ACTA ENDOCRINOLOGICA (BUC)

Objective. Thyroid dysfunction represents common disorder occurring very frequently among women of reproductive age, including pregnancy. The aim of this literature review was to determine in which way thyroid function during pregnancy is associated with GDM. Design. We conducted review of the literature following the basic principles of literature search. Methods. Two researcher independently searched PubMed in the period of last five years (2018-2023) to identify eligible studies regarding thyroid function and GDM. Results. From 51 papers initially found after the inserting key words in PubMed search field 30 were excluded after the title and abstract review. After reading full text of 21 articles, 15 were included in the review. Conclusions. Our review of literature showed not only that two most common disorders during pregnancy were GDM and thyroid dysfunction, but also indicated that they were in positive correlation.

Background. Hyperuricemia is associated with non-alcoholic fatty liver disease (NAFLD). Aim. We therefore aimed at evaluating the influence of allopurinol on the course of NAFLD in rats. Study Design. We divided 21 mature albino Sprague Dawley rats into three groups: controls (n = 7, normal diet for 12 weeks); NAFLD rat models (by feeding water containing 30% fructose for first 8 weeks) treated with allopurinol subsequently for the next 4 weeks (n = 7); and similar case treated with placebo (saline) subsequently for the next 4 weeks (n = 7). Methods. We compared the histopathological scores, IL-1 and IL-2 immunoexpression levels across the groups. Liver histopathological score was determined by observing the steatosis (the percentage of liver cells containing fat): <25% = 1+, 25% - 50% = 2+, 51% - 75% = 3+, >75% = 4+; inflammation and necrosis: 1 focus per low-power field = 1+; and 2 or more foci = 2+. The number of liver IL-1 and IL-2 positive cells was measured by systematically scoring at least 100 hepatocyte cells per field in 10 fields of tissue sections by a magnification of 100. Results. Xanthine oxidase (XO) activity and lipid peroxidation was significantly different in the allopurinol group compared to the saline group (XO; 0.098 ± 0.006 mU/mg vs. 0.162 ± 0.008 mU/mg, p = 0.01, 0.116 ± 0.040 nmol malondialdehyde/mg versus 0.246 ± 0.040 nmol malondialdehyde /mg, p = 0.01). The allopurinol group had lower histopathological scores, IL-1 and IL-2 immunoexpression levels in the liver compared to the saline group (2.13 ± 0.35 against 5.45 ± 0.24, p = 0.003, IL-1; 5.76 ± 0.43 against 12.85 ± 3.26, p = 0.023, IL-2; 8.55 ± 1.14 against 56.23 ± 7.12, p = 0.002). Conclusions. Allopurinol has a therapeutic role against the progression of NAFLD of the rats.

Introduction. KCNJ11 gene activating mutations play a major role in the development of neonatal diabetes mellitus (NDM). KCNJ 11 gene encodes the Kir 6.2 subunit of ATP- sensitive potassium channel which is a critical regulator of pancreatic beta-cell insulin secretion. Aim. To study KCNJ11 gene mutations in infants with NDM and the effect of sulfonylurea treatment on the glycemic control in patients with KCNJ11 gene mutation. Subjects and methods. Thirty infants with NDM were screened for KCNJ11 gene mutations by DNA sequencing, insulin therapy was replaced by sulfonylurea treatment in patients with mutations. Results. R201C heterozygous mutation was found in one patient who was successfully shifted from insulin therapy to sulfonylurea treatment, while E23k, I337V, and S385C polymorphisms were detected in 14 patients. Conclusion. Screening for KCNJ 11 gene mutations could lead to identification of patients with mutations who can be successfully shifted from insulin therapy to sulfonylurea treatment improving their quality of life.

Objective. Endoplasmic reticulum stress (ERS) is suspected as an important factor in the initiation of insulin resistance. Aim. To explore the effects of exendin-4 (Ex- 4) on the endoplasmic reticulum stress (ERS)-mediated insulin resistance in 3T3-L1 adipocytes. In our study, 3T3-L1 adipocytes were pre-treated with ERS inhibitors tauroursodeoxycholic acid (TUDCA), Ex-4 and an ERS inducer tunicamycin (TM) then induced insulin resistance. Glucose consumption of the adipocytes was measured. Western blots determined the protein levels of ERS markers and insulin signaling pathway. Results. TM treatment reduced insulin-stimulated glucose consumption by 19.7% in 3T3-L1 adipocytes. This repression was blunted by 24h pre-treatment with TUDCA or Ex-4. Ex-4 augmented insulin-stimulated glucose consumption in adipocytes by 14.9%. Western blotting showed that TM treatment significantly increased the ER stress markers including p-IRE, p-JNK, p-PERK, p-eIF2a and ATF6 expression, whereas 24h pre-treatment of adipocytes with TUDCA or Ex-4 alleviated the ER stress. Ex-4 alleviates ERS-induced insulin resistance by upregulating the expression of phosphorylated Akt. Conclusion. ERs mediates insulin resistance in 3T3-L1 adipocytes, and exendin-4 significantly improves this insulin resistance.

