Combined 17?-hydroxylase/17,20-lyase deficiency is a disorder of steroidogenesis associated with a broad range of clinical presentations. The steroid abnormalities result in a rare form of congenital adrenal hyperplasia (CAH) that accounts for about 1% of cases of CAH overall. The 17?-hydroxylase deficiency leads to diminished cortisol production, although adrenal insufficiency is rare because hypersecretion of ACTH leads to increased corticosterone production. However, overproduction of mineralcorticoids also occurs due to hypersecretion of ACTH, and this often results in hypokalemia and early-onset hypertension in 85-90% of cases. The steroid abnormalities also affect production of enzymes needed to make hormones involved in sexual development. 46,XY individuals typically have female external genitalia, a blind vaginal pouch, and absence of Mullerian structures, although ambiguous genitalia and hypospadias with cryptorchidism have been reported. 46,XX individuals have normal female external genitalia but typically present at puberty due to lack of development of secondary sexual characteristics (“sexual infantilism”) and absent or irregular menses.
In rare cases, individuals with isolated 17,20-lyase deficiency have been reported. These individuals do not exhibit symptoms of mineralcorticoid excess as 17?-hydroxylase activity is retained. 46,XY individuals with isolated 17,20-lyase deficiency typically present in infancy with ambiguous genitalia or inguinal hernias.