Gabriel I Uwaifo, MBBS; Chief Editor: George T Griffing, MD

The rare variant of congenital adrenal hyperplasia (CAH) known as 17-hydroxylase deficiency was first described in the 1960s in patients with sexual infantilism and hypertension. It has also been described to present in the setting of male pseudohermaphroditism. Patients with 17-hydroxylase deficiency have alterations in their CYP17 gene, which encodes the P450C17 enzyme. This enzyme plays a central role in steroidogenesis. Steroidogenesis is essential for the production of cortisol and sex steroids. Thus, patients with 17-hydroxylase deficiency have reduced secretion of cortisol, androgen, and estrogen, with adrenal and gonadal steroidogenesis impairment. Although patients with 17-hydroxylase deficiency have decreased cortisol production, they do not have signs or symptoms of adrenal insufficiency due to elevations of corticosterone and glucocorticoids.

Generic adrenocortical steroidogenesis pathway.

CAH due to 17-hydroxylase deficiency is associated with hypertension and an excess of deoxycorticosterone (DOC), which is the second most common naturally occurring mineralocorticoid after aldosterone. DOC excess typically is associated with hypertension, hypokalemia, and renin and aldosterone suppression. Among the conditions associated with DOC excess are Cushing syndrome (particularly the ectopic adrenocorticotropic hormone [ACTH] variants and in the setting of adrenocortical carcinomas), adrenal tumors, CAH due to 11-hydroxylase deficiency, and primary cortisol resistance.