Background. Chronic inflammation is associated with different cancers, and is identified as a key pathogenic mechanism in ovarian cancer. The purpose of our study was to evaluate systemic inflammation markers, as predictive and prognostic factors, in ovarian cancer patients with initial surgical treatment. Subjects and Methods. We performed a retrospective study on 60 ovarian cancer patients with primary cytoreduction surgery, between 2010-2018, with a follow-up period of at least one year. We analyzed systemic inflammation markers and their correlations with the clinical, paraclinical, tumor characteristics, or treatment particularities, and evaluated them as prognostic factors for overall survival. Results. In the univariate analysis, no statistically significantly differences were observed, by correlating the systemic inflammation markers with age, reproductive status, FIGO stage, or type of cytoreduction. Higher neutrophillymphocyte ratio (NLR) and platelet-lymphocyte ratio (PLR) were statistically significant associated with deceased patients, and lower lymphocyte-monocyte ratio (LMR) had statistical significance for living patients. For the patients in the group, the increase of NLR, as well as of PLR leads to the increased risk of death, and the increase of LMR leads to the decrease of this risk. In the multivariate regression analysis, the increase of NLR determined an increased risk of death by 9.7%, and for LMR a reduced risk of death by 46.9%. Conclusions. Systemic inflammation markers had no statistical significance correlated with age, reproductive status, FIGO stage, serous cancer type, or type of cytoreduction but only with overall survival. NLR is an independent risk factor, while LMR is an independent protection factor as well as optimal cytoreduction.

Context. Hashimoto’s thyroiditis is the most common autoimmune disorder as cause of secondary hypothyroidism. The disease is associated with several metabolic disturbances and inflammatory disorders. Objectives. The aim of the current report was to evaluate several inflammatory and metabolic predictors of Hashimoto’s thyroiditis. Subjects and Methods. In the current study, forty patients with Hashimoto’s thyroiditis participated in the current study. They were aged between 20 to 50 years old. Anthropometric and nutritional measurements were assessed and biochemical factors including serum VEGF, IL-23, Nesfatin-1 and serum lipids were measured. Results. Waist circumference was higher among patients with lower serum TSH concentrations. Serum HDL and T4 concentrations were lower and serum IL-23 was higher among patients with higher TSH concentrations. BMI, WC and serum HDL were negative predictors of serum TSH while IL-23 was positively associated with TSH concentrations. Serum lipids including TC, TG and LDL were also negatively associated with T3 and T4 concentrations. Conclusions. According to our findings, VEGF and serum IL-23 were potent predictors of Hashimoto’s thyroiditis. However, further studies are warranted to better clarify these associations and underlying pathologic mechanisms.

Background. In the Carpathian area of Romania the Iodine Deficiency Disorders (IDD) including endemic goiter are a public health problem. Recently, the legislation imposing salt iodization was strengthened (from 10 to 20 ± 5 mg iodine/kg salt) and enlarged (universal salt iodization, USI, has been applied to bread industry since 2002). Objective. The effect of bread iodization by law upon the characteristics of goiter endemy was assessed in Arges county, Romania. Design. The characteristics of goiter endemy (as defined by WHO/ICCIDD/UNICEF) were determined in children in the years 1999 (control group C) and 2004 (study group S), two years after universal bread iodization. In the control group C there were 1,241 schoolchildren 6-14 years old, living in 5 villages and in Pitesti town. In the study group S there were 408 schoolchildren 6-12 years old, living in 7 villages and in Pitesti town. After universal bread iodization, a neonatal screening for hypothyroidism was also performed on 11,216 newborns in Arges county, between January 2003 and December 2004. The content of KIO3 in the salt was assessed both in samples collected from village shops in the years 1999 (10 samples) and 2004 (17 samples). The iodine content of drinking water in Arges county villages was assessed in 1999. Methods. Three parameters of IDD endemy were evaluated, i.e. the thyroid volume in schoolchildren by palpation or/and ultrasonography, urinary iodine by the Sandell-Kolthoff method, and neonatal blood TSH levels in dry spot by immunoassay. A questionnaire was filled in by 912 schoolchildren in 1999 and by 408 schoolchildren in 2004.

