Correction: Congenital adrenal hyperplasia due to 11-beta-hydroxylase deficiency: functional consequences of four CYP11B1 mutations.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Gonadotropin- and Adrenocorticotropic Hormone-Independent Precocious Puberty of Gonadal Origin in a Patient with Adrenal Hypoplasia Congenita Due to DAX1 Gene Mutation - A Case Report and Review of the Literature: Implications for the Pathomechanism.

Background/aims: Mutations in the DAX1 gene cause X-linked adrenal hypoplasia congenita (AHC) classically associated with hypogonadotropic hypogonadism. Unexpectedly, precocious puberty (PP) has been reported in some cases, its mechanism remaining unclear.

Methods: We longitudinally studied a boy with AHC due to DAX1 gene mutation who developed peripheral PP at age 4.

Blood Pressure in a Large Cohort of Children and Adolescents With Classic Adrenal Hyperplasia (CAH) Due to 21-Hydroxylase Deficiency.

Background: Data on blood pressure (BP) in children and adolescents with classic congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency are conflicting in the literature.

Patients And Methods: BP data of n = 716 children and adolescents (aged 3-18 years) from a national CAH database were analyzed. BP data were adjusted for height and compared to contemporary national reference data.

Adrenal and Ovarian Phenotype of a Tissue-Specific Urocortin 2-Overexpressing Mouse Model.

Urocortin 2 (UCN2) is a neuropeptide of the CRH family, involved in homeostatic mechanisms, the stress response, and control of anxiety. To elucidate the effects of UCN2 on steroidogenesis, we developed a mouse model that allows a Cre recombinase-determined conditional overexpression of UCN2 (UCN2-COE). In these mice SF1-Cre-driven overexpression of UCN2 was restricted to the adrenal glands, gonads, and parts of the hypothalamus.

In vivo investigations of the effect of short- and long-term recombinant growth hormone treatment on DNA-methylation in humans.

Treatment with recombinant human growth hormone (rhGH) has been consistently reported to induce transcriptional changes in various human tissues including peripheral blood. For other hormones it has been shown that the induction of such transcriptional effects is conferred or at least accompanied by DNA-methylation changes. To analyse effects of short term rhGH treatment on the DNA-methylome we investigated a total of 24 patients at baseline and after 4-day rhGH stimulation.

46,XY disorder of sex development in a sudanese patient caused by a novel mutation in the HSD17B3 gene.

In this study, we present a Sudanese 46,XY patient raised as a female and diagnosed at the age of 20 years with having 17β-hydroxysteroid dehydrogenase type 3 (17β-HSD3) deficiency. She presented with primary amenorrhea, undeveloped breasts and a male pattern of secondary sexual characteristics. Examination of her external genitalia showed type IV genital circumcision.

Characterisation of three novel CYP11B1 mutations in classic and non-classic 11β-hydroxylase deficiency.

Background: Congenital adrenal hyperplasia (CAH) is one of the most common autosomal recessive inherited endocrine diseases. Steroid 11β-hydroxylase (P450c11) deficiency (11OHD) is the second most common form of CAH.

Aim: The aim of the study was to study the functional consequences of three novel CYP11B1 gene mutations (p.

Androgen receptor function links human sexual dimorphism to DNA methylation.

Sex differences are well known to be determinants of development, health and disease. Epigenetic mechanisms are also known to differ between men and women through X-inactivation in females. We hypothesized that epigenetic sex differences may also result from sex hormone functions, in particular from long-lasting androgen programming.

Congenital adrenal hyperplasia due to 11-beta-hydroxylase deficiency: functional consequences of four CYP11B1 mutations.

Congenital adrenal hyperplasia (CAH) is one of the most common autosomal recessive inherited endocrine disease. Steroid 11β-hydroxylase deficiency (11β-OHD) is the second most common form of CAH. The aim of the study was to study the functional consequences of three novel and one previously described CYP11B1 gene mutations (p.

The novel mutation p.Trp147Arg of the steroidogenic acute regulatory protein causes classic lipoid congenital adrenal hyperplasia with adrenal insufficiency and 46,XY disorder of sex development.

Background: The steroidogenic acute regulatory protein (StAR) is essential for steroidogenesis by mediating cholesterol transfer into mitochondria. Inactivating StAR mutations cause lipoid congenital adrenal hyperplasia.

Objective And Methods: To identify causative mutations in a patient presenting with adrenal failure during early infancy.

Steroid hormone profiles in prepubertal obese children before and after weight loss.

Context: Little information is available on the steroid hormone profiles in obese children and their changes after weight loss.

Objective: We compared liquid chromatography-tandem mass spectrometry of serum steroid hormone profiles between obese and normal-weight children and studied the differential effects of weight loss on these hormones.

Design: This study was a cross-sectional comparison between obese and normal-weight children and a longitudinal 1-year follow-up study during lifestyle intervention in obese children.

Five novel mutations in the SCNN1A gene causing autosomal recessive pseudohypoaldosteronism type 1.

Background: Pseudohypoaldosteronism type 1 (PHA1) is a monogenic disease caused by mutations in the genes encoding the human mineralocorticoid receptor (MR) or the α (SCNN1A), β (SCNN1B) or γ (SCNN1G) subunit of the epithelial Na(+) channel (ENaC). While autosomal dominant mutation of the MR cause renal PHA1, autosomal recessive mutations of the ENaC lead to systemic PHA1. In the latter, affected children suffer from neonatal onset of multi-organ salt loss and often exhibit cystic fibrosis-like pulmonary symptoms.

