ACTA ENDOCRINOLOGICA (BUC)

Central precocius puberty (CPP) is characterized by abnormalities in the setting up of the gonadotropin ?pubertal? release, which occurs earlier. The gonadotropin releasing hormone (GnRH) was used initially to test the pituitary regarding FSH and LH release in both precocious and delayed puberty. Various GnRH superagonists were used for the same purpose, including triptorelin. A triptorelin test was applied to 14 girls with premature thelarche by using the subcutaneous administration of 0.1 mg/sqm and blood sampling at 2, 3 and 4 hours for serum LH and FSH and at 24 hours for serum estradiol. Serum mean levels of LH were >7.8 mIU/ml at all intervals, suggesting a ?pubertal? type of LH release. As concerns the individual levels of LH, only 5 out of 14 girls showed a value greater than 8 mIU/ml, which is the cutoff limit for the diagnosis of precocious puberty. These girls also met the other clinical and radiological criteria necessary for the diagnosis of precocious puberty. It was concluded that soluble triptorelin may be useful in detecting ?pubertal? type of LH release in girls exhibiting premature thelarche. Regarding the FSH and estradiol levels, they were considered irrelevant for the diagnosis.

Background. Chronic kidney disease (CKD) and type 2 diabetes mellitus (T2DM) are associated with disturbed mineral homeostasis and serum bone biomarkers. The interplay between T2DM and CKD on serum bone turnover markers (BTM) is unclear. Our aim was to describe the BTM in patients with T2DM, CKD or both. Methods. In this observational, single-centre, prospective study, we included 320 patients over 40 years, divided into four groups: T2DM and normal kidney function (n=142), T2DM and CKD (n=36), CKD and normal glucose metabolism (n=29) and healthy controls (n=113). We excluded patients treated for osteoporosis and with secondary osteoporosis. Patients were compared by age, levels of glycated hemoglobin, PTH, alkaline phosphatase, osteocalcin (OC), CTx and 25 OH vitamin D. Results. Univariate analysis showed that GFR correlated significantly with PTH (r=0.37), OC (r=0.43) and CTX (r=0.45) in the diabetes group but only with PTH (r=0.34) in the non-T2DM group. Multivariate analysis showed that GFR remained significantly correlated with the same bone markers even after adjustment for age, sex or 25(OH)D levels. Diabetics seem to have lower levels of alkaline phosphatase (68±22.1 U/L) and CTX (0.37±0.24 ng/mL) than those without diabetes (76.7±29.6. U/L and 0.5±0.19 ng/mL, respectively). There was no correlation between BTM and glycated hemoglobin. Conclusions. Bone turnover markers correlate with GFR, particularly in patients with T2DM. However, alkaline phosphatase is lower in T2DM than in non-T2DM.

Aims. This study investigated the relationship between proteinuria levels, clinicopathological features, and renal prognoses in Chinese patients with type 2 diabetes mellitus (T2DM) and diabetic nephropathy (DN). Methods. Three hundred patients with T2DM and biopsy-proven DN were enrolled. Patients were stratified by 24-h proteinuria levels: Group 1:≤1g/24h); Group 2:1-3g/24h; and Group 3:≥3g/24h. Renal outcomes were defined as having reached end-stage renal disease (ESRD). The proteinuria level’s influence on the renal outcomes was evaluated using Cox regression analysis. Results. Among subgroups stratified by proteinuria levels, systolic blood pressure, serum creatinine, BUN, cholesterol, DR and hypertension incidence, the incidences of patients who progressed to ESRD were the lowest in group 1 (P<0.05). However, eGFR, serum albumin and hemoglobin were highest in group 1. Patients with higher proteinuria levels had much lower five-year renal survival rates. Univariate analyses revealed that higher proteinuria levels were significant clinical predictors of renal prognosis (P<0.05), although they were not independent risk factors for progression to ESRD in the multivariate Cox proportional hazard analysis (P>0.05). Conclusions. The higher the level of proteinuria, the lower the 5-year renal survival rate of DN patients, but there was no significant correlation between proteinuria level and 5-year renal survival rate. Other factors in the proteinuria group may have more significant effects on the 5-year renal survival rate, such as lower baseline eGFR, serum albumin, hemoglobin and higher cholesterol, higher incidences of DR and more severe lesions.

