Congenital Adrenal Hyperplasia - Overview

Steroid pathway

All CAH are due to autosomal recessive mutations.

21-hydroxylase deficiency accounts for 90-95% of cases.

  • Classical is severe 21-hydroxylase deficiency with salt-wasting (hyponatraemia, hypokalaemia, alkalosis, hypotension), ambiguous genitalia in genetically female infants.
  • Simple virilizing is more mild 21-OH deficiency causing virilization in childhood, including accelerated linear growth and skeletal maturation, early pubic hair and early phallic enlargement or clitoromegaly.
  • Non-classical is mildest 21-OH deficiency, causing hyperandrogenism/infertility in adult females, and unlikely to be detected in adult males.

11β-hydroxylase deficiency accounts for 5-8% of cases.

  • Early-onset hypertension, mild to moderate - presumed due to excess DOC, though does not correlate well with DOC levels.
  • Rarely, infants may also present with salt-wasting - this seems to be due to mineralocorticoid resistance in infancy, DOC failing to substitute for aldosterone.
  • Moderate virilzation occurs, typically with some virilization of external genitalia in females, and early puberty.

17α-hydroxylase deficiency

  • Mineralocorticoid excess - hypertension, hypokalaemic alkalosis
  • Sex steroid deficiency (normal female infants but no puberty; male infants range from female to underdeveloped male, again no puberty)
  • Cortisol deficiency (but 50-100 times normal levels of corticosterone prevent adrenal crisis).

3β-HSD2 deficiency

  • Mineralocorticoid deficiency
  • Glucocorticoid deficiency
  • Excess DHEA (a weak androgen which can cause mild virilization in females, but may be inadequate for normal male development, i.e. ambiguous genitalia possible in both sexes).