ACTA ENDOCRINOLOGICA (BUC)

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Objectives. The purpose of this study was to evaluate the association between the follicle-stimulating hormone (FSH) receptor (c.-29G>A) and FSH beta chain (c.- 280G>T) polymorphisms and endometriosis in Romanian women. Material and methods. We performed the polymorphic analysis of the FSH receptor gene and FSH beta chain in 44 patients with endometriosis and 34 controls. Genomic DNA was obtained from peripheral blood and polymorphisms were investigated using restriction fragment length polymorphism analysis (RFLP). Results. There were no significant differences in genotype frequencies of FSH receptor gene between endometriosis patients and controls. For the heterozygous type of the FSH receptor polymorphism (c.-29G>A) we did not find a significant difference in its frequency between patients with minimal/mild and moderate/severe endometriosis (p = 0.136). Also, the FSH beta chain (c.- 280G> T) polymorphism frequency was not significantly associated with the severity of endometriosis (p = 0.966). Conclusions. FSH receptor and FSH beta chain polymorphisms do not seem to influence the severity of endometriosis, but they could be correlated with female infertility (primary or secondary), therefore further studies are required to debate this topic.

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Leptin seems to play a significant role in the regulation of pituitary GH secretion. In GH deficient children serum leptin level is higher than in GH sufficient ones. Administration of rhGH resulted in a significant decrease in serum leptin in GH deficient but also in children displaying idiopathic growth delay, small for gestational age at birth, Prader-Willi syndrome and other obese. LBA is in fact the soluble form of leptin receptor. It was previously shown that GH deficient children are mostly hyperleptinemic and that GH induces a reduction in leptin level within 3 weeks of therapy. Such a reduction could serve as a valuable marker of the long term growth response. Twenty short children whose GH status was previously assessed through GH provocative tests and auxological evaluation were explored as concerns IGF I, leptin and LBA. According to these criteria they were classified as GH-deficient and GH-sufficient. Blood samples for the assay of serum leptin and LBA and IGF I were drawn at 8 a.m. A daily dose of 0.35 mg of rhGH was given subcutaneously at 8 pm in 12 of them and the same sampling was done 12 hours after the last injection. A therapy with GH with the same preparation and in comparable weekly dosage was started in all children and the height gain was evaluated after six months. Total serum leptin was assayed by a commercially available sandwich ELISA kit. LBA was assayed by a sandwich ELISA kit using a human IgG-Fc fragment of leptin receptor. IGF I determination was performed by the OCTEIA kit in a two-site immunoenzymometric assay (IEMA). The means and SEM before and after 10 days of GH administration in the whole group were of 3.4 ? 0.71 ng/ml and 1.7 ? 0.16 (p< 0.02) for leptin 0.27.1 ? 0.92 U/ml and 23.6 ?1.66 (ns) for LBA, 48.9 ? 10.65 ng/ml and 84.3 ? 17.61 for IGF I (p> 0.05, ns). Comparison between GH deficient (def) and GH sufficient (suf) subgroups resulted in significant differences as regards initial values for IGF I (20.2 ? 4.21 in def vs 77.6 ? 16.7 in suf, p< 0.02) but not in leptin, LBA, height and weight z scores. After ten days of therapy no significant differences were noted in subgroups for leptin, LBA and IGF I (absolute values), but a striking difference was noted in percentual rise of IGF I in def children. There was a significant positive correlation between leptin basal level and the growth rate in the subsequent 6 months of GH therapy. No similar correlation was noted for IGF I and LBA. It was concluded that hyperleptinemic GH deficient children seem to be particularly sensitive to the growth promoting effect of rhGH at least in the first six months of therapy.

