Elevated 17-hydroxyprogesterone is most characteristic of deficiency of which enzyme in congenital adrenal hyperplasia?

• A. 21-hydroxylase
• B. 3β-hydroxysteroid dehydrogenase
• C. 11β-hydroxylase
• D. 17α-hydroxylase

Answer: (A)

Elevated 17-hydroxyprogesterone points to a block at the 21-hydroxylase step in adrenal steroid synthesis. When 21-hydroxylase is deficient, 17-hydroxyprogesterone cannot be efficiently converted to 11-deoxycortisol, so it accumulates in the adrenal glands and in circulation. This buildup is a defining feature of classic congenital adrenal hyperplasia due to 21-hydroxylase deficiency and is the basis for newborn screening. The excess 17-hydroxyprogesterone is then more available to be diverted into androgen production, causing virilization and, in severe cases, salt-wasting from impaired mineralocorticoid synthesis. Other enzyme defects produce different hormonal patterns: for example, 11β-hydroxylase deficiency causes buildup of different steroid precursors and often hypertension; 3β-hydroxysteroid dehydrogenase deficiency alters several steroid pathways with a distinct profile; 17α-hydroxylase deficiency leads to low sex steroids and cortisol with a different steroid pattern.