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.

Urinary excretion of pregnanetriol and 5 -pregnenetriol in two forms of congenital adrenal hyperplasia.

Although congenital adrenal hyperplasia due to 3beta-hydroxysteroid dehydrogenase deficiency generally reveals a predominance of Delta(5)-3beta-hydroxysteroids, on occasion substantial quantities of pregnanetriol have been found as well. It appears that the latter steroid more often occurs in the subjects who have survived beyond infancy. The use of the measurement of pregnanetriol alone may therefore not be relied upon as a sole determinant of the specific form of defective steroidal biogenesis. It is more characteristic of the 21-hydroxylase deficiency. However when both Delta(5)-pregnenetriol and pregnanetriol are measured the ratio of the former to the latter is always considerably below 1.0 in 21-hydroxylase deficiency and always above 1.0 in 3beta-hydroxysteroid dehydrogenase. Furthermore, 11-ketopregnanetriol has been found only in the urine of subjects with the 21-hydroxylase deficiency. Thus, these two forms of defective steroidal biogenesis may be distinguished by the measurement of these three urinary steroidal metabolites.