ACTA ENDOCRINOLOGICA (BUC)

The mechanism underlying anovulation in the polycystic ovary syndrome (PCOS) remains unclear, although an excessive number of small antral follicles at ultrasound scans and discrepancies with selected follicles sustain the hypothesis of altered follicular development. Anti-M?llerian (AMH) hormone is a member of TGF-b super family of growth factors produced by granulosa cells of pre- and small-antral follicle. The 2 to 3 fold increase in the number of growing follicles in the ovary from PCOS women is reflected by an increase in serum concentration of AMH and thus, this hormone may be a good marker of PCOS.\r\nAim. This study was intended to implement ultra-sensitive ELISA measurement of serum AMH from PCOS women and search for a potential correlation with clinical and laboratory parameters.\r\nSubjects and methods. Sera from patients with PCOS (n = 42) and control women (n = 22) were used for ELISA measurement of AMH (AMH-EIA, Beckman Coulter) with sensitivity of 0.7 pmol/L.\r\nResults. We found a serum concentration of AMH almost 3 folds higher in patients with PCOS compared to controls (73.7 ? 7.5 vs. 25.7 ? 3.9 pmol/L, P < 0.0001). Differences were even higher in lean subjects. A positive correlation was found between total testosterone and LH levels, but not with serum FSH or insulin. Moreover, AMH concentration was correlated to more hyperandrogenic PCOS and with amenorrhea, and thus to the severity of the syndrome.\r\nConclusion. Measurement of serum AMH may be used as a valuable marker for PCOS to confirm diagnosis and evaluate the extent of follicular dysfunction in relation with hyperandrogenism and menstrual disturbances.

Vertebrate nonapeptide neurohormones constitute an evolutionarily conserved family, involved in vital functions, such as hydro-osmotic balance regulation, reproduction and social behaviour. Two human members of this family are known, vasopressin (AVP) and oxytocin (OXT), with their highly homologous genes closely located on Chr 20p13. Presence of vasotocin (AVT) in man has been suggested, but remains controversial, and genetic evidence is lacking. AVT activity could be explained by the presence of a third distinct gene for AVT or an RNA-processing mechanism involving products of AVP and/or OXT genes. To test the first hypothesis, we developed bioinformatics and experimental approaches using genomic DNA and fetal tissues mRNAs. Family-specific primers for AVT and neurophysin were designed based on CODEHOP strategy and used in our experiments. Results of bioinformatics and genomic DNA experiments (family-specific and Alu step-out PCR) suggest there is no evidence for an AVT gene in the genome. RNA-based techniques 3?-RACE and Family-Specific Domain Restriction Fragment RTPCR provided evidence for new transcript species that could code for AVT. Further experiments will be needed to characterize them. We discuss potential mechanisms of AVT mRNA generation based on AVP and OXT mRNAs, by alternative splicing, heterologous transsplicing or RNA-editing. While all methods we developed proved feasible, current results suggest there is no AVT gene in the genome, but specific mRNAs could be present in fetal tissues. Their full characterization may potentially allow identification of vasotocin mRNA and shed light on a subject of fundamental scientific interest.

Chronic transfusion regimen and chelating therapy has dramatically improved the life expectancy of thalassemic patients. The aim of this study was to assess the prevalence of endocrine disturbances in patients with beta-thalassemia major. Subjects were 64 patients with a mean age of 19.45 ? 6.82 years found in haematological care at the National Institute of Transfusional Haematology. All the patients were evaluated clinically and biologically. LH, FSH, estradiol, testosterone, TSH, free T4, insulin were measured by chemiluminescence; mean ferritin value was used to assess iron overload. Fifty one patients (79.68%) -27 male and 24 female in our group were at pubertal or adult age. Eleven boys (40.74%) had delayed puberty, 10 (37%) arrested puberty and 4 (14.8%) had reached complete sexual maturation. In the female group, 6 (25%) had delayed puberty, 4 (16.66%) arrested puberty and 14 (58.32%) reached full sexual development. Half of both the male and female patients with complete sexual maturation had hypogonadotropic hypogonadism at the evaluation moment. Moreover, 34 (53.12%) of our patients had pathological short stature, 11 (17.18%) primary hypothyroidism, 5 (7.8%) hypoparathyroidism, 3 (4.68%) diabetes mellitus and 6 (9.37%) insulin resistance. We found a significantly higher mean ferritin value in patients with endocrine disturbances of any type compared to subjects without endocrinopathies. In conclusion, our data showed that hypogonadism and short stature were the most frequently found endocrine disturbances. Early form of hypogonadism had a major clinical impact on sexual development and final height. These results suggest that early endocrine evaluation and treatment are necessary in order to improve the quality of life of these patients.

