Which enzyme deficiency underlies most cases of congenital adrenal hyperplasia and what hormone pathway is affected?

• A. 11-beta-hydroxylase; increased mineralocorticoids.
• B. 17-alpha-hydroxylase; decreased androgens.
• C. 21-hydroxylase; impaired cortisol and aldosterone synthesis with excess androgen production.
• D. 3-beta-HSD; decreased sex steroids.

Answer: (C)

This question centers on how a specific adrenal enzyme defect reshapes steroid production. The most common cause of congenital adrenal hyperplasia is a deficiency in 21-hydroxylase. This enzyme is needed to complete the pathways making cortisol and the mineralocorticoid aldosterone. When 21-hydroxylase is deficient, cortisol and aldosterone synthesis are impaired, leading to low cortisol levels and low aldosterone. The drop in cortisol removes the negative feedback on the pituitary, so ACTH rises and stimulates the adrenal cortex to grow (hyperplasia). The precursor molecules that would normally go toward cortisol and aldosterone production get redirected into the androgen pathway, resulting in excess androgens.

That’s why this option best fits: it describes impaired cortisol and aldosterone synthesis with excess androgen production, the classic pattern of the most common CAH. Other enzyme defects produce different patterns—11-beta-hydroxylase deficiency increases androgen and mineralocorticoid precursors with hypertension; 17-alpha-hydroxylase deficiency lowers sex steroids and can raise mineralocorticoids; 3-beta-HSD deficiency reduces multiple steroids, leading to broad deficits—so they don’t match the classic CAH presentation as closely.