Adrenal Steroids and Hypertension

Abstract

It is estimated that 20% of all hypertensive patients have unexplained suppression of plasma renin that is not related to age. These patients with hypertension respond dramatically to diuretic therapy, but are vulnerable to the hypokalemic effects and magnesium depleting effects of diuretics. They express “mineralocorticoid hypertension” (MCH) characteristics which are derived from clinical studies of primary hyperaldosteronism and experimental models of hypertension utilizing deoxycorticosterone (DOC) and aldosterone in laboratory animals. Major advances have been made in understanding the role of both mineralocorticoids (MC) and glucocorticoids in the development of hypertension. With the description of the disorder “apparent miner alocorticoid excess” (AME), it is now clear that glucocorticoids such as cortisol can occupy the MC receptor. It is of considerable interest that the syndrome of AME can be reproduced by blocking the action of 11-hydroxysteroid dehydrogenase with derivatives of licorice and carbenaxolone, allowing access of cortisol to the MC receptor. Other advances include the clarification of the biochemical genetics of “glucocorticoid suppressible aldosteronism” where 18-oxo-cortisol and 18-hydroxycortisol, two hybrid steroids, are produced because of a fusion of the gene encoding 1 β-hydroxylase and aldosterone synthase. Another advance includes the demonstration that both DOC and 19-nor-deoxycorticosterone (19-nor-DOC) are formed in excess in Cushing's syndrome and in 11-hydroxylase and 17-hydroxylase deficiencies. Finally, it is likely that future MCH syndromes will be described, since a large proportion of the hypertensive population exhibits easily provokable hypokalemia and suppressed plasma renin activity.