ACTA ENDOCRINOLOGICA (BUC)

Context. Optical Coherence Tomography (OCT) is a non-invasive diagnostic imaging technique, providing histological-like, high resolution transverse-section images of the eye structures. Objective. To quantify optic nerve’s alterations in optochiasmatic syndrome by OCT and with a classical investigation: visual field. Design. We present a patient with a giant pituitary tumor and chiasmatic compression, first seen in 2013, treated and reassessed in 2014. Subjects and Methods. Patient demanded an ophthalmological exam because of visual disturbances. Ophthalmic exam included: visual field (VF) test (with automated static perimetry – Oculus Centerfield), measurements of the Retinal Nerve Fibre Layer (RNFL) and optic nerve head (ONH) by OCT scans – using a Stratus Zeiss 3000 device. Brain MRI was made and the patient was then assessed by endocrinologist. Results. Patient has bitemporal hemianopia. OCT showed, in both eyes, slight optic disc (ONH) edema and RNFL loss, mainly in the nasal quadrant (optic nerve “band atrophy”), correspondent with visual field temporal defect. Brain MRI and endocrine evaluation revealed a macroprolactinoma, optochiasmatic syndrome, panhypopituitarism and abdominal obesity. Under treatment we noted significant reduction in tumour size, correlated with remission of ONH edema and visual field almost normalized. Reviewed published data about visual field defects and optic nerve OCT measurements, in different types of pituitary tumours, fits well the case presented. Conclusions. OCT is a very useful and accurate objective investigation for diagnosis and follow-up in structural optic nerve changes caused by chiasmatic compression. Measurements are complementary to those provided by perimetry – a subjective, functional investigation, depending on patient skills.

Background. NR5A1 [Steroidogenic factor 1 (SF1)] is a nuclear receptor that is essential for the development of gonads and adrenal glands as well as the establishment of steroidogenesis in these organs. The clinical findings of the mutations of NR5A1 gene in 46, XY individuals are variable. Virilization at puberty can be seen in some of the 46, XY children who have a female phenotype and are raised as female. A girl aged 13 years and 10 months old was brought by the family for deepening of her voice. On physical examination, her breast development was Tanner stage 2, axillary hair (+) and pubic hair was Tanner stage 4. She had labioscrotal fusion and 4.4 cm phallus (External Masculinisation Score was 6). Hypergonadotropic hypogonadism, low AMH and high testosterone levels were detected in laboratory tests. Uterus was not visualized in pelvic ultrasonography. Karyotype analysis was reported as 46, XY. Sequence analysis of the NR5A1 gene revealed a novel heterozygote c.1075_1089del (p.Leu359_Leu363del) variant. The patient was raised as a female and oestrogen replacement was started following gonadectomy. Conclusion. It should be kept in mind that virilization may develop at puberty in individuals with 46, XY disorder of sexual development due to NR5A1 mutation.

Genome Wide Association Studies (GWAS) are excellent opportunities to define culprit genes in complex disorders such as the polycystic ovary syndrome (PCOS). PCOS is a prevalent disorder characterized by anovulation, hyperandrogenism and polycystic ovaries, which benefitted from several GWASs in Asians and Europeans revealing more than 20 potential culprit genes near associated single nucleotide variations (SNV). Translation of these findings into the clinical practice raises difficulties since positive hits are surrogate SNVs linked with causative mutations by linkage disequilibrium (LD). Studies in Mediterranean populations (e.g. Southern Europe and North Africa) raise supplementary problems because of a different LD-pattern, which may disrupt the link with causative mutations. Our experience in MEDIGENE program between Tunisia and France enforces the necessity of genetic anthropology studies before translating GWAS data. Tunisians are a heterogeneous population with ancestral Berbers, European, Arab and Sub-Saharan African components while South Europeans display a high level of genetic diversity, partially explained by gene flow from North Africa. Human diversity studies require sampling from Middle East and North Africa (MENA) region that will help to understand genetic factors in complex diseases.

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.

Acromegaly is associated with increased mortality and decreased life expectancy. Cardiovascular disease is the principal cause of premature mortality in patients with acromegaly, accounting for about 60% of deaths. GH and/or IGF-I exert direct cardiac effects: enhance cardiac contractility, stimulate cardiomyocyte growth, influence calcium influx in cardiomyocytes. Cardiac remodelling is influenced by hypertension and insulin resistance. Among cardiovascular risk factors arterial hypertension, reported in 35% of patients with acromegaly, ranks among most important negative prognostic factors for mortality. Hypertension plays significant role in the development of cardiac hypertrophy, especially in older acromegalic patients and diastolic blood pressure is best predictive factor for cardiac hypertrophy. Therefore, early and aggressive hypertension treatment is essential for prognosis in acromegaly. Other important risk factors are: valvular defects, arrhythmias, endothelial dysfunction, heart failure, lipid abnormalities and coronary artery disease. Numerous studies suggest that patients with acromegaly are under threat of arrhythmias, especially those with structural heart abnormalities. Congestive heart failure as end-stage acromegalic cardiomyopathy occurs usually in older patients, with long-term uncontrolled disease and other cardiovascular and metabolic complications. Relation between acromegaly and coronary artery disease is controversial as it seems to be connected rather with classical cardiovascular risk factors than GH and IGF-1 overexpresion.

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.

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.

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.