Predicting the optimal basal insulin infusion pattern in children and adolescents on insulin pumps.

Objective: We aimed at developing and cross-validating a mathematical prediction model for an optimal basal insulin infusion pattern for children with type 1 diabetes on continuous subcutaneous insulin infusion therapy (CSII).

Research Design And Methods: We used the German/Austrian DPV-Wiss database for quality control and scientific surveys in pediatric diabetology and retrieved all CSII patients <20 years of age (November 2009). A total of 1,248 individuals from our previous study were excluded (dataset 1), resulting in 6,063 CSII patients (dataset 2) (mean age 10.

Pseudohypoaldosteronism.

Pseudohypoaldosteronism (PHA) is a rare syndrome of mineralocorticoid resistance. PHA type 1 (PHA1) can be divided into two different forms, showing either a systemic or a renal form of mineralocorticoid resistance. The first is caused by mutations of the genes coding the epithelial sodium channel, the latter is caused by mutations in the mineralocorticoid receptor coding gene NR3C2.

Implementation of a liquid chromatography tandem mass spectrometry assay for eight adrenal C-21 steroids and pediatric reference data.

Background: Sensitive and accurate determination of steroids is essential for diagnosing congenital and acquired adrenal diseases. Since plasma concentrations change during childhood, age-specific reference ranges are the prerequisite for clinical interpretation. The objectives of this study were to develop a sensitive and reliable method for simultaneous detection and quantification of progesterone, 17-hydroxyprogesterone, deoxycorticosterone (DOC), 11-deoxycortisol, 21-deoxycortisol, corticosterone, cortisol (F) and cortisone (E) by ultra-performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS) and to establish age- and sex-specific reference ranges from birth to adulthood.

Frequency and characterization of DNA methylation defects in children born SGA.

Various genes located at imprinted loci and regulated by epigenetic mechanisms are involved in the control of growth and differentiation. The broad phenotypic variability of imprinting disorders suggests that individuals with inborn errors of imprinting might remain undetected among patients born small for gestational age (SGA). We evaluated quantitative DNA methylation analysis at differentially methylated regions (DMRs) of 10 imprinted loci (PLAGL1, IGF2R DMR2, GRB10, H19 DMR, IGF2, MEG3, NDN, SNRPN, NESP, NESPAS) by bisulphite pyrosequencing in 98 patients born SGA and 50 controls.

Age and skin site related differences in steroid metabolism in male skin point to a key role of sebocytes in cutaneous hormone metabolism.

Hormone concentrations decline with aging. Up to now it was not clear, whether the decrease of hormone concentrations in blood samples are also present in cutaneous suction blister fluids, and whether skin from different anatomical sites shows different hormone concentrations.Analysis of suction blister fluids and paired blood samples from young (mean 27.

Steroid 21-hydroxylase gene mutational spectrum in 50 Tunisian patients: characterization of three novel polymorphisms.

Congenital adrenal hyperplasia (CAH) is an autosomal recessive disease of steroid biosynthesis in humans. More than 90% of all CAH cases are caused by mutations of the 21-hydroxylase gene (CYP21A2), and approximately 75% of the defective CYP21A2 genes are generated through an intergenic recombination with the neighboring CYP21A1P pseudogene. In this study, the CYP21A2 gene was genotyped in 50 patients in Tunisia with the clinical diagnosis of 21-hydroxylase deficiency.

Neonatal screening: identification of children with 11β-hydroxylase deficiency by second-tier testing.

Background: 21-Hydroxylase deficiency (21-OHD) is the target disease of newborn screening for congenital adrenal hyperplasia (CAH). We describe the additional detection of patients suffering from 11β-hydroxylase deficiency (11-OHD) by second-tier testing.

Method: Over a period of 5 years, screening for CAH was done in a total of 986,098 newborns by time-resolved immunoassay (DELFIA®) for 17α-hydroxyprogesterone (17-OHP).

Multiplex ligation-dependent probe amplification analysis of the NR0B1(DAX1) locus enables explanation of phenotypic differences in patients with X-linked congenital adrenal hypoplasia.

Background/aim: X-linked adrenal hypoplasia congenita (AHC) is a rare disorder characterized by primary adrenal insufficiency and hypogonadic hypogonadism. It is caused by deletions or point mutations of the NR0B1 gene, on Xp21. AHC can be associated with glycerol kinase deficiency, Duchenne muscular dystrophy and mental retardation (MR), as part of a contiguous gene deletion syndrome.

Two novel CYP11B1 mutations in congenital adrenal hyperplasia due to steroid 11β hydroxylase deficiency in a Tunisian family.

Steroid 11β hydroxylase deficiency (11β-OHD) (OMIM # 202010) is the second most common form of congenital adrenal hyperplasia (CAH), accounting for 5-8% of all cases. It is an autosomal recessive enzyme defect impairing the biosynthesis of cortisol. The CYP11B1 gene encoding this enzyme is located on chromosome 8q22, approximately 40kb from the highly homologous CYP11B2 gene encoding for the aldosterone synthase.

Transcriptional response of peripheral blood mononuclear cells to recombinant human growth hormone in a routine four-days IGF-I generation test.

Background: There are very few laboratory markers which reflect the biological sensitivity of children to recombinant human growth hormone (rhGH) treatment. Genome-wide transcriptional changes in peripheral blood mononuclear cells (PBMC) have been widely used as functional readout for different pharmacological stimuli.

Objective: To characterize transcriptional changes in PBMC induced by rhGH during a routine short-term IGF-I generation test (IGFGT) in children with growth disorders.