Autoimmune thyroiditis is more frequent in females, and increases in frequency over age during childhood and adolescence. At the time of diagnosis, frequency of overt and subclinical hypothyroidism is similar to that of euthyroid goiter.

The present study was performed to determine the prevalence of metabolic syndrome (MS) and its risk factors in obese children and adolescents. The study included 352 obese children and adolescents (body mass index [BMI] > or = 95th percentile) aged between 2 and 19 years. The diagnosis of MS was made according to the criteria adapted from the World Health Organization (WHO) and the National Cholesterol Education Program Adult Treatment Panel III (NCEP ATP III) guidelines. BMI z-scores were calculated to assess the degree of obesity. The prevalence of MS and risk factors were determined. Determinants of MS were examined using regression analysis. The prevalence of MS was 41.8%. The age at onset of obesity, sedentary life-span, fasting blood levels of glucose, insulin, triglyceride, very-low-density lipoprotein (VLDL) cholesterol, and alanine aminotransferase (ALT) were higher, while levels of high-density lipoprotein (HDL) cholesterol and the number of actively spent hours were lower in cases with MS (p < 0.05). The most important determinant of MS was BMI z-score (r = 0.31, p < 0.0001). A one-point increase in BMI z-score yielded a 2-fold increase in the prevalence of MS. The prevalence of MS increased from 27.6% to 60.7% when the BMI z-score increased from 2.3 to 3.3. The risk of developing MS was 2.6-fold higher in cases with BMI z-score > 3 when compared to those with z-scores between 2 and 3. The results from this study indicate that, although the correlation between MS and the BMI z-score was weak, the BMI z-score may be an effective parameter in identifying obese children and adolescents at risk for MS. Screening the cases with BMI z-scores > or = 2 for MS is important for establishing an early diagnosis.

Congenital adrenal hyperplasia (CAH), resulting from mutations in CYP11B1, a gene encoding 11β-hydroxylase, represents a rare autosomal recessive Mendelian disorder of aberrant sex steroid production. Unlike CAH caused by 21-hydroxylase deficiency, the disease is far more common in the Middle East and North Africa, where consanguinity is common often resulting in identical mutations. Clinically, affected female newborns are profoundly virilized (Prader score of 4/5), and both genders display significantly advanced bone ages and are oftentimes hypertensive. We find that 11-deoxycortisol, not frequently measured, is the most robust biochemical marker for diagnosing 11β-hydroxylase deficiency. Finally, computational modeling of 25 missense mutations of CYP11B1 revealed that specific modifications in the heme-binding (R374W and R448C) or substrate-binding (W116C) site of 11β-hydroxylase, or alterations in its stability (L299P and G267S), may predict severe disease. Thus, we report clinical, genetic, hormonal, and structural effects of CYP11B1 gene mutations in the largest international cohort of 108 patients with steroid 11β-hydroxylase deficiency CAH.steroid hormones | missense mutations | classic CAH | ambiguous genitalia C ongenital adrenal hyperplasia (CAH) is a Mendelian disorder transmitted as an autosomal recessive trait. The most prevalent form of CAH arises from steroid 21-hydroxylase enzyme deficiency, accounting for ∼90-95% of all cases (1, 2). In contrast, CAH caused by steroid 11β-hydroxylase deficiency is considerably rare, with a prevalence of 5-8% (3), from which we estimate an overall frequency of 1 in 100,000 live births.Two homologous enzymes, 11β-hydroxylase and aldosterone synthase, are encoded by the CYP11B1 and CYP11B2 genes, respectively. The two genes are 40-kb apart, each comprising nine exons and mapped to chromosome 8q21-22 (3, 4) (Fig. 1A). In contrast to CYP21A2 and its CYP21A1P pseudogene, CYP11B1 and CYP11B2 are both active and do not have a pseudogene. The two encoded homologs, however, have distinct functions in cortisol and aldosterone synthesis, respectively (3). In the zona fasciculata, 11β-hydroxylase converts 11-deoxycortisol and 11-deoxycorticosterone to cortisol and corticosterone, respectively, and is regulated by adrenocorticotropic hormone secreted by the pituitary. In contrast, in the zona glomerulosa aldosterone synthase converts corticosterone to aldosterone with the intermediate production of 18-hydroxycorticosterone. These latter conversions are controlled mainly by the renin angiotensin II system and serum potassium concentration (3).Deficiency of 11β-hydroxylase prevents the conversion of 11-deoxycortisol to cortisol and 11-deoxycorticosterone to corticosterone. This results in high levels of 11-deoxycortisol and 11-deoxycorticosterone, respectively, which are shunted into the androgen synthesis pathway, resulting in high levels of the androgenic steroid, androstenedione. Female newborns are thus profoundly virilized and exhibit significant masculinization of the ex...

