ACTA ENDOCRINOLOGICA (BUC)

In some humans, the big and big-big prolactin variants represent the majority of circulating prolactin, considered to be without biological activity. Aims: to establish the clinical expression of macroprolactinemia and the interference with immunodiagnostic tests\r\nin a randomized group of 84 consecutive patients with hyperprolactinemia. IRMA and electrochemiluminescence (Elecsys) were used for PRL assay; gel filtration chromatography (GFC) and protein A precipitation test were used to reveal macroprolactinemia. Results: Macroprolactinemia was found in 16 out of 84 patients (group A), 62 patients had hyperprolactinemia of other causes (group B) and 6 had normal PRL levels and normal GFC (group C). Of 16 patients with macroprolactinemia, 6 showed normal PRL with IRMA and hyperprolactinemia with Elecsys. The difference between the two methods used (&#8710; = PRL determined by Elecsys, -PRL determined by IRMA) correlated with big big PRL level determined by GFC with Elecsys in all patients. The strongest correlation was found in patients with macroprolactinemia (group A, r=0.82, p<0.01) as compared with group B, without macroprolactinemia (r=0.39, p<0.01). Menstrual disorders were expressed, but less frequent in group A versus B (3/15 vs. 28/56, p=0.04), and the appearance of galactorrhea and infertility were not statistically different. Conclusions: In these patients, macroprolactinemia had clinical expression, but weaker than in true hyperprolactinemic patients. It determines high apparent variability of serum PRL level in current commercial assays.

Introduction. Vitamin D deficiency has been proven to have a deleterious effect on bone remodeling and bone mineral density, by inducing secondary hyperparathyroidism. The lack of a present consensus on optimal serum 25(OH)D levels required for the preservation of physiologic bone metabolism renders its follow-up difficult.\r\nMaterials and Methods. The cross-sectional study was performed on a sample of 69 healthy men aged 50-70. Serum 25(OH)D, total testosterone, sex hormone binding globulin, s-CTX (Crosslaps), and osteocalcin were assessed. BMD was measured by DXA at lumbar spine and hip levels. Statistical relationships between these parameters were calculated.\r\nResults. We found a significantly negative correlation between 25(OH)D and s-CTX (r = -0.30. p<0.05), but not between 25(OH)D and osteocalcin, although s-CTX correlated positively with osteocalcin (r = 0.49, p<0.001). Serum CTX was negatively correlated with lumbar BMD (r = -0.35, p<0.001), while osteocalcin was negatively correlated with total hip BMD (r = -0.26, p<0.01). Comparing mean s-CTX levels in insufficient and sufficient subjects at different cut-off points for 25(OH)D, significant differences appeared the strongest at 60 ng/ml. The percentage of 25(OH)D deficient or insufficient subjects was 50.7% at a 30 ng/ml cut-off point.\r\nConclusions. The results of the present study confirm the benefit in maintaining a normal bone turnover offered by serum 25(OH)D in the upper normal range. The large percentage of patients with vitamin D insufficiency reinforce the necessity of a specific follow-up and of epidemiologic studies dedicated to our geographic area.

Context. Persistent inflammation and impaired neovascularization are important contributors to the development of diabetic retinopathy (DR). Gene polymorphisms of adiponectin (APN) were demonstrated to have an important role on the plasma level and activity of adiponectin. APN has anti-inflammatory, anti-diabetic and anti-atherogenic properties. Toll-Like Receptor 4 (TLR4) is a critical mediator of innate immunity. Polymorphisms in TLR-4 gene were shown to be associated with impaired inflammatory response in diabetes. Objective. The aim of the study was to analyze the association of +276G>T variant of APN gene and Asp299Gly and Thr399Ile of TLR-4 gene variants in relationship with T2DM and DR in an Eastern European population group. Design. The distribution of the mutant alleles in 198 T2DM patients with DR and 200 non-T2DM controls was examined. Genomic DNA from T2DM patients and healthy controls genotyped through the use of PCR-RFPL assay. Results. Genotype and allele frequencies of the Asp299Gly and Thr399Ile polymorphisms differed between T2DM patients and non diabetic subjects (P<0.001). Moreover, the presence of the minor alleles of these polymorphisms were significantly identified as protective factors against T2DM, under a dominant model of Fisher’s exact test (χ2=4.988, phi=0.745, OR=0.767, 95% CI=0.602-0.867, P<0.001; respectively χ2=5.254, phi=0.820, OR=0.487, 95% CI=0.211- 0.648, P<0.001). Genotype analysis for the adiponectin 276G>T gene polymorphism yielded no significant association with T2DM, but revealed a borderline significance for the association with DR (χ2=5.632, phi=0.423, OR =1.101, 95% CI=0.887-1.203, P=0.009). Conclusions. We found an association between the TLR4 Asp299Gly and Thr399Ile polymorphisms and protection for DR. The APN genetic polymorphism is not associated with T2DM.