Background and aims. Severe Ovarian Hyperstimulation Syndrome (OHSS) forms with very aggressive clinical evolution are still common, despite prophylactic measures. Besides the Vascular Endothelial Growth Factor (VEGF), there are other angiogenic factors, like Renin-Angiotensin-Aldosterone System (RAS), that might be associated with this disorder. Our study aims to evaluate the role of VEGF and Angiotensin II (ANG II) in the development of early severe OHSS, in high risk patients under prophylactic Cabergoline therapy. Material and Methods. We recruited 192 patients undergoing in vitro fertilization (IVF) procedures with high risk for OHSS development. Out of these, 106 patients with OHSS were enrolled in the study, of which 28 subjects had a severe form of disease (group I), and 78 patients had a mild/ moderate form (group II). We collected blood and follicular fluid from our study participants and determined serum and follicular VEGF and ANG II levels using Enzyme-Linked Immunosorbent Assay (ELISA) technique. Results. Follicular VEGF, ANG II, and serum VEGF levels were significantly higher in group I versus group II. Serum VEGF titers were 645.97 versus 548.62 (p = 0.0008), follicular VEGF titers were 2919.52 versus 1093.68 (p < 0.0001), and follicular ANG II levels were 281.64 versus 65.76 (p < 0.0001). No significant differences have been shown between the two groups for serum ANG II levels. Conclusion. Our study results provide evidence of a OHSS phenotype that is more prone to undergo severe clinical forms of disease, despite treatments with VEGF receptor blockers, and show that ANG II appears to play a major role alongside VEGF, in the development of these severe forms of disease.

Background and Aim. Ischemia-reperfusion (I/R) injury frequently occurs in different situations. Female sex hormones have a protective function. The purpose of this study was to determine the function of female sexual hormones on the gastric damage induced by I/R in male rats. Methods. Forty (40) Wistar rats were randomized into five groups: intact, ischemia- reperfusion (IR), IR + estradiol (1mg/kg), IR + progesterone (16 mg / kg) and IR + combination of estradiol (1mg / kg) and progesterone (16 mg/ kg). Before the onset of ischemia and before reperfusion all treatments were done by intraperitoneal (IP) injection. After animal anesthesia and laparotomy, celiac artery was occluded for 30 minutes and then circulation was established for 24 hours. Results expressed as mean ± SEM and P <0.05 were considered statistically significant. Results. The Glutathione (GSH) concentration significantly decreased after induction of gastric IR (P<0.001). Estradiol (P<0.001) and combined estradiol and progesterone (P<0.001) significantly increased GSH levels. The myeloperoxidase (MPO) concentration significantly increased after induction of gastric IR (P<0.001). Different treatments significantly reduced MPO levels (P<0.001). The gastric acid concentration significantly increased after induction of gastric IR (P<0.001). Treatment with estradiol, progesterone (P<0.05) and combined estradiol and progesterone (P<0.01) significantly reduced gastric acid levels. Superoxide dismutase (SOD) concentration decreased after induction of gastric IR. The SOD levels were not significant. Conclusion. These data suggested that female sexual steroids have a therapeutic effect on gastrointestinal ischemic disorders by reduction of MPO and gastric acid, and increasing gastric GSH & SOD levels following gastric IR.

