Endocrine Abstracts

The human adrenal gland develops from around 4 weeks gestation and undergoes distinct changes throughout pre- and post-natal life. Defects in these processes can cause adrenal hypoplasia and result in adrenal insufficiency. Adrenal hypoplasia can be: i) secondary to abnormal pituitary function, ACTH synthesis or splicing; ii) the result of ACTH resistance (familial glucocorticoid deficiency; triple A syndrome); or iii) due to a primary defect in adrenal development itself (primary adrenal hypoplasia). Most causes of primary adrenal hypoplasia are X-linked and due to changes in the nuclear receptor DAX-1. Boys typically have salt-losing adrenal failure in early infancy or childhood and hypogonadotropic hypogonadism (HH) and impaired spermatogenesis in adolescence. Alternative presentations have now been reported including early puberty or adult-onset adrenal insufficiency. The molecular aetiology of X-linked AHC remains poorly understood as DAX-1 paradoxically represses transcription. However, transcriptional activation by DAX-1 may occur and adrenal stem cell development may be dysregulated. Other forms of primary adrenal hypoplasia may be due to defects in steroidogenic factor-1 (SF-1) or WNT4. In this session we will obtain insight into new aspects of adrenal development and function throughout the early lifespan; review some of the molecular causes of adrenal hypoplasia; and discuss the importance of these diagnoses for the paediatric endocrinologist.