help button home button Endocrine Society JCEM
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
This Article
Right arrow Submit a related Letter to the Editor
Right arrow Alert me when this article is cited
Right arrow Alert me when eLetters are posted
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow Request Copyright Permission
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Laue, L.
Right arrow Articles by Chrousos, G. P.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Laue, L.
Right arrow Articles by Chrousos, G. P.

Journal of Clinical Endocrinology & Metabolism, Vol 67, 602-606, Copyright © 1988 by Endocrine Society

ARTICLES

The antiglucocorticoid and antiprogestin steroid RU 486: its glucocorticoid agonist effect is inadequate to prevent adrenal insufficiency in primates

L Laue, W Gallucci, DL Loriaux, R Udelsman and GP Chrousos
Developmental Endocrinology Branch, National Institute of Child Health and Human Development, Bethesda, Maryland 20892.

The glucocorticoid receptor antagonist RU 486 has been used to treat the hypercortisolism of patients with nonpituitary Cushing's syndrome. Since endogenous cortisol production fluctuates in many patients with either the ectopic ACTH syndrome or adrenocortical tumors, treatment of these patients with a fixed dose of RU 486 introduces the risk of adrenal insufficiency. While RU 486 possesses some glucocorticoid agonist activity in addition to its potent antagonist effects, it is not known whether this intrinsic agonist activity is of sufficient magnitude to prevent adrenal insufficiency and sustain life. To answer this question three groups of bilaterally adrenalectomized cynomolgus monkeys (n = 5/group) were randomized to receive a daily injection of RU 486 (5 mg/kg.day), cortisol (1.25 mg/kg.day), or saline (placebo). All adrenalectomized monkeys received weekly im injections of deoxycorticosterone pivalate (1 mg) to prevent mineralocorticoid deficiency. Five sham-adrenalectomized monkeys served as controls and received im injections of saline (placebo). Blood was collected before adrenalectomy or sham operation and every 3 days postoperatively for measurement of serum electrolytes, blood urea nitrogen, and creatinine; plasma ACTH concentrations; and complete blood and differential cell counts. All sham-operated and cortisol-replaced adrenalectomized monkeys survived, and none developed overt biochemical evidence of adrenal insufficiency. All placebo and RU 486-replaced adrenalectomized monkeys expired within 33 days after adrenalectomy, presumably from adrenal insufficiency. These findings suggest that while RU 486 is a partial glucocorticoid agonist, its degree of glucocorticoid agonism is inadequate to prevent adrenal insufficiency and support life in adrenalectomized primates.


This article has been cited by other articles:


Home page
 Eur J EndocrinolHome page
S. Johanssen and B. Allolio
Mifepristone (RU 486) in Cushing's syndrome
Eur. J. Endocrinol., November 1, 2007; 157(5): 561 - 569.
[Abstract] [Full Text] [PDF]


HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Endocrinology Endocrine Reviews J. Clin. End. & Metab.
Molecular Endocrinology Recent Prog. Horm. Res. All Endocrine Journals
Copyright © 1988 by The Endocrine Society