ACTA ENDOCRINOLOGICA (BUC)

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.

In this study we aimed to evaluate and quantify optic nerve damage caused by long standing compressive pituitary macroadenomas with conventional (ophthalmoscopy) and modern techniques such as fundus camera, confocal scanning laser tomography for quantitative measurements of the thickness of retinal layers as well as visual evoked potentials (VEP) for electrophysiological quantification. Seven patients with large, long standing pituitary macroadenomas were submitted to ophthalmologic evaluation, including a visual field (VF), visual acuity (VA) and eye fundus (F). Heidelberg retinal tomography (HRT) was used for retinal thickness and evaluation of nerve fibers loss, and VEP were measured by pattern reversal and flash stimulus. In addition, all patients underwent tumor imaging (MRI/CT) and specific endocrine evaluation. All cases presented with macroadenomas with suprasellar extension and residual or progressive optic chiasma syndrome; all but one (prolactinoma) were nonfunctioning adenomas, after radical treatment (surgery ? radiotherapy). Adrenal and thyroid substitutive treatment was instituted in all cases due to associated pituitary failure. Evaluation of VF showed 9 eyes with temporal hemianopia, 2 with nasal islands of vision and 1 with nasal hemianopia in a homonymous hemianopia case; another case presented for left 3rd nerve palsy due to a cavernous sinus syndrome, therefore the visual field was not measurable in 2 eyes. Visual acuity was very low (counting fingers) in 4 eyes, while in the rest the VA was between 0.5-0.9. The fundus revealed total atrophy in 2 eyes, band atrophy in 4, temporal pallor in 5 and global pallor in 1. Cup/disk ratio in the case with 3rd nerve palsy was 0.5 (RE) and 0.3 (LE). HRT II stereometric analysis of the optic nerve head showed abnormal values, documenting retinal nerve fiber layer (RNFL) loss that correlated with fundus appearance and visual field defects. Mean RNFL thickness had abnormal values in 8 eyes (from 0.074 to 0.173 μm), correlated with RNFL cross sectional area in 7 eyes (from 0.362 to 0.846 μm2) and 1 eye with low limit values (1000 μm2). In agreement with these data, VEP–P100 presented increased latency over 120 ms in 8 eyes, borderline (100-120 ms) in 5 and 97.5 ms in only 1 eye. In conclusion, HRT can document the papilla and nerve fiber layer more objective, permitting quantification of the disc’s alterations due to compressive pituitary macroadenomas. HRT is useful in quantifying RNFL loss in other conditions than glaucoma, when other optic disc imaging tools are not available.

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.

Purpose. The aim of the study was to investigate whether the circulating miR-132, miR-146a, miR-222, and miR-320 levels are used in the differential diagnosis of women with polycystic ovary syndrome (PCOS) and healthy women. Methods. This prospective case-control study included 50 women with PCOS and age- and body mass index- matched 50 healthy controls. The hormone and lipid profiles, levels of microRNAs (miRNAs), and parameters of carbohydrate metabolism were measured. Results. Expression levels of miRNAs were assessed using the two-step quantitative real-time polymerase chain reaction. Circulating miR-132, miR-146a and miR- 222 levels were significantly downregulated in the PCOS group compared with the control group. The miR-320 levels did not differ between the two groups. Free testosterone was negatively correlated with miR-132, miR-146a and miR-222. Insulin was negatively correlated with miR-132 and miR-146a. Conclusions. The results of the study revealed that miRNA expression, may suggest a possible distinction between healthy women and PCOS patients. miR-132, miR-146a, and miR-222 may have key functions in the pathogenesis of PCOS.

Context. Hypoxic exposure has been associated with a metabolic perturbation that might affect basal energy expenditure (BEE). Objective. The aim was to examine the metabolic response during hypoxic exposure of men and women adults. Design. Crossover design with two experimental trials: normoxic and hypoxic exposure. Subjects and Methods. Twenty-nine healthy subjects (14 women) participated in (1) control study (NOR), subjected first to normoxic exposure (FiO2 = 20.9%) and (2) after that, to passive normobaric hypoxic exposure study (HYP) (FiO2 = 15%). Respiratory gases and blood glucose samples were recorded every hour in hypoxia chamber (8 points in total), and blood lactate samples were collected at baseline, at 4 and 7 h to exposure. Results. In females, basal energy expenditure was significantly higher at 2h, 4h, 6h and 7h compared with NOR group. Also, BEE was lower in females compared with men from 2h of hypoxia exposure. In the HYP group the blood lactate concentration increased significantly at 4h and 7 h relative to NOR group (P < 0.05) in males. Conclusion. An exposure to moderate normobaric hypoxia did not alter metabolic response, but induced a different response on substrate oxidation in adults men and women.

Objective. Data about iodine status in pregnant women in Turkey is not sufficient. We aimed to determine the iodine status, goiter prevalence, iodized salt consumption among first trimester pregnant women living in Edirne. Design and Setting. Cross-sectional study was performed on pregnant women living in Edirne. Subjects and Methods. A total of 275 pregnant women in their first trimester were examined regarding iodized salt use, median urinary iodine concentration (UIC), presence or absence of goitre and thyroid function. Goitre status was determined by palpation. Participants filled out a questionnaire, which included questions regarding sociodemographic features, iodized salt consumption, knowledge, and behavior regarding iodine deficiency. UIC was measured using colorimetric method based on Sandell–Kolthoff reaction. Thyroid hormones and TSH were measured by chemiluminescence immunoassays. Results. While the proportion of iodized salt use was 96.6%, UIC was below 150 μg/L in 88.4 % of the women. The median UIC was 77 μg/L, indicating insufficient iodine intake. Total goitre rate was 19.3%. Conclusions. Our study shows that iodine deficiency is a serious problem among pregnant women in Edirne. We suggest that pregnant women living in Edirne should be supplemented by iodine-containing preparations in addition to iodized salt.

