(A) In normal physiology, the classic pathway of androgen biosynthesis occurs from conversion of 17-hydroxypregnenolone to DHEA and 17-hydroxyprogesterone to androstenedione. (B) In the absence of 21-hydroxylase activity, 17-hydroxyprogesterone accumulates and can be converted to testosterone and dihydrotestosterone through two pathways: the classic pathway and an alternative pathway. Increased expression of cytochrome b5 occurs during adolescence, promoting adrenal androgen production via the classic pathway. 17-OH activity in the alternative pathway is less affected by cytochrome b5 activity. 17-OHPreg=17-hydroxypregnenolone. 17-OHProg=17-hydroxyprogesterone. DHEA=dehydroepiandrosterone. DHT=dihydrotestosterone. P450scc+StAR=P450 side chain cleavage plus steroidogenic acute regulatory protein. 3βHSD=3-beta-hydroxysteroid dehydrogenase. 17-OH=17-hydroxylase/17,20 lyase. b5=cytochrome b5. 21-OH=21-hydroxylase. 11-OH=11-hydroxylase. AS=aldosterone synthase. 17βHSD=17-beta-hydroxysteroid dehydrogenase. 5αR2=5-alpha-reductase type 2. Adapted from J Clin Endocrinol Metab: Congenital adrenal hyperplasia due to steroid 21-hydroxylase deficiency: an Endocrine Society clinical practice guideline 2010, figure 1.1