Clinical aspects of glucocorticoid sensitivity.
Recent studies demonstrate that primary (hereditary) abnormalities in the glucocorticoid receptor gene make 6.6% of the normal population relatively "hypersensitive" to glucocorticoids, while 2.3% are relatively "resistant." These abnormalities might explain why some individuals develop severe adverse effects during low dose glucocorticoid therapy, while others do not develop side effects even during long-term therapy with a much higher dose. Awareness of this heterogeneity in glucocorticoid sensitivity in the normal population might eventually allow the prediction of a "safe" dose of glucocorticoid in individual patients. "Resistance" to the beneficial clinical effects of glucocorticoid therapy in part of the patients with severe rheumatoid arthritis and asthma is probably rarely related to generalized primary (hereditary) glucocorticoid resistance. In the majority of patients this "resistance" seems to be acquired and localized to the sites of inflammation, where it reflects high local cytokine production, which interferes with glucocorticoid action. Recognition of localized, acquired glucocorticoid resistance is of great importance indicating as alternative drug therapy with other immune-modulating drugs like cyclosporin and methotrexate. Chronic high dose glucocorticoid treatment in such patients is ineffective in alleviating symptomatology, while generalized side effects occur, reflecting the patient's normal systemic sensitivity to these drugs.
Lamberts
S W
SW
Department of Medicine, Erasmus University, Rotterdam, The Netherlands.
Huizenga
A T
AT
de Lange
P
P
de Jong
F H
FH
Koper
J W
JW
D000368:Aged; D004305:Dose-Response Relationship, Drug; D004351:Drug Resistance / Q000235:genetics; D005938:Glucocorticoids / Q000009:adverse effects / Q000627:therapeutic use*; D006801:Humans; D007154:Immune System Diseases / Q000150:complications* / Q000188:drug therapy / Q000453:epidemiology; D011965:Receptors, Glucocorticoid / Q000235:genetics*
D005938:Glucocorticoids; D011965:Receptors, Glucocorticoid