Objective. This study aims to determine the frequency and prognostic significance of lactic acidosis in children with diabetic ketoacidosis (DKA) admitted to the pediatric intensive care unit. Methods. The study was carried out retrospectively by examining the patients admitted to the pediatric intensive care unit for the treatment of DKA. The ages of the patients ranged from 2 to 18 years. The patients with the following parameters were enrolled in the study: serum blood glucose>200 mg/dL, ketonuria presence, venous blood gas pH ≤7.1, bicarbonate <15. Results. A total of 56 patients were included in the study with a mean age of 111.07 ± 51.13 months. The recovery time from DKA was 16.05 ± 6.25 h in the group with low lactate level and it was 13.57 ± 8.34 h in the group with high lactate level with no statistically significant difference. There was a negative correlation between lactate levels and the recovery time from DKA. Conclusion. Lactic acidosis is common in DKA, and unlike other conditions, such as sepsis, it is not always a finding of poor prognosis that predicts the severity of the disease or mortality. We think that high lactate may even protect against possible brain edema-cerebral damage in DKA.

Aims. Resistin has been reported to impair the pancreatic beta cells and associated with insulin resistance. MicroRNAs (miRNAs) are short, endogenously produced non-coding ribonucleotides that bind mRNAs and function mainly as negative regulators in mammals. MiRNAs have been implicated in many diseases, including insulin resistance and diabetes. A considerable body of evidence has indicated an important function for miRNAs in insulin secretion. The current study was designed to investigate the effects of miR-494 in the reductions in insulin secretion attributable to resistin. Methods. Insulin secretion was determined by ELISA, and expressions of genes were identified using quantitative RT-PCR (qRT-PCR) or Western blot analysis. Results. Insulin secretion was significantly reduced by resistin. Overexpression of miR-494 inhibited insulin secretion both in diet culture and high glucose medium in MIN6 cell lines. MiR-494 down-regulated the protein level of STXBP5 by pairing with sites in the 3′UTR. Conclusion. miR-494 is involved in the insulin secretion regulated by resistin via its effects on STXBP5 in MIN6 cells.

Objective. To characterize serum chemerin levels in obese patients with gestational diabetes mellitus (GDM). Design. Case–control study. Subjects and Methods. Forty seven obese women with newly diagnosed GDM at 24-28 weeks of pregnancy and 32 age, body mass index- and gestational age-matched, normal pregnant women were included. Metabolic patterns and serum chemerin concentrations were measured. Results. Serum chemerin levels were significantly higher in subjects with GDM as compared to healthy pregnant controls (p < 0.05). Fasting insulin was similar between the two groups. HOMA-IR tended to be higher in GDM group but did not reach statistical significance. Women with GDM had significantly higher triglyceride (p < 0.01) and lower highdensity lipoprotein cholesterol (p < 0.001) than controls. In multiple linear regression analyses, chemerin was significantly associated with BMI (beta-coefficient = 0.274, p = 0.01), HbA1c (beta-coefficient = 0.327, p < 0.01), HDL-cholesterol (beta-coefficient = -0.307, p < 0.01), triglyceride (betacoefficient = 0.236, p < 0.05), insulin levels (beta-coefficient = 0.236, p < 0.05) and HOMA index (beta-coefficient = 0.283, p = 0.01). Conclusions. Maternal chemerin levels were significantly increased in GDM at 24-28 weeks of pregnancy. The physiological significance of elevated serum chemerin in GDM remains unclear.

