Congenital Adrenal Hyperplasia

Inherited group of disorders characterised by a deficiency in one of the enzymes necessary for cortisol synthesis

Aetiology

  • 90% due to an autosomal recessive 21⍺-hydroxylase deficiency

Pathophysiology

  • 21⍺-hydroxylase deficiency prevents the production of aldosterone and cortisol
  • Increased volume of precursors will be diverted into the androgen pathway → increased testosterone and dihydrotesterone
  • Reduced cortisol stimulates ACTH release and cortical hyperplasia
  • Other enzyme deficiencies will result in varied clinical features depending on the pathway affected (e.g. adrenal insufficiency with no signs of reduced aldosterone or vice versa)

Clinical presentation

Classic CAH

  • Presents at birth or shortly after
  • Genital ambiguity (virilisation) in females
  • Adrenal failure - collapse, hypotension, hypoglycaemia, poor weight gain
    • Biochemical patten of Addison's disease

Non-classic CAH

  • Partial 21⍺-hydroxylase deficiency
  • Presents later (adolescence/adulthood)
    • Precocius puberty
    • Hirsutism
    • Acne
    • Oligomenorrhoea, infertility or sub-fertility

Investigations

  • Basal (or stimulated) 17-OH progesterone
  • Genetic analysis

Management

Paediatrics

  • Glucocorticoid replacement
  • Mineralocorticoid replacement in some
  • Surgical correction
  • Acheive maximal growth

Adults

  • Glucocorticoid replacement, avoiding steroid over-replacement
  • Control androgen excess
  • Restore fertility