ACTA ENDOCRINOLOGICA (BUC)

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.

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.

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.

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.

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.

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Context. Increased arterial stiffness is an independent risk factor of cardiovascular events in patients with diabetes mellitus (DM). Objective. We aimed to evaluate elastic properties of common carotid arteries (CCA) in patients with DM type 1 (T1DM) by means of ultrasonographically based technique – two-dimensional speckle tracking. Design. Case-control observational study. Subjects and Methods. Examination of both CCA was performed in 50 patients with T1DM. The mean age of patients was 36.1 (±11.9) years and duration of diabetes was 8.9 (±11.9) years. 28 controls (mean age 38.6 ± 10.8) were examined according to the same protocol. Strain and strain rate reflected arterial wall stiffness and intimamedia complex thickness (IMCT) indicate presence of morphological changes. Parameters were compared between groups and regression analysis was performed to predict determinants of evaluated parameters. Results. Patients with T1DM had significantly more elastic CCA arteries than the healthy control (mean strain [%]: 6.05 ± 2.55 vs. 5.19 ± 1.79, p=0.0295; mean strain rate [1/s]: 0.91 ± 0.33 vs. 0.78 ± 0.25, p= 0.0142; respectively), but no significant differences in IMCT were revealed (0.49mm ± 0.12mm vs. 0.49mm ± 0.10mm, p=0.9893; respectively). Women had significantly decreased strain parameters in comparison with men, although the difference in IMCT was not significant. Conclusions. Two-dimensional speckle tracing revealed increased elasticity of CCA in patients with T1DM with no deterioration of arterial wall.

Introduction. The published data showed the importance of metabolic control in preventing complications in metabolic syndrome (MS) and the role of nutritional medical therapy in glycemic control and in the control of dyslipidemia, hypertension, weight loss/normalization (in overweight or malnourished subjects). Objectives. This study follows the evolution of sarcopenic index (SI) and other clinical parameters (body mass index (BMI), homeostasis evaluation index (HOMA index)) correlated with MS after diet therapy or diet therapy combined with sports, in patients with MS. Patients and methods. Our research was conducted during 12 months, on 110 patients >18 years of age, with HOMA index>2, divided into three groups: control group (CG, N=20), diet therapy group (DTG, N=58), diet therapy and sports group (DTSG, N=32). HOMA index for insulin resistance was calculated as the product of resting plasma insulin (in microunits/milliliter) and plasma glucose (in millimoles/liter), divided by 22.5. SI was determined using BIA, as being the ratio between muscle mass and fat mass, measured in cm2 /m2 . Results. A significant decrease of BMI (p<0.05) in DTG (from 31.63 to 24.50) and DTSG (from 30.18 to 24.17) vs. CG was observed (Pearson coefficient r=0.281, p<0.001). Weight status changed significantly (p<0.05) in the high-risk patients. There was a significant decrease of HOMA index (p<0.05) in DTG (from 5.93 to 2.57), DTSG (from 3.93 to 2.23), and in CG an increase was observed (from 3.15 to 3.37). Conclusion. The best results in the prevention/ treatment of sarcopenia in MS patients were obtained for DTSG, which benefited from both the positive effect of diet and physical activity.

About 15-20% of adults with Down?s syndrome have autoimmune hypothyroidism. Among patients with Down?s syndrome, prevalence of Graves disease (1-2%) may not be increased compared with the general population. About 15% of the patients with Turner?s syndrome have autoimmune hypothyroidism. Until 2006, only 15 cases of Graves disease have been reported among patients with Turner?s syndrome. We present two adult patients with chromosomial disorders (Down?s syndrome, Turner?s syndrome) with Graves? disease without clinical Graves ophthalmopathy. Clinical picture of thyrotoxicosis was oligosymptomatic in the patient with Down?s syndrome, probably because Down?s syndrome represents a syndrome of accelerated ageing. Both were pretreated with antithyroid drugs before radioiodine therapy. Both patients developed postradioiodine hypothyroidism: after 8 months in the case with Turner?s syndrome and after 11 years in the patient with Down?s syndrome. Adults with these two chromosomial disorders should be screened annually for autoimmune thyroid dysfunction.