Hypersecretion of a new corticosteroid, 18-hydroxycortisol in two types of adrenocortical hypertension.

The most abundant substance in the urinary free steroid fraction of patients with primary aldosteronism has been identified as 18-hydroxycortisol. 18-hydroxycortisol is very likely an adrenocortical secretory product rather than a peripheral metabolite, since it is abundantly synthesized by aldosteronoma tissue slices. The biogenesis of 18-hydroxycortisol takes place from cortisol rather than from 18-hydroxycorticosterone; that is, 17 alpha-precedes 18-hydroxylation. Cortisol 18-hydroxylation appears to be unrelated to the two other types of adrenocortical hydroxylation at this position. The pathway is present to a small extent in the normal human adrenal cortex and is only moderately stimulated by ACTH. Cortisol 18-hydroxylation is markedly accentuated in two circumstances: in the aldosteronoma cell where its presence may serve to distinguish tumor from bilateral hyperplasia and in ACTH-stimulatable hyperaldosteronism where it represents the first qualitative steroid biochemical abnormality to be demonstrated and as such may be useful in diagnosis and genetic studies. The possible contribution of 18-hydroxycortisol to the severity of the clinical manifestations of mineralocorticoid excess in these two types of aldosteronism remains to be explored.