells. The identification of pathways of iodide (I-) transport has allowed use of the transport system to render tumours susceptible to RAI treatment via gene therapy. This review focuses on the effect of RAI therapy in follicular cell-derived thyroid cancers and offers potential novel targets that enable improved radioiodine uptake and thus an improved prognosis of thyroid cancer.

Vertebrate nonapeptide neurohormones constitute an evolutionarily conserved family, involved in vital functions, such as hydro-osmotic balance regulation, reproduction and social behaviour. Two human members of this family are known, vasopressin (AVP) and oxytocin (OXT), with their highly homologous genes closely located on Chr 20p13. Presence of vasotocin (AVT) in man has been suggested, but remains controversial, and genetic evidence is lacking. AVT activity could be explained by the presence of a third distinct gene for AVT or an RNA-processing mechanism involving products of AVP and/or OXT genes. To test the first hypothesis, we developed bioinformatics and experimental approaches using genomic DNA and fetal tissues mRNAs. Family-specific primers for AVT and neurophysin were designed based on CODEHOP strategy and used in our experiments. Results of bioinformatics and genomic DNA experiments (family-specific and Alu step-out PCR) suggest there is no evidence for an AVT gene in the genome. RNA-based techniques 3?-RACE and Family-Specific Domain Restriction Fragment RTPCR provided evidence for new transcript species that could code for AVT. Further experiments will be needed to characterize them. We discuss potential mechanisms of AVT mRNA generation based on AVP and OXT mRNAs, by alternative splicing, heterologous transsplicing or RNA-editing. While all methods we developed proved feasible, current results suggest there is no AVT gene in the genome, but specific mRNAs could be present in fetal tissues. Their full characterization may potentially allow identification of vasotocin mRNA and shed light on a subject of fundamental scientific interest.

Objectives. The aim of this study was to evaluate serum levels of interleukin (IL)-8 in pre- and postmenopausal women and in patients with surgically-induced menopause, and the relationship between IL-8 and vasomotor symptoms. Material and Method. 175 women were enrolled and were divided into 5 groups (I – Fertile women; II – Pre- and perimenopausal women; III – Postmenopausal women; IV – Surgically-induced menopause; V – Chronic inflammation). Multiplex cytokine kits were used to evaluate serum levels of interleukin-8. We determined the serum levels of the follicle stimulating hormone, of the luteinizing hormone, 17β-estradiol, progesterone, dehydroepiandrosterone and dehydroepiandrosterone sulfate using sandwich ELISA. The severity of the vasomotor symptoms was evaluated according to FDA guidelines. Results. Serum concentration of IL-8 in women with natural menopause (233.0±226.5 pg/ml; p<0.001) and in women with surgically-induced menopause (148.0±162.0 pg/ml; p=0.045) is significantly higher than in women of reproductive age (84.88±82.32 pg/ml). Serum levels of IL-8 in premenopausal women, postmenopausal women, and in women with surgically-induced menopause, respectively, with severe and moderate hot flashes, on one hand (174.8±90.94 pg/ml, 369.3±194.2 pg/ml, respectively 274.1±146.3 pg/ml), is significantly higher than in women without vasomotor symptoms or with mild hot flashes, on the other hand (19.97±22.15 pg/ml, 28.66±35.72 pg/ml, respectively 28.94±37.68 pg/ml; p<0.001). Serum levels of IL-8 are significantly higher in women of reproductive age with chronic inflammatory pathology (152.3±121.0 pg/ml) than in women without such pathology (84.88±82.32 pg/ml; p=0.02). Conclusions. IL-8 is significantly higher in postmenopausal women with vasomotor symptoms than in women without vasomotor symptoms. In the postmenopausal group, the serum levels of IL-8 are similar to those in women with chronic inflammatory pathology. IL-8 could be a key factor in occurrence of hot flashes in menopause and could be associated with peripheral vasodilatation in these women.

Purpose. To determine the effectiveness of the basal calcitonin (CTb) determination in the early postoperative period to predict the possible recurrence (persistence) of medullary thyroid cancer (MTC). Material and Methods. A retrospective study of the treatment results in 194 patients with MTC (148 (76.3%) primary – group 1 and 46 (23.8%) recurrent – group 2) according to the levels of CTb in the first week after surgery and one year later. All groups were analyzed by staging, the level of preoperative and postoperative basal calcitonin 5 days and 1 year after the primary surgery. Findings. Among all patients, women prevailed – 144 (74.2%), the average age was (48.7±15.2), the average follow-up period was 67.5 months. Basal calcitonin was studied in patients of all groups in the preoperative and serially in the postoperative periods: 5 days and 1 year after the most radical surgical volumes. To test the hypothesis about the possibility of using CTb indicators in the early postoperative period, the degree of compliance with normal calcitonin indicators (≤18 pg/mL) was assessed by observation groups 5 days and 1 year after surgery. Conclusions. 1. The CTb value 5 days after surgery is no less a reliable marker of the result of surgical treatment of MTC than the currently recommended CTb measurement 2-3 months after surgery. 2. The technique is applicable for both primary and reoperations used for recurrent forms of medullary thyroid cancer.