ACTA ENDOCRINOLOGICA (BUC)

Context. Radioactivity has been known to be a causative factor for thyroid cancer. Objective. To answer whether the Chernobyl nuclear accident had any harmful effect on the rate of thyroid cancers after a wait-and-see period. Background. The Chernobyl accident in 1986 was chosen as a milestone because of its close proximity to the geographical area studied. Design. The time periods chosen were: I. 1990-1996 (latent period), II. 1997-2003 (sensitive period), III. 2004-2015 (control period). Subject and Methods. A retrospective study was conducted in a teaching and reference state hospital. The statistical analysis of the data of 4251 patients was made by chi-square and Fisher exact tests. Results. A total of 4251 patients were operated on because of thyroid diseases between 1990-2015. The number of patients in regard to the three time periods were 817, 1141 and 2293, respectively. Statistically significant rise of thyroid cancer and significant geographic vulnerability among different parts of the country were detected between the first two periods, but not between the second and third. The rising rates of malignancy were 1.71% (14/817), 6.83% (78/1141) and 8.59%(197/2293). The mean ages of malignant cases were 51.07 years, 46.2 years and 41.8 years although the mean ages of benign cases were 47.91,60.2, and 61.3 years according to groups, respectively. Conclusion. The Chernobyl nuclear accident seemed to have harmful effect on the rate of thyroid cancer or at least contributed to its increase.

Cushing syndrome in the paediatric age group is very difficult to diagnose due to atypical presenting features in children. Primary pigmented nodular adrenocortical disease (PPNAD) is a rare cause of ACTH-independent Cushing syndrome in children and it has characteristic gross and microscopic pathologic features. We report a case of PPNAD in a 16-year-old boy who was evaluated in our hospital with chief complaints of poor height velocity and rapid weight gain for 2-3 years before presentation. Proper evaluation showed ACTH-independent Cushing syndrome with normal imaging. Total bilateral adrenalectomy was performed followed by hormones replacement. 6 months after surgery, significant acceleration of height velocity was noticed. Patient also lost body weight and developed secondary sexual characteristics.

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. The aim of this experimental study was to examine the effect of erythropoietin (Epo) on rat model and particularly in an ischemia-reperfusion (IR) protocol. The beneficial effect or non-effectiveness of that molecule were studied haematologically using blood mean corpuscular hemoglobin levels (MCH). Materials and methods. Forty rats of mean weight 247.7 g were used in the study. MCH levels were measured at these time points: on 60 min after reperfusion (groups A and C), and on 120 min after reperfusion (groups B and D). C and D groups were administered by Epo. Results. Epo administration nonsignificantly increased the MCH levels by 0.19 pg [-0.34 pg - 0.72 pg] (P= 0.4762). This finding was in accordance with the results of paired t-test (P= 0.3827). Reperfusion time non-significantly increased the MCH levels by 0.02 pg [-0.51 pg - 0.55 pg] (P= 0.9404), also in accordance with paired t-test (P= 0.9049). However, Epo administration and reperfusion time together produced a nonsignificant combined effect in decreasing the MCH levels by 0.13 pg [-0.18 pg - 0.45 pg] (P= 0.4087). Conclusion. Results of this study indicate that Epo administration, even in short-term prospect of 2 hours reperfusion, starts reversing ischemic damages. These results are also reinforced by predicted MCH values adjusted for weight. However, the significant effect needs more than 2 hours in order to appear.

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.

No inheritance of early-onset female-related type 2 diabetes was reported within Chinese families. In this study, we aim to describe the inheritance pattern of type 2 diabetes in a 3-generation family and identify the gene responsible for type 2 diabetes. Genome-wide multipoint parametric linkage analysis revealed a maximum multipoint logarithm of odds (lod) score of 2.1 for a locus being associated with type 2 diabetes in this family on chromosome 20p11.2-12 between 23.5~30.8cM. Type 2 diabetes may be transmitted as an autosomal dominant trait with a high female-related penetrance in this family. Here we describe the first genetic locus for type 2 diabetes at chromosome 20p11.2-12. This region contains 8 known or predicted genes (PLCB1, PLCB4, LAMP5, PAK7, ANKEF1, SNAP25, SLX4IP, and JAG1). Gene SNAP25 which linked to energy or glucose homeostasis associated phenotypes may play a role in the development of type 2 diabetes in this family.

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.