ACTA ENDOCRINOLOGICA (BUC)

Type 2 diabetes (T2D) increases the risk of coronary artery disease (CAD) in patients with type 2 diabetes compared with nondiabetic subjects. Several genetic variants are considered as risk factors for CAD, including those implicated in dyslipidaemia and oxidative stress. The PPARGC1A gene is considered as a key regulator of pathophysiological processes contributing to CAD. Aim. We investigated whether the Gly482Ser polymorphism (rs8192678) increased susceptibility to CAD in Iranian population and whether it was associated with clinical and metabolic parameters. Patients and methods. A total of 290 subjects including 149 CAD patients with a history of diabetes and 149 controls were included in our study. The Gly482Ser polymorphism was genotyped using ARMS-PCR method. Based on the type of variables, by the use of SPSS software (Statistical Package for Social Sciences Inc., Chicago, IL, USA) statistical analyses were performed. Results. We found a significant difference in the Gly482Ser substitution between the case and control subjects in Iranian population. However, no significant association was observed between Gly482Ser genotypes and physiologic variables. Conclusion. This gene polymorphism PPARGC1A Gly482Ser may be a potential marker for increased risk of CAD in diabetic patients in clinical treatment and diagnosis in clinical treatment and diagnosis in the Iranian population.

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.

The beta 3 agonists have antiobesity, thermogenetic and lipolytic properties. Starting from BRL35135 structure, a well-known beta 3 agonist, 3 new phenylethylamine derivates (A, B, C) and 2 new pyrazol derivates (D, E) were synthesized.\r\nPurpose. The aim of this study was to evaluate the effect of five new compounds derived from of BRL35135 on glycemia in normal and diabetic rats.\r\nMethods. For each experiment, test and control groups of 6, 8 or 10 male Wistar rats were used. For inducing experimental diabetes mellitus, alloxan (100 mg/kg body weight) was intravenously injected. Tested substances were intraperitoneally injected (1 or 100 mg/kg body weight) and glycemia values were measured before and at 3 hours after their administration. Control groups received propyleneglycol, the solvent of the new compounds. Glycemia values were measured with a calibrated glucometer.\r\nResults. In normal rats one of the phenylethylamine compounds (substance C) (100 mg/kg body weight) had a hypoglycemic effect comparative to control (p=0.03). In glucose tolerance test, substance E (100 mg/kg body weight) stopped the increase of glycemic values determined by glucose oral administration in the first 60 minutes comparative to control (p=0.03). In the alloxanic diabetes model, before insulin administration the substances hypoglycemic effect could not be measured with the glucometer because of very high values of glycemia. After insulin administration no significant differences between the treated and the control groups were registered. Further studies on the hypoglycemic effect of substances C and E are needed in order to establish their possible antidiabetic effect.\r\nConclusion. A phenylethylamine derivate and a pyrazol derivate of BRL35135 had a hypoglycemic effect in normal rats, but this effect could not be confirmed in rats with alloxanic diabetes.

Leptin is much more than a simple sensor of body fat levels. Its biological activities, include angiogenesis, osteogenesis and modulation of the immune and reproductive systems. There are no reports on fluctuations of the level in normal human functional glandular epithelium during the menstrual cycle. Objective. We aimed to determine the expression level of the leptin receptor by immunohistochemistry and to correlate this with estrogen and progesterone receptor levels in normal endometrial tissue throughout the menstrual cycle. Study design. Thirty-seven paraffin wax blocks of biopsy specimens of histologically normal endometrium were evaluated and classified according to the stage of the menstrual cycle during the 2004–2006 period. Results. The OB-R level underwent fluctuations during the menstrual cycle in the different tissue compartments; these were most marked in the functional glandular epithelium and during the proliferative stage. OB-R levels were correlated positively with the expression levels of estrogen and negatively with those for progesterone receptors, suggesting that these steroids modulate the expression of OB-R in vivo. Conclusion. This finding underscores the importance of considering the menstrual cycle stage for studies seeking possible impacts of the OB-R on reproductive pathology, because its expression level varies with the hormonal environment.

Primary Hyperaldosteronism is one of the causes of secondary hypertension. Primary Hyperaldosteronism is characterised by an increase in the production of aldosterone and the inhibition of the secretion of renin. We described here a case with rhabdomyolysis and severe hypokalemia as a cause of primary hyperaldosteronism. The creatine kinase, aldosterone were very high. Cortisol values and midnight salivary cortisol values were within normal range. The patient had been under treatment for high blood pressure for more than six years, with ARBs and calcium channel blockers. During this time the potassium values measured frequently every year were below normal range, but primary hyperaldosteronism was not suspected.

Background. Coronary artery disease (CAD), often asymptomatic, is the most common cause of morbidity, mortality and costs in diabetes. Early detection of CAD in patients with diabetes may be of paramount importance and substantially improve the outcome in diabetic patients. Objective. The aims of the current study were to determine if there are significant differences concerning the prevalence of occult CAD in asymptomatic type 2 diabetic patients compared to asymptomatic nondiabetic patients. Design, subjects and methods. The authors retrospectively reviewed a group of 120 non-diabetic (77 men, 43 women, mean age 61±10.2 years) and 120 diabetic (81 men, 39 women, mean age 58±11.4 years) asymptomatic patients that underwent coronary computed tomography angiography (CCTA) for various reasons between January 2013 and January 2014. Results. Coronary plaques were identified in 105 diabetic patients (87.5%) and in 75 non-diabetic patients (62.5%) the prevalence being significantly different (p=0.023). Regarding plaque composition and degree of stenosis, we found a higher prevalence of calcified (p=0.016) and significantly stenotic (≥50% luminal narrowing) plaques (p=0.008) in the diabetic group. Agatston calcium score, relevant for atherosclerotic plaque load, was higher (p=0.005) in type 2 diabetic patients (350.3) compared to non-diabetic patients (158.7). Conclusion. CCTA could represent a screening method able to detect silent atherosclerotic plaques thus contributing to the prevention of acute coronary syndrome (ACS) by an early and adequate treatment of CAD. Obstructive atherosclerotic plaques can be accurately identified using CCTA, limiting the use of invasive imaging methods and selecting patients that could benefit of coronary revascularization.

