ESPE Abstracts

Introduction: 21-Hydroxylase deficiency (21OHD) is the most common form of congenital adrenal hyperplasia (CAH). Clinical and laboratory findings vary depending on the enzyme activity.Case Report 1: A 2-month-old male infant referred as hypospadias. He was born at term from consanguineous parents with intrauterine growth retardation. The mother had no problem during pregnancy. The external genitalia had penoscrotal hypospadias with chordee and both teste...

Background: In humans, loss-of-function mutations in Nicotinamide nucleotide transhydrogenase (NNT) cause familial glucocorticoid deficiency, a potentially fatal, adrenal-specific disorder characterized by increased ACTH and reduced cortisol levels. NNT is a highly conserved inner mitochondrial membrane protein, which supplies high concentrations of NADPH for detoxification of reactive oxygen species (ROS) by glutathione and thioredoxin pathways.<p class="abstext"...

Background: P450 oxidoreductase deficiency (PORD) is characterised by glucocorticoid and sex steroid deficiency and skeletal malformations, resembling Antley–Bixler syndrome (ABS, MIM 124015), a skeletal malformaton phenotype also present in patients with fibroblast growth factor receptor 2 mutations (FGFR2, MIM 176943). While genetic testing confirms both conditions, establishing the exact diagnosis on clinical grounds can be challenging.Objective ...

Background: Early onset of androgen excess in pre-pubertal children is usually caused by called premature adrenarche (PA). PA is characterised by the development of pubic and axillary hair, adult-type body odour in girls <8yrs and in boys <9yrs. PA may be a forerunner condition of polycystic ovary syndrome (PCOS), a complex metabolic disorder also characterised by androgen excess. Women with PCOS have higher risk of developing type 2 diabetes, dyslipidae...

Background: Previous descriptions of the steroidogenic capacity of human foetal adrenal glands in an ex vivo culture system focused on the classic androgen pathway and the alternative DHT pathway. However, no information is available on the abundance and role of the adrenal-derived 11-oxygenated androgens during foetal development, and how their levels correlate to classic androgens.Aim: To characterise the ster...

Introduction: Early-onset androgen excess commonly presents in pre-pubertal girls as premature adrenarche (PA). Girls with PA have clinical signs of androgen excess, such as pubic/axillary hair, body odour, greasy hair, and moderately elevated adrenal androgens before their 8th birthday. There is conflicting evidence if girls with PA are at higher risk to have or develop metabolic dysfunction, or progress to developing Polycystic Ovary Syndrome (PCO...

Background: Management of patients with CAH remains challenging. There is increasing evidence to suggest that failure to optimize treatment during childhood not only affects final height but also leads to psychological and psychiatric problems. Previous qualitative structural T2-weighted MRI studies have identified white matter hyper-intensities in up to 46% of CAH patients. The nature and functional relevance of these abnormalities remains unknown.Objec...

Background: P450 oxidoreductase (POR) is a co-factor critical for the function of type 2 microsomal cytochrome P450 enzymes. POR deficiency (PORD) results in a rare form of congenital adrenal hyperplasia, with combined attenuation of CYP21A2 and CYP17A1 steroidogenic enzymes. It is characterised by combined deficiencies of glucocorticoids and androgens postnatally. Differences in sex development can arise in both sexes due to antenatal activation of the altern...

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: Androgen excess in childhood is a common clinical presentation and might signify serious pathology. We have recently explored patterns and severity of androgen excess in a large female adult cohort to differentiate common polycystic ovarian syndrome (PCOS) from non-PCOS pathology, including congenital adrenal hyperplasia (CAH), ovarian hyperthecosis and adrenal and ovarian tumours (Elhassan et al., JCE&M 2018). Herein, we undertake a similar approach f...