ACTA ENDOCRINOLOGICA (BUC)

Context. There are evidences that excessive production of reactive oxygen species is one of important abnormalities that contribute to development of chronic diabetic complications. Objective. To test the effect of intensive insulin therapy with analogues through the examining the level of oxidative stress parameters. Subjects and Methods. Comparison of data obtained by prospective analysis in 49 patients with T1DM was used, before and after six months of intensive insulin analog therapy. Results. The values of all three investigated parameters of oxidative stress malondialdehyde (MDA); xanthine oxidase (XO) and nitrates and nitrites (NOx) in our population with T1DM compared to the control (group of 42 voluntary blood donors) are statistically higher. The levels of antioxidant protection parameters compared to the control group also differ; the activities of catalase and glutathione peroxidase (GPx) are statistically higher in our population of T1DM patients compared to the control and superoxide dismutase (SOD) activities are statistically lower. The values of all three examined parameters of oxidative stress decrease after six months of intensive insulin analog therapy and were statistically lower after the therapy: for MDA p<0.001, for XO p<0.01 and for NOx p<0.05. The activities of catalase (p<0.001) and GPx (p<0.01) both decrease with therapy, while the activity of SOD is highest after the sixth month of therapy (p<0.001). Conclusion. In our patients with T1DM compared to the control the level of oxidative stress is significantly higher. Intensive insulin analog therapy with aspart and glargine promotes predominantly the improvement of oxidative stress, and in a less degree antioxidant protection.

Our study aimed to evaluate clinical, endocrine and genetic aspects in three patients with Noonan syndrome and to establish genotype – phenotype correlations. Noonan syndrome is a frequent autosomal dominant disorder, characterized by distinctive facial features, short stature, congenital heart defects, unusual chest shape, broad/ webbed neck, cryptorchidism and developmental delay. GH therapy initiated early adds 1 SD to final adult height. We have identified common features that are very suggestive for the diagnosis, as well as the changing of facial aspect in time. In case 2 we recorded a milder phenotype than expected for KRAS mutations. In case 3 we identified new features (severe scoliosis and ventricular septal defect) as well as more severe clinical features than expected for SOS 1 mutations. We have detected particular patterns of growth in our patients before and after GH therapy. Unlike literature data, our PTPN11 mutation positive child reacted very well to GH, whereas our KRAS mutation positive case started to gain Ht only after 3 years of GH therapy. We have recorded hypertrophic scars either as a new feature of NS, or as a possible adverse event of GH therapy. GH therapy was successful in our patients, without classical adverse events recorded. Somatotropic axis dysfunction is discussed.

Context. Genetic factors are responsible for up to 80% of height variation in humans. SHOX gene mutation could be an important etiologic factor in short stature, being observed in up to 15% of patients. Aim. Our aim was to evaluate the genetic causes of short stature, using classical and molecular cytogenetic techniques by analyzing a group of Romanian patients diagnosed with short stature. Material and methods. Seventy nine patients were analyzed and the main criteria for inclusion in the study was the presence of a height below -2DS. For each of these patients a karyotype was performed. In those with normal karyotype it was indicated FISH technique using probes for SHOX and centromeric regions. Results and discussion. The karyotype revealed the presence of abnormalities in 13 patients (16%), 62% (8 patients) of these being represented by heterosomal abnormalities. SHOX deletion was seen in one patient (2.3%) with short stature and normal karyotype. The initial analysis of the cases with short stature directly by FISH technique can be proposed, using probes for X chromosome centromere and SHOX gene, because it allows, approximately at the same costs with the karyotype, but faster and at a higher rate of mosaicism detection, the explanation of short stature by sex chromosomes abnormalities.

Background. The loss of reproductive function is one of the mostimportant adverse effects of chemotherapy. Folic acid deficiency may be harmful in pregnancy. Hence, it is imperative to investigate if leucovorin (LCN), a folinic\r\nacid supplementation and withdrawal of MTX treatment facilitate maintenance of pregnancy in albino rats.\r\nAim. The aim of this study was to examine the role of leucovorin (LCN) and withdrawal of MTX treatment in the\r\nprotection of pregnancy at very early stage of pregnancy in MTX treated rats.\r\nAnimals and Methods. Rats with regular oestrous cycle were randomly divided into five groups (n=6) as follows: Control,\r\nMTXLD (low dose), MTXHD (high dose), MTXHD + LCN (leucovorin), and MTXHD + WD (withdrawal). Animals were treated intramuscularly (im) on days 1-5 of pregnancy. MTXHD treatment was withdrawn and female rats showing regular cycle were caged with male rats. Laparotomy was performed on day 8 of pregnancy to note the number of implantation sites. Rats were sacrificed on day 20.\r\nResults. MTX significantly reduced maternal weights, number of corpora lutea, and implantation sites. 100% foetal\r\nresorption was prevalent in MTX treated groups. LCN supplementation did not help maintain pregnancy. While approximately 45% foetal resorption was observed in\r\nwithdrawal group.

A 20-year-old woman was studied because of lack of spontaneous pubertal development and primary amenorrhea. At the moment of examination in the Medical Genetics Department she had normal height, sparse axillary and pubic hair, but breasts were well developed (she already had some estrogen therapy). She had normal but infantile external genitalia, normal vagina and small uterus. Laparoscopic investigation suggested the presence of gonadoblastoma in the dysgenetic gonads and histopathologic examination confirmed the diagnosis. The karyotype revealed a 46, XY chromosome constitution in lymphocytes, without structural defects of X or Y chromosomes. Because of the risk of malignancy, gonadectomy was performed.