Vitamin D is essential in efficient absorption of calcium and normal mineralization of bone. Severe vitamin D deficiency produces impairment of bone mineralization and osteomalacia. Less severe vitamin D deficiency, called vitamin D insufficiency or inadequacy, causes secondary hyperparathyroidism, increased bone turnover and bone loss. The aims of our study were: the evaluation of vitamin D status and its seasonal variation in postmenopausal women with osteoporosis, from Romania; we studied also the relationship between vitamin D and parathyroid hormone serum concentrations in order to establish the threshold level of vitamin D which determines secondary hyperparathyroidism. The study was performed on 834 postmenopausal (natural or surgical) women who attended the National Osteoporosis Center and were diagnosed with osteoporosis using dual absorptiometry with X ray (DEXA). None was receiving vitamin D supplementation and they were not taking drugs affecting bone and mineral metabolism and were not suffering from such diseases. Estimation of vitamin D and parathyroid hormone status was made by determining 25-hydroxyvitamin D (25OHD) and PTH-intact (PTH) serum concentrations from a single blood sample using immuno-enzyme methods. The results were compared using Student? t test for unpaired values and linear regression to establish the correlation. All data were expressed as mean value ? standard deviation and a value of p<0.05 was considered as statistically significant. In a previous study we reported for premenopausal normal women the mean value for 25OHD at 26.58?10ng/ml. At the same time, we defined the vitamin D deficiency as the levels below 12 ng/mL, and the insufficiency of vitamin D (vitamin D inadequacy) as the values between 12 and 26.58 ng/mL. The mean serum 25OHD concentration for our study group was 20.04?144.22 mg/mL. We defined arbitrary values (using data from international studies) for 25OHD serum levels to estimate the prevalence of vitamin D deficiency and vitamin D inadequacy in our study group. In 834 postmenopausal women with osteoporosis, living in Romania, without vitamin D supplementation or pharmacological therapy to treat or prevent osteoporosis, the prevalence of vitamin D deficiency was 32.2% and the prevalence of vitamin D inadequacy was 42.3%. Seasonal variation of 25OHD was found statistically significant (p<0.05), with lower values at the end of winter. Statistical tests applied to results have shown a significant negative correlation between PTH and 25OHD serum levels (p<0.001) and established the cut-off concentration for 25OHD which determine secondary hyperparathyroidism at 20 ng/mL. Our data underscore the need for adequate vitamin D supplementation in women with osteoporosis.

Nicolae Paulescu (1869-1930) was born in Bucharest in an aristocratic family. His education from childhood to maturity (Paris University of Medicine) was marked by illustrious professors, even pioneers of their field. After completing his medical and scientific education in Paris under his mentor, Etienne Lancereaux, considered the founder of modern physiology, he returned to Romania where he founded the first Department of Physiology at “Carol Davila” University of Medicine and Pharmacy. His scientific career is marked by the publishing of 88 original research articles in renown international medical journals of the time and two Treatise on Physiology (comprising in total 8 volumes and 5976 pages). His activity as an endocrinologist reaches the peak with the discovery of insulin with the article Recherche sur le rôle du pancréas dans l’assimilation nutritive published in the Archives Internationales de Physiologie (Liege, Belgium) on August 31st, 1921. While he was not internationally or even nationally acclaimed for the discovery of insulin, his contribution to the reformation of the national education and medical system and the recommendation of his students to pioneers of their fields of interest still have reverberations even today.