Congenital adrenal hyperplasia (CAH)
Concise summary
CAH is an autosomal recessive group of disorders of adrenal steroidogenesis; >90% of cases are due to 21‑hydroxylase (CYP21A2) deficiency. Enzyme defects cause cortisol deficiency with variable aldosterone deficiency and androgen excess.
Presentation ranges from a neonatal salt‑wasting adrenal crisis to ambiguous genitalia in genetic females or later hyperandrogenic symptoms.
In the emergency setting priorities are prompt recognition, immediate parenteral glucocorticoid, isotonic fluid resuscitation, correction of hypoglycaemia and electrolyte management, and urgent specialist escalation. (NICE NG243; NIPE)
Epidemiology and genetics
- CAH is rare; reported incidence varies between populations and is higher with parental consanguinity.
- Inheritance is autosomal recessive.
- The commonest cause is 21‑hydroxylase deficiency (>90%). 11β‑hydroxylase deficiency is the next most frequent cause.
- The gene for 21‑hydroxylase is CYP21A2 on chromosome 6p21 (near the HLA complex).
Pathophysiology
- 21‑hydroxylase is required for cortisol and aldosterone synthesis; deficiency causes decreased cortisol with loss of negative feedback, leading to increased ACTH and adrenal hyperplasia.
- Accumulation of steroid precursors (notably 17‑hydroxyprogesterone) is shunted into androgen synthesis, producing androgen excess and virilisation.
- If aldosterone is deficient (salt‑wasting forms) there is sodium loss, hyperkalaemia, dehydration, hypotension and risk of adrenal crisis.