Introduction. Clinical or subclinical hypothyroidism dictates the severity of depressive episodes and more frequently overlaps psychotic phenomenology. There are also major depressive episodes resistant to treatment in patients with euthyroidism, in which supplementation of antidepressant medication with thyroid hormones is beneficial. Material. Systematization of meta-analyses from perspectives: hypothyroidism and depression, autoimmune and depression pathology, gestational and puerperal pathology in association with hormonal and dispositional changes, presentation of therapeutic schemes. Results. Hypothyroidism is more commonly comorbid with major depression in women. It associates the need for hospitalizations, psychotic phenomenology, resistance to treatment, somatic comorbidities. Autoimmune pathology is associated with depression and requires thorough investigation. A possible genetic candidate for thyroid dysfunction is the DIO1 gene. FT4 may be a predictor, but the combination of FT4 + TBG measured during the prenatal period has a higher prognostic power for a future depressive episode. Conclusion. The article presents psychiatric medication schemes that combine antidepressants and antipsychotics of various classes with other enhancers, an important role going back to step three, which includes thyroid hormones, mainly T3. The doses used are smaller than the amount of endogenous production of T3 daily, with a small risk of inducing clinical hyperthyroidism.

Background. Warthin-like papillary thyroid carcinoma (WLPTC) is an uncommon variant of thyroid papillary carcinoma. To date, only 104 cases have been reported in the English literature. Case report. We present a case of WLPTC in a 72-year-old female and we review of the literature on the topic. Clinical evaluation revealed nontoxic multinodular goiter. A total thyroidectomy was performed and pathology examination showed WLPTC, a relatively rare variant of PTC occurring predominantly in older women. It is important to differentiate it from other variants of PTC, particularly from Hürthle cell carcinoma and tall cell carcinoma because the latter two carry a worse prognosis. Conclusion. Treatment, clinical course and prognosis of WLPTC is similar to that of classical PTC.

Objective. To find out the relationship of thyroid hormone profile of females with outcomes after intra cytoplasmic sperm injection (ICSI). Method. It was a cross sectional study conducted in Islamabad Clinic Serving Infertile Couple from June 2013 till August 2015. T3 (triiodo thyronine), T4 (thyroxine) and TSH (thyroid stimulating hormone) of 168 consented females was estimated after they underwent the first step of treatment protocol (ovarian down regulation) for ICSI. Pregnant group had ß hCG result more than 25 IU/mL while the rest were included in the non-pregnant group. Both groups were compared by using independent sample t-test. Pearson correlation coefficient was used to associate T3 and T4 with other pregnancy variables with their significance. Results. Non pregnant women had significantly higher mean values for T3 and T4 as compared to pregnant women (p <0.05, p<0.01). Difference in mean TSH value between non-pregnant and pregnant women was not significant p=0.08. It was found that T4 gave significant negative association with grading of embryo-I, blastocysts formed, thickness of endometrium and number of gestational sacs. Conclusion. Disturbance in thyroid profile with raised T4 levels leads to alteration in endometrial thickness and quality of embryos required for implantation and hence conception.

Background. The cytotoxic T lymphocyteassociated molecules-4 (CTLA-4) is related to the relapse of Graves’ disease (GD) after anti-thyroid drugs (ATDs) withdrawal. We performed a meta-analysis to generate large-scale evidence on whether the CTLA-4 exon 1+49A/G polymorphism can predict the relapse of GD after ATDs withdrawal. Methods and Results. The PubMed, EMBASE,the Cochrane Library and reference lists of relevant studies were searched to identify eligible studies from inception to Jan, 2021. Ten eligible studies consisting of 1450 GD patients with a total of 848 relapsed patients were included in the meta-analysis. In Caucasians patients, the CTLA-4 exon 1+49A/G polymorphism significantly elevated the relapse risk of GD in additive (OR = 2.07, 95% CI: 1.18-3.62, P=0.011), dominant (OR = 2.52, 95% CI: 1.17-5.41, P=0.02), homozygote model(OR = 3.264, 95% CI: 1.25-8.52, P=0.016), except recessive (OR = 2.18, 95% CI = 0.98-4.86, P = 0.062) and heterozygote model (OR = 2.141, 95% CI = 0.958-4.786, P = 0.064). In Asian subgroup, none of these genotypes show any associations with the relapse of GD after ATDs withdrawal. Conclusion. This meta-analysis suggests that the CTLA-4 exon1 +49A/G polymorphism is associated with the relapse risk of GD after ATDs withdrawal in Caucasians, not Asians. Compared with the AA genotype, Caucasian patients with GG genotype have 3.264 times risk of relapse. A more aggressive treatment such as radioactive iodine or thyroidectomy, or longer periods treatment of ATDs should be recommended in Caucasian patients with the GG genotype.