Adrenal Steroid Synthesis Pathway

Mnemonic

“Salt, sugar, sex: the deeper you go, the sweeter it gets”, for the three cortical zones from outside in:

• Zona Glomerulosa - Glucocorticoid? No: aldosterone, the salt, under angiotensin II and potassium
• Zona Fasciculata - cortisol, the sugar, under ACTH
• Zona Reticularis - androgens, the sex, under ACTH

“GFR” for the zones, “salt, sugar, sex” for the products. The medulla, inside them all, makes catecholamines.

Congenital adrenal hyperplasia is best understood as a block in the pathway:

• 21-hydroxylase deficiency, over 90 per cent of cases: no aldosterone, no cortisol, excess androgens. Salt wasting, hypotension, hyperkalaemia, and virilisation of female infants
• 11-beta-hydroxylase deficiency: excess deoxycorticosterone, so hypertension with hypokalaemia, plus virilisation
• 17-alpha-hydroxylase deficiency: hypertension with no androgens, so undervirilisation

“Blocks below the androgen branch cause virilisation; blocks above it do not.”

Expansion

All adrenal steroids start from cholesterol, converted to pregnenolone by the rate-limiting enzyme cholesterol desmolase under ACTH control. Three parallel branches follow:

• Mineralocorticoid (zona glomerulosa): to aldosterone
• Glucocorticoid (zona fasciculata): to cortisol
• Androgen (zona reticularis): to DHEA and androstenedione

Enzyme blocks in congenital adrenal hyperplasia:

The pattern is deducible rather than memorable: blocking a step diverts substrate into the remaining pathways, so 21-hydroxylase deficiency shunts everything into androgens, causing virilisation of a female infant with salt-losing crisis, while 17-alpha deficiency blocks androgens and causes under-virilisation of a male infant with hypertension.