ESPE Abstracts

Background: Biochemical ratios of precursor-to-product urinary steroid metabolites have been proposed as surrogate markers of steroidogenic enzyme activity to aid the differential diagnosis of inborn disorders of steroidogenesis. Using ratios rather than total amounts facilitates analysis of single spot urine samples, more convenient than 24-h urine collections for young children. Previous studies examining the utility of these biochemical ratios have been lim...

Background: Protein intake is crucial for growth. Many inherited metabolic diseases (IMD) require a strict controlled protein diet.Aim: to evaluate growth, pubertal status and body composition in IMD requiring a strict controlled protein diet.Patients & Méthods: Longitudinal follow up cohort study. We recorded data before 4years (early childhood, n=189); betwe...

Background: Hypospadias in boys may be associated with a lack of androgen exposure during the masculinisation programming window. As testosterone has effects on the vasculature, we assessed whether boys with hypospadias show any evidence of vascular dysfunction.Methods: Excess foreskin tissue was obtained from boys undergoing hypospadias repair (cases) or circumcision (controls) and small arteries dissected from this tissue. Vascular contractility was as...

Background: FOP is an ultra-rare, severely disabling genetic disorder characterised by progressive heterotopic ossification (HO) following flare-ups. The median age at diagnosis is 5 years, and patients are managed by multiple specialties. No study to date has provided a longitudinal evaluation of FOP. Final data are presented for participants, aged <25 years, enrolled in the first 36-month, prospective, global natural history study of FOP (NCT02322255).</...

Background: Combinations of follicle-stimulating hormone (FSH) and human chorionic gonadotropin (hCG) have been successful in treating males with hypogonadotropic hypogonadism (HH). The aim of this study was to investigate the efficacy and safety of corifollitropin alfa (CFA), a long-acting FSH analog, combined with hCG to induce testicular growth and pubertal development in adolescent males with HH.Methods: This was a 6...

Background: Primary ovarian insufficiency (POI) affects 1% of women and is associated with significant medical consequences. In approximately 10% of cases, POI presents early with absent puberty or primary amenorrhoea. A genetic cause for POI can be found in up to 30% of women. Identified genes often relate to the complex biological processes occurring in fetal life which underpin normal ovary development and function in later adulthood.Objective: We aim...

Background: Initiation and progression of puberty requires concerted action of activating and inhibiting factors. Recently, cases of central precocious puberty have been linked to loss-of-function mutations of makorin RING-finger protein 3 (MKRN3) indicating a pivotal inhibitory role of MKRN3 on GnRH secretion.Objective and hypotheses: To investigate peripubertal circulating MKRN3 levels in healthy boys.Method: Healthy boys (n<...

Introduction: Orthodenticle homeobox 2 (OTX2) is a transcription factor that plays a critical role in brain and eye development. Heterozygous deleterious mutations in this gene lead to eye malformation such as anophthalmia, microphthalmia, coloboma or optic nerve hypoplasia, normal or hypoplastic pituitary gland and normal or ectopic posterior pituitary gland with isolated growth hormone deficiency or combined pituitary hormone deficiency. There is no...

A broad spectrum of human diseases, including abnormalities in steroidogenesis, are caused by mutations in the NADPH cytochrome P450 oxidoreductase (POR) (1-4). Human POR is a diflavin reductase that transfers electrons from NADPH to small molecules, non-P450 redox partners and cytochrome P450 proteins in the endoplasmic reticulum. Cytochrome P450 proteins perform a very wide range of reactions, including metabolism of steroids, drugs and other xenobiotics. Therefore, genetic ...

Background: Tissue sensitivity to glucocorticoids is characterized by significant inter-individual variation in terms of therapeutic response and susceptibility to several stress-related disorders. Proteomics approaches, combined with appropriate bioinformatics analysis, offer a comprehensive description of molecular phenotypes with clear links to human disease pathophysiology.Objective and Hypotheses: To investigate the usefulness of pl...