27th May 2025

Aetiology

As an autosomal recessive disorder, CAH most commonly affects the gene encoding 21-hydroxylase (CYP21A2) which is on chromosome 6. The second most common gene affected is that encoding 11-beta-hydroxylase (CYP11B1). As a result of insufficient cortisol production, increased secretion of CRH and ACTH occur, where the latter leads to adrenal hyperplasia and excessive androgen secretion. 

The presentation will vary depending on the severity of mutations present:

• Classical salt-wasting CAH: severe mutations cause females to have virilised atypical genitalia, and severe mineralocorticoid and glucocorticoid deficiency. These can result in salt-wasting crises and adrenal crises respectively.
• Classical simple virilising CAH: moderate mutations result in virilisation, but the ability to retain salt is preserved.
• Non-classical CAH: mild to moderate mutations result in signs of hyperandrogenism but no virilisation of genitalia.