Disorders of steroid 17 alpha-hydroxylase deficiency.

The human P450c17 alpha gene (CYP17) is a single copy gene located in chromosome 10, consisting of 8 exons and 7 introns. 17 alpha-Hydroxylase/17,20-lyase deficiency is one of two hypertensive forms of congenital adrenal hyperplasia and is inherited as an autosomal recessive trait; although rare, it probably exists with twice the frequency of the 11 beta-hydroxylase deficiency. Deficient 17 alpha-hydroxylation of pregnenolone and progesterone and subsequent deficiency of the cleavage of the C-17,20 carbon bond result in the absence of sex hormone formation in both the adrenal glands and the gonads, causing hypogonadism and male pseudohermaphroditism. Elevated and glucocorticoid-suppressible levels of the ZF 17-deoxysteroids--DOC and corticosterone--as well as their 18-hydroxylated products--18-OHDOC and 18-OHB (in addition to 19-nor-DOC)--are responsible for hypertension, hypokalemia, and renin and aldosterone suppression. A few cases, reported primarily among Japanese families, have basal hyperaldosteronism, an enigmatic condition that still demands adequate explanation. Like other forms of congenital adrenal hyperplasia, treatment of 17 alpha-hydroxylase deficiency consists of replacement doses of glucocorticoid hormones and supplemental estrogen therapy in the young adult patient. Heterozygotes may be detected by slightly exaggerated responses of some or all the ZF 17-deoxysteroids to ACTH stimulation, and by the elevated ratio of total urinary metabolites of corticosterone to the total metabolites of cortisol.