Which of the following is the most common cause of congenital adrenal hyperplasia, diagnosed by the 17α-hydroxyprogesterone assay?

• A. 17α-Hydroxylase deficiency; progesterone assay
• B. 21-Hydroxylase deficiency; 17α-hydroxyprogesterone assay
• C. 3β-Hydroxysteroid dehydrogenase deficiency; 17α-hydroxyprogesterone assay
• D. 11β-Hydroxylase deficiency; 11-deoxycortisol assay

Answer: (B)

The main idea is that the most common cause of congenital adrenal hyperplasia is a deficiency in the enzyme that acts early in cortisol synthesis, specifically 21-hydroxylase. When this enzyme is lacking, 17α-hydroxyprogesterone cannot be efficiently converted downstream, so it accumulates in the blood. That buildup is what the 17α-hydroxyprogesterone assay detects, making it the standard screening marker for CAH. Because most classic CAH cases arise from 21-hydroxylase deficiency, this assay is the best initial test to identify the condition.

Other enzyme defects in the pathway produce different steroid abnormalities and not a typical rise in 17α-hydroxyprogesterone. For example, 17α-hydroxylase deficiency alters sex steroid and mineralocorticoid balance in a way that doesn’t rely on elevated 17-OHP as the primary screening marker. 3β-HSD deficiency changes the pattern of several upstream steroids, and 11β-hydroxylase deficiency leads to excess 11-deoxycortisol rather than a characteristic 17-OHP elevation.