ACTA ENDOCRINOLOGICA (BUC)

Smith-Lemli-Opitz syndrome is an autosomal recessive disorder caused by mutations of 3-hydroxysterol –7reductase gene (DHCR7) which maps to 11q12-13 and was the first discovered defect in cholesterol biosynthesis resulting in a congenital dysmorphology syndrome. We present the case of a 46,XY newborn with ambiguous genitalia and multiple congenital anomalies (atrial septal defect, ventricular septal defect, syndactyly of the second and third toe, cleft palate, webbed neck, small fontanels, mesomelia, simian palmar crease, micrognathia, wide nasal bridge with anteverted nostrils, low set ears). Hormonal assessment performed at twelve days revealed a decreased testosterone level (0.03 ng/mL), a high estradiol level (448.8 pg/mL), normal LH (2.8UI/mL), DHEAS (86.61?g/dL), progesterone (1.34ng/mL) and 17 hydroxyprogesterone (1.08ng/mL) levels. Cholesterol was low (44mg/dL) confirming the diagnostic of Smith-Lemli-Opitz syndrome.

Recent studies indicate a relatively high prevalence of hypogonadism with low gonadotropin levels, in adult male patients with type 2 diabetes (T2DM).\r\nObjective.In this study we investigate the possibility of a predisposition to hypogonadism and its relationship with\r\ninsulin resistance and leptin levels in adolescent and young males with one or both diabetic parents.\r\nDesign. It was a cross-sectional study conducted on male subjects between 15-25 y of age.\r\nSubjects & Methods. Groups of subjects with one diabetic parent (n=30) and with both diabetic parents (n=30) were\r\ncompared with an equal number of age matched offspring of healthy non diabetic parents (n=30). Fasting blood glucose,\r\nserum insulin, leptin, FSH, LH and testosterone were measured.\r\nResults. Mean fasting insulin, and insulin resistance as assessed by HOMA-IR, were significantly higher (p<0.05) in offspring of both diabetic parents and mean serum leptin\r\nlevels were significantly higher (p<0.001) in both groups of offspring of diabetic parents compared to that of the control group. Whereas serum testosterone concentrations\r\n(p<0.05) were lower in both groups of offspring with diabetic parents, serum LH was higher (p<0.05) in offspring of both diabetic parents, as compared to control group. Also, serum testosterone levels were shown to be inversely related to serum leptin in subjects with both diabetic parents.\r\nConclusion.The present study suggests evidence of hypoandrogenesis in subjects with a family history of T2DM and the possibility of a direct effect of factors such as\r\nhyperleptinemia and hyperinsulinemia on androgenesis at an early age, independent of changes in pituitary function.

Context. Gender identity, psychosexual function, psychiatric adjustment and quality of life have been investigated in congenital adrenal hyperplasia(CAH) patients. Objective. We aimed to investigate gender identity problems and the psychiatric disorders and associated factors in children and adolescents with CAH patients. Subjects and methods. Forty-five children and adolescents with CAH were included in the study. Psychiatric comorbidity was assessed using the Schedule for Affective Disorders and Schizophrenia for School Age Children – Present and Lifetime Version. Gender identity problems were investigated using the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition criteria. Results. The mean age of the sample was 11.02 years (SD: 3.25, range: 6–18). 51.1% of the patients had at least one lifetime comorbid psychiatric disorder. The most common diagnoses were anxiety disorders, attention deficit hyperactivity disorder(ADHD), tic disorders and enuresis nocturna. Tic disorders and ADHD were higher in males but they were not statistically significant. Two female patients were diagnosed with gender dysphoria and 18.5% of females showed variably masculinized behaviors. The girls with gender identity problems expressed lower satisfaction with their sex than other girls and boys. Conclusions. Children and adolescents with CAH had many psychiatric disorders, especially neurodevelopmental disorders. ADHD and tic disorders should be kept in mind during assessment especially in male patients. Gender dysphoria and masculine behaviors seem to be common in female patients with CAH so they should be carefully investigated.

Background. Thyroid nodules are common; however, the association of two or more different tumors in the thyroid gland is unusual. We present a first case with the association of three histological types of thryroid tumors. To the best of our knowledge, this association has not been reported in the literature before. We aim here to highlight the possible coexistence of many lesions in the thyroid gland and to discuss treatment options. Case presentation. We report the case of a female patient who presented with a multinodular goiter. The final pathology after total thyroidectomy found the association of a multifocal papillary thyroid microcarcinoma arising within a Hurthle cells adenoma in a lobe and a noninvasive follicular thyroid neoplasm with papillary nuclear features in the other lobe. Due to the very low risk of recurrence, the patient was not treated with radioactive iodine. Conclusions. Many controversies remain about the management of Hurthle cells tumors and many variants of papillary thyroid carcinoma. Although the management of our case did not change, more studies are necessary to analyze the evolution of patients with multiple thyroid neoplasms. When discussing therapeutic options, the advantages and disadvantages should be considered case by case based on disease staging.

