Journal of Clinical Endocrinology & Metabolism, Vol 74, 963-967, Copyright © 1992 by Endocrine Society

ARTICLES

Cortisol inactivation overload: a mechanism of mineralocorticoid hypertension in the ectopic adrenocorticotropin syndrome

S Ulick, JZ Wang, JD Blumenfeld and TG Pickering
Veterans Affairs Hospital, Bronx, New York 10468.

The more severe mineralocorticoid manifestations in the ectopic ACTH syndrome compared to pituitary Cushing's disease have been attributed to hypersecretion of 11-deoxycorticosterone. Another difference between the two forms of ACTH-excess, however, is a more severe degree of hypercortisolism in the ectopic syndrome. Cortisol can become a potent mineralocorticoid if its peripheral metabolism is interfered with as occurs in the syndrome of apparent mineralocorticoid excess. This mechanism also occurs in an experimental model of the apparent mineralocorticoid excess syndrome induced by licorice derivatives. We have tested the hypothesis that cortisol is a major mineralocorticoid in the ectopic ACTH syndrome because of two factors, marked hypersecretion and incomplete peripheral metabolism of cortisol as a result of an overload of metabolizing enzymes. Two measures of the peripheral metabolism of cortisol were found to be markedly decreased in two patients with the ectopic ACTH syndrome. The cortisol turnover quotients were 17.2 and 19.6 (normal = 215 +/- 98) and the ring A reduction constants were 11.8 and 13.8 (normal = 101 +/- 23). These values were comparable to that found in the syndrome of apparent mineralocorticoid excess and consistent with the hypothesis that cortisol is a significant functioning mineralocorticoid in the ectopic ACTH syndrome.

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