Evidence for an aldosterone biosynthetic defect in congenital adrenal hyperplasia

A search was made for an abnormality in aldosterone biosynthesis in congenital adrenal hyperplasia due to a cortisol 21-hydroxylation defect. Examination of the urinary metabolites of potential C-18-oxygenated steroid precursors revealed an abnormal pattern; however, the locus of the defect was not at the C-21 hydroxylation step, but consisted of overproduction of glomerulosa 18-hydroxylation step, but consisted of overproduction of glomerulus 18-hydroxycorticosterone relative to aldosterone, as seen in the type II corticosterone methyl oxidase defect. This abnormality, which was seen in all salt losers and most nonsalt losers, provided evidence for diminished aldosterone secretory reserve even when values of the hormone are normal or elevated. These findings support the concept that salt-losing and nonsalt-losing forms of the cortisol 21-hydroxylation defect differ only in degree and are not different genotypes. An implication of these findings is that all patients with congenital adrenal hyperplasia with an elevated 18-hydroxycorticosterone to aldosterone metabolite ratio should be considered for mineralocorticoid replacement therapy even if their absolute aldosterone values appear to be normal or elevated.