Introduction: Obesity, a disease whose morphological background has as main problem the “dysfunctional” adipocyte, continues to raise scientific interest for the completion of the existing data and the verification of the hypothetic ones. Material and method: We determined insulinemia and glycemia within the oral glucose tolerance test (OGTT), and we analyzed the relation between the fat mass and cortisolemia in a group of 50 obese patients aged between 4 months –18 years. In 19 obese patients, between 5 ½ -17 ½ years old, we determined the basal leptin and resistin serum levels, comparatively to a control group of 19 normal weight children. In 14 obese and 10 normal weight controls, we determined the number of androgenic and estrogenic adipocyte receptors, which we correlated with the degree of obesity, the Tanner stage and respectively the testosterone, progesterone and estradiol serum levels. We studied the cellularity, morphohistochemical and ultrastructural features of the adipose tissue in 42 obese and 20 normal weight controls. Leptin and resistin were determined by ELISA. The measurement of the fat mass was done by bioelectric impedance. For the study of the adipose tissue we took 1g of tissue from the retro-trochanterian area. We identified the estrogenic (ER) and androgenic (AR) receptors by LSAB2 technique. We interpreted the data statistically by the linear regression analysis and variance test “t” for two unequal parameters using Microsoft Excel 2002. Results: A positive correlation was demonstrated between glycemias and insulinemias for the entire group (r=0.927, p=0.002), as well as between cortisolemia and fat mass excess (r=0.917; p=0.001). Serum leptin levels were significantly high in the obese (mean values: 81.07 ng/ml) comparatively to normal weight individuals (mean values: 4.17 ng/ml). Resistin serum levels did not show significant differences between the obese and normal weight individuals. We cannot talk about the existence of any correlation between resistin and leptin.

A certain degree of insulin resistance in patients with Gaucher disease type 1 (GD) under enzyme replacement therapy (ERT) was reported. Data on insulin sensitivity in treatment naïve patients are inconsistent. Objective. To analyse prospectively changes in parameters of insulin resistance under ERT and to estimate when they occur. Design. prospective, controlled study; three years follow-up. Patients and methods. 12 treatment naïve patients with GD type 1 (M/W 8/4), 29.5±12.9 years, without overweight, diagnosed enzymatically and by genotyping, without previous diabetes mellitus. Patients were evaluated before and every 6 months up to 3 years under ERT and compared at baseline and after 3 years with matched healthy controls. Fasting-glucose (FG), - insulin (FI), C-peptide, HOMA-IR, IRI, HOMA-B, blood count, hepatic and splenic volume, chitotriosidase, severity score index di Rocco (SSI) were assessed. Results. Baseline glycemic parameters did not differ from controls. FG increased from baseline after two years of ERT (+16.4%,p<0.010), FI (+40.3%,p=0.030), HOMA-IR (+61.2%,p=0.007) and IRI (+9.1%,p=0.010) after 18 months, HOMA-B after 2.5 years (+51%, p=0.015. After 3 years of ERT patients were more insulin resistant compared to controls (p<0.001): FG (96.0±6.2 vs. 73.2±6.4 mg/dL), FI (11.2±2.4 vs. 5.6±1.3 μU/L), HOMA-IR (2.7±0.6 vs. 1.0+0.3), IRI (3.02±0.10 vs. 2.62±0.13). FG, FI, HOMAIR, IRI, HOMA-B correlated with disease severity markers. Conclusions. This is the first controlled study which evaluates prospectively insulin resistance in GD patients, finding significant differences compared to baseline starting with 18 months ERT.

Context. The prevalence of patients with concomitant heart failure (HF) and diabetes mellitus (DM) is high. Objective. To analyze the role of NT-pro-BNP levels in the evaluation of diabetic patients with heart failure. Design. Retrospective comparative cohort study. Subjects and Methods. A total of 174 patients admitted to our Cardiology Department, previously diagnosed with HF, were enrolled. Among these patients, 47.7% had DM. HF was defined according to the 2016 ESC criteria. The NT-pro BNP levels above 126 pg/mL indicate a high probability of heart failure. Results. In diabetic patients there were significant correlations between NT-pro-BNP values and the following parameters: hemoglobin (rho=-0.28, p=0.01), hematocrit (rho= -0.27, p=0.014), total cholesterol (rho= -0.21, p=0.048), triglycerides (rho= -0.283, p=0.01), ejection fraction (rho= -0.465, p<0.0001), end-diastolic volume (rho= 0.253, p= 0.026), end-systolic volume (rho= 0.29 p=0.01). Only the following 3 parameters: ejection fraction (p= 0.0009), hemoglobin (p= 0.0092) and triglycerides (p= 0.0380) were independent predictive factors for elevated NT-pro-BNP values. Conclusion. In diabetic heart failure patients, the value of NT-pro-BNP holds a pivotal role in the evaluation of their overall status, facilitating the establishment of correct management and follow-up.