Context. In the year 2003-2004 a circumstantial investigation of young men reproductive health parameters was performed in Nordic and Baltic countries, but sexuality remained undetermined. Objective. To determine the suitability of the European Male Ageing Study – Sexual Function Questionnaire (EMAS – SFQ) for investigation of sexuality of 26–36 year aged general population and to investigate sexuality of Kaunas participants in the project “The reproductive function of Estonian, Latvian and Lithuanian Young men (2003-2004)” (KELLY), using EMAS – SFQ. Design. Sixty one 26–36 year aged KELLY men were recaptured from the list of participants in a 2003-2004 study and completed EMAS – SFQ. Their anthropometric characteristics, scores of sexuality (22 parameters from EMAS – SFQ, 3 calculated parameters and 2 parameters consisting from answers to the only question - masturbation and erectile function-for each participant) were analysed, in conjunction with anthropometric, sperm quality and hormone levels of 2003-2004 18–25 year old general population. Results. Overall sexual functioning and masturbation were higher as compared to all the published data for different age men and different testosterone concentration groups of EMAS study. Conclusions. KELLY sexuality results, obtained using EMAS – SFQ, would be considered as referral values for young men in countries with generally good reproductive health.

Objective. Medical Nutrition Therapy (MNT) is important in the treatment and regulation of diabetic patients. In this study, it was aimed to evaluate the effects of medical nutrition therapy on Pentraxin-3, hsCRP and body composition analysis in Type 2 diabetes patients (DM). Methods. This study included 160 individuals who were admitted and diagnosed with Type 2 DM. Laboratory, clinical, anthropometric and body composition parameters were obtained 3 months after baseline evaluation of the patients and the MNT was given by the dietitian. Results. After 3 months MNT, weight, body mass index, waist circumference, body fat weight, body fat ratio and visceral fat area (p<0.001), glucose (p<0.001), insulin (p=0.033), HOMA index (p=0.004), HbA1c (p<0.001), total cholesterol (p=0.001), LDL (p=0.008), ALT (p<0.001) and hsCRP (p<0.001) levels were significantly lower than they were before MNT. There wasn’t significant difference in triglyceride (p=0.509), HDL (p=0.079), Pentraxin-3 (p=0.706) levels and waist-to-hip ratio (p=0.802). The level of Framingham risk score after MNT was significantly lower (p<0.001). Conclusion. In this study, it was cocluded that MNT, applied to patients with Type 2 DM decreased cardiovascular risk and inflammation, contributed to the maintenance of glycemic control, and a significantly improved the body composition.

Background. Osteoporosis has a high incidence after menopause, and at the same time the relationship between menopausal oestrogen deprivation and proinflammatory status is considered to be involved in postmenopausal bone turnover. Objective. The aim of this study was to evaluate the serum levels of IL-1β and of the TNFα in pre and postmenopausal women, as well as to investigate the relationship between these cytokines and bone mineral density. Design. A case-control study was performed during a period of 12 months. Subjects and Methods. The study included 150 women divided into 4 study groups. Serum levels of IL-1β and TNFα were determined using multiplex cytokine kits. BMD was measured by DXA at the level of the hip and lumbar spine. Results. Serum concentration of IL-1β is significantly higher in natural and surgically induced menopausal women, compared to women in the control group. Serum levels of TNFα in postmenopausal women and with surgically induced menopause are significantly higher than in fertile and premenopausal women. Serum levels of IL-1β are significantly higher in patients with osteopenia and osteoporosis compared to patients with normal BMD values. We found a negative correlation between serum levels of IL-1β, TNFα and BMD in pre and postmenopausal women, and in women with surgically induced menopause. Conclusions. Serum levels of IL- 1β and TNFα are significantly higher in menopausal women compared to fertile women. IL-1β is significantly higher in patients with osteopenia and osteoporosis than in women with normal BMD values, and IL-1β and TNFα associate negatively with BMD in pre and postmenopausal women, as well as in women with surgically induced menopause.