Congenital adrenal hyperplasia is caused by a congenital deficiency of the 21-hydroxylase enzyme. This causes underproduction of cortisol and aldosterone and overproduction of androgens from birth.

It is a genetic condition that is inherited in an autosomal recessive  pattern. In a small number of cases it is caused by a deficiency of 11-beta-hydroxylase  rather than 21-hydroxylase.

Adrenal gland physiology

Aetiology

The most common deficiency in CAH is a 21-hydroxylase deficiency (>90% of CAH cases). 2 types:

• Classic (infants or children) - defect on Ch6
  • Salt losing form - ALDOSTERONE and CORTISOL deficiency
  • Non-salt losing (simple virilizing form) - CORTISOL deficiency
• Non-classic (milder, presents later in adolescence or young adulthood)
• In both forms there are excess ANDROGENS

Pathophysiology

21 hydroxylase deficiency:

• 21-hydroxylase is the enzyme responsible for converting progesterone  into aldosterone and cortisol.
• Progesterone is also used to create testosterone, but this conversion does not rely on the 21-hydroxylase enzyme. In CAH, there is a defect in the 21-hydroxylase enzyme.
• Therefore, because there is extra progesterone floating about that cannot be converted to aldosterone or cortisol, it gets converted to testosterone instead. The result is a patient with low aldosterone, low cortisol and abnormally high testosterone.
• The low cortisol levels stimulates further ACTH production which causes adrenal hyperplasia, this also causes hyperpigmentation of the skin as a byproduct of ACTH production is melanocyte stimulating hormone

PC

*Symptoms depend on genetic sex and age of presentation

• Classic salt losing CAH can present with an adrenal crisis