Aim. The aim of this study is to present the personal experience of the authors regarding the use of positron emission tomography-computer tomography fusion image (PET/CT), with 18Ffluoro-2-deoxy-D-glucose (FDG), in the follow-up of differentiated thyroid carcinoma (DTC).\r\nPatients and Methods. Twenty seven cases of DTC admitted and treated in the &#8220;Prof. Ion Chiricu??&#8221; Institute of Oncology Cluj-Napoca (IOCN), performed PET/CT investigation\r\nbetween 2007 and 2009, in DOTE Centre Debrecen (Hungary) and Pozitron Center Oradea (Romania). The patients underwent the surgical intervention and had histology of differentiated carcinoma; they received radioiodine therapy with I-131, had suppression therapy with thyroid hormones and had in the follow-up whole body scans (WBS) with I-131, neck ultrasound and serological determination of thyroglobulin (Tg) and anti-thyroglobulin antibodies (anti-Tg). All patients were referred to PET/CT after radical treatment, after a negative WBS I-131 and a dynamic increase of the serological level of Tg or anti-Tg, without any clinical signs of\r\nrecurrence and no neck ultrasound pathological findings.\r\nResults. All patients included in this study presented abnormal levels of Tg: between 2.76 ng/ml and 4173 ng/ml, with a median value of 43.15 ng/ml. In 23 cases (85.1%) the PET/CT results revealed the neoplasm recurrence, in 3 cases we obtained true negative results and in 1 case a false negative image; in 2 cases (7.4%) we found a second malignancy. All patients needed to change the treatment strategies.\r\nConclusion. The significant increase of the number of DTC and the more aggressive behaviour of the disease in some situations, determines the existence of a clear strategy of\r\ntreatment and monitoring, where the role of PET/CT is well defined.

Context. Thyroid disorders are common in diabetics and related to severe diabetic complications. TRPV2 ion channels have crucial functions in insulin secretion and glucose metabolism which have an important role in the pathophysiology of diabetes. Also, they have a significant effect on various immunological events that are involved in the HT pathophysiology. Objective. This study aimed to investigate rs14039 and rs4792742 polymorphisms of the TRPV2 ion channels in type 2 diabetes mellitus (T2DM, n=100) Hashimoto thyroiditis (HT, n=70) and comorbid T2DM and HT (T2DM+HT, n=100) patients and control (n=100). Design. Case-control study Subject and Methods. RT-PCR genotyping was used to determine rs14039 and rs4792742 polymorphisms with DNA samples of subjects and appropriate primer and probes. Besides, required biochemical analyses were performed. Results. It was determined that the frequencies of the rs14039 GG homozygote polymorphic genotype and the G allele were significantly higher in T2DM+HT patients compared to the control (p=0.03 and p=0.01, respectively) and that especially the GG genotype increases the risk of T2DM+HT 3.046-fold (p=0.01, OR=3.046). It was detected that the GG genotype increased the risk of HT 2.54-fold (p=0.05, OR=2.541). TRPV2 rs4792742 polymorphisms reduce the risk of HT and T2DM+HT comorbidity almost by half and have a protective effect against HT and T2DM+HT. Conclusion. The rs14039 GG genotype of the TRPV2 gene significantly increases the risks of development of T2DM+HT and HT disorders, may have a significant role in the pathophysiology of these diseases, also leading to predisposition for their development. Conversely, rs4792742 polymorphic genotypes have a strong protective effect against the HT and T2DM+HT comorbidity.

Context. Chronic stress is characterized by increased release of catecholamines, glucocorticoids and other neurohumoral factors, predisposing individuals to obesity, insulin resistance and vascular disease, pathologies considered priority health problems. Study of alterations induced by stress on metabolism in association with food intake modulatory hormones (insulin, leptin and ghrelin) is mandatory. Objective. This research studied temporal course during 60 days of chronic unpredictable mild stress (CUMS) on glucose and lipids metabolism, and on the neuroendocrine system that regulates appetite-satiety balance. Materials and Methods. Wistar rats were exposed to CUMS for 20, 40 and 60 days. Corticosterone stayed high during 60 days of CUMS; after 40 days, body weight, cholesterol and triglycerides decreased and glucose intolerance was evident at day 60; insulin and ghrelin increased at 20 and 40 days, respectively; leptin decreased after day 20. Data suggest that 60 days of CUMS progressively disturb metabolism of carbohydrates and lipids as well as food intake regulatory hormones, affecting the metabolism, and can lead to the development of chronic degenerative diseases, such as cardiovascular disease, metabolic syndrome and type 2 diabetes.

Context. Oxytocin has been investigated as a potential medication for psychiatric disorders. Objective and design. This study prospectively investigates correlations between oxytocin and other neuropeptides plasma levels in patients with autism spectrum disorders (ASD) according to severity and treatment, as compared to controls. Subjects and methods. Thirty-one children (6 neurotypical as control) participated in this study. The patients were classified into mildly and severely-affected, according to Autism Diagnostic Observation Schedule (ADOS) scores. Oxytocin, orexin A and B, α-MSH, β-endorphins, neurotensin and substance P were investigated using a quantitative multiplex assay or a competitive-ELISA method. Results. Plasma oxytocin levels differed between the groups (F (2, 24) =6.48, p=0.006, η2=0.35, observed power=86%): patients with the mild ASD had higher values of plasma oxytocin than those with the severe form (average difference=74.56±20.74pg/mL, p=0.004). Conclusions. These results show a negative correlation between plasma levels of oxytocin and the severity of ASD and support the involvement of oxytocinergic mechanisms in ASD.