It is known that antithyroid drugs have been associated with development of agranulocytosis or secondary autoimmune neutropenia. Aplastic anemia is an unusual but severe form of haematological complication after antithyroid drugs. We are presenting a case of a 34-year old woman diagnosed with Graves&#8217; disease, based on ophthalmopathy, symptoms and signs of hyperthyroidism, a diffuse enlargement of the thyroid gland; TSH level= 0.17 mU/L, fT4= 28 pmol/L, T3= 4.92 nmol/L, thyroglobulin antibodies= 117 IU/mL. The patient developed, after six weeks of treatment with Carbimazole 60 mg daily, a moderate aplastic anemia (pancytopenia: haemoglobin level= 8.2 g/dL, granulocytes= 800/mmc, platelets= 40,000/mmc; hypocellular bone marrow with increased fat cells and lymphocytosis, plasmocytosis and mastocytosis, in the absence of neoplastic or infectious infiltrations, possibly with immune aetiology suggested by disturbance of CD4/CD8 and favourable response after immunosuppressive therapy). Therapy was represented by: stopping the administration of carbimazole, broad spectrum antibiotics, antiviral and antifungal prophylaxis,general and dental hygiene, high doses of methylprednisolone followed by Cyclosporin A 12 mg/kg/day, with favourable evolution. The serum T3 and T3/T4 ratio increased after the antithyroid drug regimen was stopped . After 3 months of therapy, the patient was in complete haematological response with haemoglobin value= 11.8g/dL, granulocytes= 2.200/mmc, platelets = 130,000/mmc and was submitted to subtotal thyroidectomy.

Background and Objectives. Levels of insulin-like growth factor-I are characteristically low in Laron syndrome which is a factor that has important roles on vascular health and development. Congenital insulin-like growth factor-I deficiency was reported to be associated with some vascular disorders. However, vasculitis diseases and Laron Syndrome association has not been reported in English literature up to date. Patient. We report the case of a two and a half years old Turkish girl, who was diagnosed as Laron syndrome when she was 12 months old. She presented with acute vasculitis lesions. Her physical examination and laboratory studies did not reveal a specific infectious agent or also an autoimmune disease was not detected. Her lesions disappeared during hospitalization without a complication. Conclusion. Since insulin-like growth factor-I reduces endothelial cell oxidative stress and maintains the structural integrity of vessels, some common mechanisms might be responsible for the occurrence of vasculitis in this patient with Laron syndome. The role of insulin-like growth factor-I and recombinant human insulin-like growth factor-I treatment choice in vasculitis diseases is a matter of investigation.

Objective. To study papillary thyroid microcarcinomas (PTMCs) detected incidentally/non-incidentally, especially those with suggestive signs for progression into clinically overt forms.\r\nMaterial and methods. In the first part of study 102 microcarcinomas diagnosed between 1988-2008 were investigated. In the second part we included all the 311 patients thyroidectomized for different thyroid diseases in surgical clinics from T?rgu Mures in 2007.\r\nResults. During 1988-2008 the frequency of PTMCs increased progressively, achieving a peak in 2007 (46.5% of 58 PTCs). In 2007 from the 311 thyroidectomies 27 microcarcinomas were diagnosed, the majority (70.3%) being incidentalomas. In incidental and non-incidental PTMC groups the rate of microcarcinomas with potential progression into overt carcinomas was 21% and 50%, respectively. Only non-incidental forms with signs of progression were treated by total thyroidectomy in every case, while microincidentalomas\r\njust in about half of cases, although all must be treated the same way.\r\nConclusions. After the Chernobyl nuclear accident and use of modern diagnostic methods (ultrasound and FNA) the frequency of PTCs has increased progressively and\r\nsignificantly, including that of microcarcinomas diagnosed mostly incidentally. We must pay attention for PTMCs, because in our casuistry 29.6% harbored suggestive signs\r\n(multifocality, extrathyroidal extension, regional lymph node metastases) for progression.

Objective. Opium is a narcotic drug that is commonly abused. The prescription of pharmaceutical derivatives of opium is limited due to their possible harmful effects on the body’s metabolism and tolerability by patients. The aim of the present study was to evaluate the effects of chronic opium consumption on some sexual and thyroid hormones in diabetic and non-diabetic male and female rats. Material and Methods. This experimental study was conducted on 56 Wistar rats. The animals were divided into diabetic addicted (DA), diabetic non-addicted (DNA), non-diabetic addicted (NDA) and non-diabetic non-addicted (NDNA) groups of male and female rats. Peripheral blood samples were collected to measure the thyroid and sex hormone levels. Student’s t-test was used to compare the mean values of the hormones between two groups. Results. T3 serum level in male addicted groups significantly increased in comparison with non-addicted ones in both diabetic and non-diabetic groups. The testosterone level of male rats decreased due to the consumption of opium while it was significantly increased in diabetic and NDNA female rats in comparison with non-addicts. In DNA female animals, the mean level of 17-hydroxyprogesterone increased significantly compared with non-diabetic groups, however, it decreased in addicted females (diabetic and non-diabetic) in comparison with non-addicts. The level of DHEA-S increased significantly in diabetic and NDA male rats as compared with the non-addicted group. Conclusion. Opium affects the endocrine system in a sex-dependent manner, and opium could have different effects in diabetic and non-diabetic conditions.