Context. Patients with radically treated differentiated thyroid carcinoma (DTC) undergo multiple episodes of iatrogenously-acquired hypothyroidism for the oncological follow-up. In some patients, this elevates high-sensitive C-reactive protein (hsCRP), a cardiovascular risk biomarker. Objective. We wanted to determine if there is any correlation between repeated hypothyroidism episodes, elevated hsCRP and an increased cardiovascular risk as stated through myocardial perfusion. Design. Between July 2014-January 2015, we analyzed serological levels of hsCRP for identifying our patients’ cardiovascular risk; we performed a myocardial perfusion scintigraphy to observe the alterations. Subjects and Methods. We included 27 patients (n=27), mean age of 52±10: CI (95%),14 female, all diseasefree after thyroidectomy, radioiodine ablation and chronic thyroid hormone treatment. We assigned the cardiovascular risk category for each patient according to hsCRP levels; all patients underwent a myocardial perfusion scintigraphy in order to determine the cardiac perfusion index (CPI). Results. hsCRP has been higher in > 65 years old male patients with more than 5 thyroid hormone withholdings. hsCRP is significantly associated with CPI (p=0.001). Spearman’s rank correlation indicates a strongly positive linear correlation between these two parameters (r=0.745). Conclusions. Repeated thyroid hormonal withdrawals in patients with DTC during the long-term follow-up elevated hsCRP at cardiovascular risk levels, having an impact on myocardial perfusion.

Introduction. There is increasing evidence that 5’ adenosine monophosphateactivated protein kinase (AMPK) signaling pathway plays a role in bone physiology. The aim of the present study was to investigate the effect of a drug activating AMPK, namely metformin, on ovariectomy-induced osteoporosis in the rat. Methods. The present study was conducted on 40 female Wistar albino rats that were divided into 4 groups of 10 rats each, Group I: sham operated, Group II: non-treated ovarictomized (OVX) rats, while groups III and IV were OVX rats treated with metformin and metformin plus a substance that inhibits AMPK, namely compound C, respectively. At the end of the experimental period, urine and blood samples were collected and used for determination of urinary deoxypyridinoline (DPD) serum: osteocalcin, calcium and phosphorus concentrations and serum alkaline phosphatase activity. Biochemical assessment of AMPK activity in isolated fourth lumbar vertebrae (LV4) was carried out. The tibia, left femur and third lumbar vertebrae (LV3) were weighed and biomechanical study on LV3 was carried out. Immune histochemical studies of right femur and the forth-lumbar vertebrae (LV4) were carried out using anti-Fas antibodies to detect apoptotic osteoclastic and osteoblastic cells. Evaluation of cortical bone morphometric indices was done by CT-Scanning technique. Results. The results of the present study demonstrated that metfromin protected against biochemical, histological, biomechanical and histomorphometric osteoporotic changes. Compound C, an inhibitor of AMPK, blocked metformininduced changes in assessed parameters suggesting that the effect of metformin was mediated mainly through activation of AMPK. Conclusions. Drugs modulating AMPK could be effective in ameliorating OVX-induced osteoporotic changes.

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.

Background. Insulin resistance (IR) is a component of type 2 diabetes and metabolic syndrome and it increases in the presence of chronic inflammation. Lately, “neutrophilto- lymphocyte ratio” (NLR) has been used as an indicator of inflammation. This study evaluates the association between IR and NLR in obese women. Material and methods. Obese female patients who were followed up in a university hospital for the last two years were included in the study. Homeostasis model assessment of IR (HOMA-IR), C-peptide, NLR, bioelectrical impedance measurements of 83 patients were analyzed. Results. The C-peptide levels of our patients showed a highly significant correlation with HOMA-IR (p<0.001). A significant positive correlation was found between fasting plasma C-peptide levels and NLR (r=0.36 and p<0.003) in obese women. The increase in C-peptide levels had a significant effect on the increase in NLR (r2=0.31, p=0.002), however insulin had no similar effect on NLR (r2=0.01, p=0.544). Conclusion. Plasma C-peptide levels are better correlated with NLR compared to other parameters of IR. C-peptide may be used as an efficient laboratory marker with high relevance in IR and chronic inflammatory conditions in obese women.