Investigation of the mechanism of hypertension in apparent mineralocorticoid excess.
Apparent mineralocorticoid excess (AME) is a rare form of low renin hypertension caused by deficiency of 11 beta-hydroxysteroid dehydrogenase (11 beta-HSD), the enzyme responsible for conversion of cortisol to the bio-inactive metabolite, cortisone. This results in prolonged cortisol half-life, activation of type I (mineralocorticoid) receptors by cortisol, sodium and fluid retention, and consequent childhood-onset hypertension. The cortisol secretion rate is low, perhaps due to cortisol's binding to type II (glucocorticoid) receptors and suppressing corticotropin secretion. Patients with AME thus lack stigmata of Cushing's syndrome. To evaluate any potential contribution of the type II (glucocorticoid) receptor to the development of hypertension in AME patients, we administered RU486, a steroid analogue that acts as a pure type II receptor blocker. Selective glucocorticoid receptor blockade did not decrease blood pressure in our patient; instead, a significant increase in average blood pressure was observed (125.1 +/- 1.7 pre-RU486 v 144.7 +/- 1.2 during RU486 treatment, P = .0001). We conclude that the type II receptor does not contribute to the development of hypertension in patients with AME.
Department of Pediatrics, New York Hospital-Cornell University Medical Center, New York.
P W
PW
Speiser
L M
LM
Riddick
K
K
Martin
M I
MI
New
D042842:11-beta-Hydroxysteroid Dehydrogenases; D000293:Adolescent; D005260:Female; D006801:Humans; D006854:Hydrocortisone / Q000097:blood; D006913:Hydroxysteroid Dehydrogenases / Q000172:deficiency*; D006973:Hypertension / Q000209:etiology*; D015735:Mifepristone / Q000627:therapeutic use; D008901:Mineralocorticoids / Q000378:metabolism*; D011965:Receptors, Glucocorticoid / Q000502:physiology; D018161:Receptors, Mineralocorticoid; D011987:Receptors, Steroid / Q000502:physiology
D008901:Mineralocorticoids; D011965:Receptors, Glucocorticoid; D018161:Receptors, Mineralocorticoid; D011987:Receptors, Steroid; D015735:Mifepristone; D006913:Hydroxysteroid Dehydrogenases; D042842:11-beta-Hydroxysteroid Dehydrogenases; D006854:Hydrocortisone