A neonate with ambiguous genitalia, 46,XX karyotype, and elevated 17-hydroxyprogesterone is diagnosed with congenital adrenal hyperplasia due to 21-hydroxylase deficiency. The enzymatic block causes accumulation of substrate that is shunted to:

• A Aldosterone via alternative mineralocorticoid pathway
• B Androgens (DHEA and androstenedione) via intact 17,20-lyase pathway ✓
• C Cortisol via 11β-hydroxylase bypass
• D Estrogens via aromatase activity in the adrenal

Explanation

21-hydroxylase (CYP21A2) is required to convert 17-hydroxyprogesterone → 11-deoxycortisol (cortisol pathway) and progesterone → 11-deoxycorticosterone (mineralocorticoid pathway). When blocked, 17-OHP and precursors accumulate and are redirected through the intact 17,20-lyase (CYP17A1) step toward DHEA and androstenedione (androgens). These are peripherally converted to testosterone, causing virilization of 46,XX females (ambiguous genitalia) and precocious puberty. Aldosterone synthesis is impaired (salt-wasting form). Cortisol cannot be made via a bypass — its deficiency drives ACTH hypersecretion worsening substrate accumulation.

Reference: Robbins & Cotran Pathologic Basis of Disease, 10th ed.

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Written and medically reviewed by the StethoPrep medical team.