Objectives. The exact pathogenesis of the endometriosis is not apparent. MicroRNAs (miRNAs/miRs) are non-coding RNAs that regulate gene expression at the posttranscriptional level. MicroRNAs can be used a diagnostic and therapeutic tools in different disorders such as endometriosis. MiR-181 has a function in embryo implantation. The main aim of this study is to evaluate the expression of miR-181 and its relationship with HOXA11 gene expression in ectopic and eutopic endometrium tissues in women with endometriosis. Study design. Thirty-four women participated in this study. Ectopic tissue samples (N=17) were collected via laparoscopic surgery, and eutopic tissue samples (N=17) were obtained from an endometrial biopsy. Endometrial tissue samples without endometriosis were considered the control group. Tissue samples were placed in RNase-free microtube with RNAlater™ Stabilization Solution (Thermo Fisher Scientific) and were kept at -80 ¯C. Quantitative real time-PCR for MiR-181 and HOXA11 genes were performed. Results. MiR-181 expression level increased in eutopic tissue samples compared to the control group. This expression showed a significantly decrease in an ectopic group compared to the eutopic group. It was observed that HOXA11expression decreased remarkably in eutopic group compared to the control group and increased in ectopic group compared to the eutopic group. Conclusion. MiR-181 and HOXA11 are promising strategies in endometriosis disease. Understanding this relation and regulation roles contribute to realizing the etiology of endometriosis.

Background. The pro-thrombotic potential of the anabolic androgenic steroids (AAS), worldwide misused substances, has increasingly become a subject of current interest. Conversely, taurine, a sulfur-amino acid ubiquitous in human body, in addition to other beneficial effects, is thought to have an inhibitory effect on platelet aggregation. Purpose. To assess platelet aggregation both taurine and high doses of AAS were simultaneously chronically administered in rats. Methods. The experiment was conducted on 40 male Wistar rats, divided into 4 equal groups: control (C) – no treatment; AAS (A) – treated with 10 mg/kg/week of nandrolone decanoate (DECA); taurine (T) – daily treated with oral supplementation of 2% taurine in drinking water; androgen and taurine group (AT) – concomitant administration of DECA and taurine. After 12 weeks of treatment, blood samples were collected and platelet aggregation induced by ADP was performed using the turbidimetric method. Results. The platelet aggregation magnitude was significantly higher (p<0.001) in group A (62.1±6.10%) than in group C (47.8±5.39%), while in group T (40.3±6.49%) it was significantly lower (p=0.04). Moreover, the platelet aggregation response was significantly lower in group AT (54.5±6.38%) than in group A (p=0.04), without a significant difference between group AT and group C (p=0.08). Conclusion. Our findings provide additional evidence regarding harmful potential of high doses of DECA, chronically administered. The increased platelet aggregation induced by AAS may be decreased by diet supplementation with taurine.

Vitamin D deficiency and insufficiency are common medical problems worldwide as they\r\nare quite prevalent in both healthy adults and individuals with osteoporosis, hospitalized patients\r\nand free-living and institutionalized elderly. The lack of serum 25-hydroxy-vitamin D (25OHD)\r\nassays standardization, variability of reference population, and the use of different cut-off points\r\nhave produced quite different prevalence reports from epidemiological studies.\r\nWe investigated the vitamin D status (deficiency, insufficiency, sufficiency) in 1048\r\nRomanian postmenopausal women with osteoporosis referred to our clinic for diagnosis and\r\ntreatment in the last three years. Most patients were untreated with osteoporosis drugs and nonsupplemented\r\nwith vitamin D. In our country dietary sources of vitamin D are scarce and there\r\nis no fortification of food with vitamin D. We found a high prevalence of both vitamin D\r\ndeficiency (25OHD < 10 ng/mL) - 22.23% and insufficiency (25OHD=10-30 ng/mL) - 61.26%.\r\nOur study also revealed a high prevalence of low vitamin D when using other cut-offs as reported\r\nin the literature. 83.49% had values lower than 30 ng/mL and 60.97% lower than 20 ng/mL. In\r\nthis study we identified a serum 25OHD concentration of 35 ng/mL above which serum\r\nparathyroid hormone (PTH) concentration attains a plateau at about 35 pg/mL. The relation\r\nbetween serum PTH and 25OHD concentration was non-linear and a log-log diagram showed a\r\nvery weak correlation. The prevalence of secondary hyperparathyroidism was 32.25% in the\r\nwhole population studied. It ranged from 40% in the subgroup of serum 25OHD less than 10\r\nng/mL to less than 15% in patients with 25OHD higher than 30 ng/mL.\r\nIn conclusion, in a representative osteoporosis population from Romania we found a very\r\nhigh prevalence of vitamin D deficiency and insufficiency whatever the cut-off used for\r\ndefinition.

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.