ESPE Abstracts

Primary adrenal insufficiency (PAI) is an important diagnosis to make as it is potentially life-threatening and requires urgent treatment. Although most paediatric endocrinologists have experience of more common conditions such as congenital adrenal hyperplasia (CAH) and autoimmune adrenal insufficiency, more than 30 other genetics causes of PAI exist, as well as physical causes such as haemorrhage. Reaching a specific diagnosis for some of these rarer conditions can have impo...

Congenital adrenal insufficiency is a potentially life-threatening condition that can present soon after birth in many different ways. The classic presentation is a salt-losing crisis due to mineralocorticoid insufficiency, often between a week and two of life, but babies with predominant glucocorticoid insufficiency can present with other features such as prolonged jaundice, hypoglycaemia and hyperpigmentation. Most children with congenital adrenal insufficiency present to em...

Steroidogenic factor-1 (SF-1, NR5A1) is a key regulator of adrenal and gonad development, and controls transcription of many genes in these endocrine axes. A role for SF-1/NR5A1 in human endocrine conditions was first established 15 years ago when rare individuals with adrenal hypoplasia and 46,XY DSD (testicular dysgenesis, Müllerian structures) were reported. Although it was felt that adrenal failure would be a key feature of SF-1 disruption, in the pa...

Background: Steroidogenic factor 1 (SF1), encoded by the gene NR5A1, is a member of the orphan nuclear receptor superfamily and important regulator of gonadal and adrenal function. Variations in SF1 lead to a spectrum of conditions including 46,XY DSD, hypospadias, adrenal insufficiency, male factor infertility, and primary ovarian insufficiency. Inheritance patterns can be complicated (e.g. de novo dominant, sex-limited dominant, and autosomal recessive). In...

The genomic analysis of 46,XX individuals with testes (known as testicular Disorders/Differences of Sex Development (TDSD) or ovotestes (ovotesticular DSD (OTDSD)) supports the hypothesis that ‘pro-testis/anti-ovary’ or ‘pro-ovary/anti-testis’ genetic pathways exist. These children typically present with virilized genitalia due to testosterone production from the presence of testicular tissue. Many individuals with TDSD and a minority with OTDSD have a tran...

Background: The adrenal glands and gonads develop from an area of intermediate mesoderm between 6 and 10 weeks post conception (wpc) in humans. Elucidating the genomic components and pathways in these processes could reveal novel aspects of human developmental biology and new factors implicated in adrenal insufficiency and DSD.Objective and hypotheses: To develop a unique genomic atlas of adrenal and gonad development during critical stages of human embr...

Background: CYP11A1 gene encodes the cholesterol side-chain cleavage enzyme, P450scc, which plays a key role in the initial steps of steroidogenesis. CYP11A1 insufficiency lead to a variable phenotype ranging from severe early onset primary adrenal insufficiency (PAI) in the neonatal period,with 46,XY DSD; to late-onset PAI with normal genitalia.Objective: Detail the phenotype of a family sharing newly described...

Background: We present a patient with co-existence of two rare conditions 3β-Hydroxysteroid dehydrogenase type 2 deficiency (HSD3B2) the rarest form of Congenital Adrenal Hyperplasia (CAH) and Bartter’s Syndrome (hypokalaemic alkalosis secondary to hyperaldosteronism).Case Report: A female infant (46XX) born at 34/40 weeks weighing 2.67 kg to non-consanguineous parents presented on day four of life with significant weight loss. Subsequent inves...

Background: When a baby presents with atypical genitalia, the most important diagnosis to consider is 21-hydroxylase deficiency (21OHD, CAH, 46,XX). However, primary adrenal insufficiency (PAI) can also occur in 46,XY children with differences in sex development (DSD), although this is less common. Known causes of 46,XY DSD-PAI include high blocks in steroidogenesis (STAR, CYP11A1); steroidogenic enzyme defects (HSD3B2, CYP17A1</...

Background: Recurrent miscarriage (RM) is traditionally described as three or more consecutive pregnancy losses and remains a challenging condition, affecting 1-3% of couples trying to conceive. Although factors such as uterine abnormalities, maternal hypothyroidism and parental balanced translocations are associated with RM, in most situations the aetiology is unknown. The coexistence of RM and live births in many families suggests a potential association wit...