Sulfonylurea receptors (SURx) are required subunits of the ATP-sensitive potassium channel. SURx alone is electrophysiologically inert. However, when SURx is combined with an inward rectifier Kir6.2 subunit, ATPsensitive potassium channel activity is generated. We report the identification, characterization, and localization of Dsur, a novel Drosophila gene that is highly related to the vertebrate SUR family. The Dsur coding sequence contains structural features characteristic of the ABC transporter family and, in addition, harbors 1.7 kilobases of a distinctive sequence that does not share homology with any known gene. When Dsur alone is expressed in Xenopus oocytes glibenclamide-sensitive potassium channel activity occurs. During Drosophila embryogenesis, the Dsur gene is specifically expressed in the developing tracheal system and dorsal vessel. Studies of the Drosophila genome support that only a single Dsur gene is present. Our data reveal conservation of glibenclamide-sensitive potassium channels in Drosophila and suggest that Dsur may play an important role during Drosophila embryogenesis. The lack of gene duplication in the Drosophila system provides a unique opportunity for functional studies of SUR using a genetic approach.

Objective: Gonadotropin stimulation test is the gold standard to document precocious puberty. However, the test is costly, time-consuming and uncomfortable. The aim of this study was to simplify the intravenous gonadotropin-releasing hormone (GnRH) stimulation test in the diagnosis of precocious puberty and in the assessment of pubertal suppression. Methods: Data pertaining to 584 GnRH stimulation tests (314 testsfor diagnosis and 270 for assessment of pubertal suppression) were analyzed. Results: Forty-minute post-injection samples had the greatest frequency of “peaking luteinizing hormone (LH)” (p<0.001) in the diagnostic tests when the cut-off value was taken as 5 IU/L for LH, 40th minute sample was found to have 98% sensitivity and 100% specificity in the diagnosis of precocious puberty, while the sensitivity and specificity of the 20th minute sample was 100% in the assessment of pubertal suppression. Conclusion: LH level at the 40th minute post-injection in the diagnosis of central precocious puberty and at the 20th minute post-injection in the assessment of pubertal suppression is highly sensitive and specific. A single sample at these time points can be used in the diagnosis of early puberty and in the assessment of pubertal suppression. Conflict of interest:None declared.

Background/Aims: There are few studies in the literature that have evaluated the etiological factors in boys with central precocious puberty (CPP), and these studies are limited in terms of the sample size. In the present study, we aimed to evaluate the etiological factors in male CPP cases. Methods: One hundred male CPP subjects, aged between 9 months and 10.5 years, were included. The medical records were screened, and age at diagnosis, bone age, body weight, height, pubertal stage, imaging findings of the pituitary gland, testosterone, and basal and stimulated gonadotropin levels were recorded. Results: There was no underlying cause in 74% of the cases, and an organic cause was determined in only 26%. Most of the organic cases had been diagnosed before the age of 7 years, whereas most of the idiopathic cases had been diagnosed after the age of 7 years. Conclusion: An organic cause was determined in 26% of the male patients with CPP. This rate is one of the lowest rates in the literature and indicates that the number of idiopathic male CPP cases is increasing over time. When a boy is diagnosed with CPP above the age of 7 years, the odds of detecting an underlying pathology are very low, and these cases are mostly idiopathic.

Objective: This study aimed (a) to investigate the relationship between the degree of obesity and serum adiponectin, tumor necrosis factor (TNF)−α, leptin, insulin levels and the lipid profile; (b) to clarify the relationship between insulin resistance/glucose tolerance and adipocytokine levels; and (c) to investigate the value of adipocytokine levels as a marker of metabolic syndrome (MS).Methods: We studied 151 obese children and adolescents (86 boys and 65 girls; mean age was 12.3±2.4 years). We defined obesity as a body−mass index (BMI) z−score more than 2 SD above the mean for age and sex. The control group consisted of 100 children (48 boys, 52 girls, mean age 12.4±2.5 years). Fasting glucose, insulin levels and lipid profiles were measured in all cases and controls after a 12−hour fast. Adiponectin, TNF−α, and leptin levels were measured in the subjects who participated in the adipocytokine branch of the study. An oral glucose tolerance test (OGTT) was also performed in all obese patients. Obese patients were grouped into three subgroups according to their glucose tolerance and insulin sensitivity assessment, and also according to whether they were grouped as MS or not.Results: Serum levels of total cholesterol, LDL and VLDL cholesterol, log triglyceride, insulin, leptin and TNF−α were higher, whereas HDL and square root adiponectin levels were lower in the obese group when compared with controls. Multiple regression analysis among BMI−z score, LDL, triglyceride, HOMA−IR, leptin and TNF−α as determinants of adiponectin revealed that BMI−z score was the only determinant for adiponectin (r:−0.45, p<0.0001). Adiponectin levels in hyperinsulinemic and impaired glucose tolerance groups (IGT) tended to be lower than in normoinsulinemic obese children, however, the difference was not significant. There was a weak negative correlation between adiponectin levels and increasing severity of insulin resistance (r=−0.23, p=0.005) in the groups of obese subjects. Mean serum adiponectin level in subjects with MS was lower than in subjects without MS (p=0.008).Conflict of interest:None declared.

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