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1 December 1993 | Volume 119 Issue 11 | Pages 1113-1124
Glucocorticoid resistance results from the partial, albeit apparently generalized, inability of glucocorticoids to exert their effects on target tissues. The condition is associated with compensatory increases in circulating pituitary corticotropin and cortisol, with the former causing excess secretion of both adrenal androgens and adrenal steroid biosynthesis intermediates with salt-retaining activity. The manifestations of glucocorticoid resistance vary from chronic fatigue (perhaps a result of glucocorticoid deficiency in the central nervous system) to various degrees of hypertension with or without hypokalemic alkalosis or hyperandrogenism, or both, caused by increased cortisol and other salt-retaining steroids and adrenal androgens, respectively. In women, hyperandrogenism can result in acne, hirsutism, menstrual irregularities, oligoanovulation, and infertility; in men, it may lead to infertility and in children, to precocious puberty. Different molecular defects, such as point mutations or a microdeletion of the highly conserved glucocorticoid receptor gene, alter the functional characteristics or concentrations of the intracellular receptor and appear to cause glucocorticoid resistance.
The extreme variability in the clinical manifestations of glucocorticoid resistance and its mimicry of many common diseases can be explained by the overall degree of glucocorticoid resistance, differing sensitivity of target tissues to mineralocorticoids or androgens or both, and perhaps different biochemical defects of the glucocorticoid receptor, with selective resistance of certain glucocorticoid responses in specific tissues. The various different symptoms of classic glucocorticoid resistance and the theoretical potential of this condition to appear surreptitiously emphasize the importance of the glucocorticoid receptor in the pathogenesis of human disease.
Author and Article Information
An edited summary of a Clinical Staff Conference held on 30 September 1992 at the Amphitheater, Building 10, Bethesda, Maryland. The conference was sponsored by the National Institute of Child Health and Human Development, National Institutes of Health.
NIH CONFERENCE
Syndromes of Glucocorticoid Resistance
Authors who wish to cite a section of the conference and specifically indicate its author may use this example for the form of reference:
Detera-Wadleigh S. The glucocorticoid receptor gene, p 1119. In: Chrousos GP, moderator. Syndromes of glucocorticoid resistance. Ann Intern Med. 1993; 119:1113-1124.
Requests for Reprints: George P. Chrousos, MD, NIH, Building 10, Room 10N262, Bethesda, MD 20892.
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