The prerequisite for developing methods for type 1 diabetes mellitus prevention is to know its pathogenic mechanisms. The aim of this work was to characterize a group of children with type 1 diabetes mellitus regarding pancreatic antibody positivity and fasting C peptide concentrations. The study group enrolled 117 children, 61 boys (52.1%), mean age 12.7?3.1 years. Islet cell antibodies, glutamic acid decarboxylase antibodies (GADA), IA-2 antibodies (IA-2A) and fasting C peptide were measured. Sensitivity for GADA and IA-2A tests was 85% and 75%, respectively. Specificity for the tests was 87.1% and 98%, respectively. The threshold for pancreatic antibody positivity was considered the 97.5th percentile, and normal values for fasting C peptide were between the 5th and 95th percentiles from a control group (n=73), matched for age and gender. Thirty-nine patients (33.3%) were positive for 1 antibody, 10 (8.6%) were positive for 2 and 2 (1.7%) were positive for all 3 antibodies. The positivity for pancreatic antibodies and for islet cell antibodies was significantly lower in patients with diabetes duration>2 years, compared with the rest: 32% vs. 52.2% (p=0.03) and 6% vs. 20.9% (p=0.03), respectively. Mean fasting C peptide and the percentage of patients with normal C peptide decreased significantly one year after the diagnosis of diabetes: 0.20?0.40 ng/ml vs. 0.44?0.57 ng/ml (p=0.03) and 9.5% vs. 27.3% (p=0.02), respectively. In conclusion, in children with type 1 diabetes mellitus, pancreatic autoimmunity is more intense in the first two years of the disease and insulin secretion decreases one year after the diagnosis.

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Introduction. Graves’ disease (GD) and concomitant thyroid nodules can be found in up to 44% of all cases, of which up to 17% are determined as malignant tumors. Medullary thyroid carcinoma (MTC) seems to be found extremely rarely, which causes belated diagnosis. Case presentation. A 50-year-old man was diagnosed with GD. Neck ultrasound revealed suspicious thyroid nodule, a fine needle aspiration biopsy was performed, and it revealed microfollicular hyperplasia, Bethesda IV. The patient was operated on and the histological examination confirmed MTC. Genetic testing revealed the sporadic form of MTC. Six weeks after the initial surgery, elevated tumor markers confirmed the persistence of the disease. The patient underwent a pyramidal lobe removal with a unilateral central compartment lymph node dissection. Histological analysis confirmed typical changes of MTC and a spread of the disease. 2 months after the lymphadenectomy, tumor markers and imaging examination revealed suspicious lymph nodes; this discovery was followed by a bilateral lymph nodes dissection and persistence of MTC confirmation. Conclusion. An early detection of sporadic MTC with concomitant GD is challenging. We want to emphasize the benefits of calcitonin (Ctn) measurement in the blood sample and a Ctn immunocytochemistry detection in the case of an autoimmune thyroid disease and suspicious thyroid nodule before the radical treatment, despite the lack of universal recommendations for routine Ctn measurement, in order to reach an earlier diagnosis of the cancer, and to perform a more radical surgical treatment.

Context. Diabetes is one of the causes of cardiovascular damage because it increases production of free radicals. Antioxidants, such as vitamin E (vit E), have been tested for efficacy in defending against free radical mediated tissue injuries. Objective. We aimed to investigate the effect of vit E on oxidative stress status and homocysteine (Hcy) in cardiac tissue of diabetic rats. Subjects and Methods. Sixteen Wistar male rats were treated with streptozotocin (STZ) (60 mg/kg) to induce diabetes. Diabetic rats were divided into two groups: non-treated diabetic (NTD) and vit E-treated diabetic (VETD) rats. The VETD group received 300 mg/kg vit E with daily feeding. Eight normal rats of the same age were used as the control group. After 6 weeks, the rats were anesthetized, their cardiac tissue was removed, and homogenated supernatant was separated. Samples were assayed for total antioxidant capacity (TAC), lipid peroxidation (LPO), nitrite (NO2-), nitrate (NO3-) and homocysteine (Hcy). Results. The contents of LPO, NO3- and Hcy in NTD compared to control group indicate a significant increase, but the levels of these parameters decreased in VETD (P<0.05). There was a significant decrease in the amount of TAC in the NTD group but in VETD group, that significantly increased (P<0.05). The amount of NO2- in NTD and VETD groups, compared to the control group, did not show any significant changes (P>0.05). Conclusions. Significant decrease in the cardiac tissue oxidative stress and Hcy resulted from vit E supplementation strongly indicated that this radical scavenger may promote a protective effect on diabetic cardiomyopathy through the attenuation of oxidative stress and increase antioxidant defense mechanism.

Background. Exposure to methotrexate (MTX) causes infertility in young women treated for non-neoplastic\r\ndiseases. Leucovorin an antidote to MTX is used to prevent its side effects. Reproductive tract cells are fast proliferating like cancer cells. Hence, MTX may cause deleterious effect on these cells.\r\nAim. Explore MTX effect on biochemical markers and the protective role of leucovorin in the accessory reproductive\r\norgans viz; oviduct, uterus, cervix and vagina.\r\nAnimals and Methods. Rats with regular oestrous cycle were randomly divided into five groups (n=6) as follows:\r\nControl, MTX LD (low dose), MTX HD (high dose), MTXHD+LCN (leucovorin, LCN), and MTXHD+WD (withdrawal): 20 days withdrawal. Animals were treated once per day intramuscularly (im) for 20 days. Rats were sacrificed on day 21. MTXHD treatment was withdrawn for additional 20\r\ndays and animals sacrificed on day 41. Oviducts, uterus, cervix and vagina were used for biochemical markers analysis.\r\nResults. MTX treatment decreased RNA, DNA and protein concentrations. Such similar effects were also observed in\r\nG6PD, LDH and ALP activities. Leucovorin and withdrawal of treatment partially recovered MTX effects. Uniquely, this study signifies MTX action on nucleic acids and protein levels and also G6PD, LDH and ALP activities in oviducts, uterus, cervix and vagina.