We present the case of severe hypocalcaemia in a 5 weeks old baby, secondary to pre and postnatal vitamin D deficiency. The symptomatic hypocalcaemia led to several life threatening episodes of seizures. Following initial calcium gluconate infusion, multiple phospho-calcic deposits in the soft tissue and cerebral tissue were observed. A multifactorial etiology of calcinosis cutis was suggested by the association between infusion of high and repeated doses of calcium gluconate in a severely hypocalcaemic baby, with a low 25- hydroxyvitamin D3 level, associated to a renal and bone relative resistance to the high level of PTH. The aim of this report is to raise pediatric health care professionals awareness on the relatively rare entity known as calcinosis cutis.

Context. Patients with diabetes mellitus have high-risk of coronary artery disease that is often silent. NT-proBNP is a\r\nneurohormone that in recent studies proved useful in detecting ischemic heart disease.\r\nThe objective was to evaluate whether NT-proBNP can detect silent myocardial ischemia and can predict cardiovascular outcome and mortality in asymptomatic patients with type 2 diabetes.\r\nMethods. This study was conducted on 250 patients with type 2 diabetes mellitus without known coronary heart disease and heart failure. All patients were evaluated at baseline and were followed-up prospectively for 3 years for major cardiac events. Exercise ECG and Holter ECG were performed for silent ischemia detection. NT-proBNP was determined on a ROCHE cardiac reader.\r\nResults. NT-pro BNP was significantly raised in patients with silent ischemia (p<0.0001) and remained independent and the strongest predictor of silent ischemia in multiple regression analysis (p<0.0001). NTproBNP levels in patients who experienced major cardiac events were significantly higher (p<0.0001). In multiple regression analysis only silent ischemia (p<0.0001, r=0.20) and NT-proBNP (p<0.0001, r=0.67) remained independent predictors for major cardiac events.\r\nConclusions. NT-proBNP can be useful in screening for silent ischemia in asymptomatic type 2 diabetic patients and also is a strong predictor for major cardiac events.

The discovery of the cannabinoid receptors CB1 and CB2 in 1990 and 1993, respectively, as well as of the two main endocannabinoids, anandamide in 1992 and 2-arachidonylglycerol in 1995, was an important step in identifying the strongest homeostatic system in the human body, namely the endocannabinoid system. Ever since, research has highlighted the crucial part played by this system in all the reproduction stages: folliculogenesis, spermatogenesis, oogenesis, fecundation, transport of the egg through the fallopian tubes, blastocyte implantation and pregnancy progression, as well as its implications in the physiopathology of the reproductive system: in endometriosis, ectopic pregnancy, miscarriage, preeclampsia, endometrial cancer, polycystic ovary syndrome, ovarian cancer. A special attention must be paid to the phytocannabinoids, natural components originating especially from the Cannabis plant inflorescences, whose medical effects are wellestablished nowadays with also acting on the receptors of the endocannabinoid system. The most recent research mainly focuses on the reproductive dysfunctions and disorders of the reproductive tissues, respectively, through its action upon the endocannabinoid system. Medical cannabis is nowadays legalized in more and more countries all over the world. At the same time, recreational cannabis remains one of the most consumed drugs (in Romania the most consumed one by young adults). Therefore, it is mandatory for specialists in obstetrics and gynecology, endocrinology, public health, hygiene or for general practitioners, to permanently update their information on this subject.