Modern approach to corticosteroid replacement therapy

Abstract

The therapeutic index of corticosteroids for adrenal insufficiency is narrowing with recognition of the adverse consequences from even minor overtreatment. As in endogenous Cushing syndrome, chronically excessive glucocorticoid dosage can produce weight gain, hypertension, hypercholesterolemia, glucose intolerance, and bone demineralization. By contrast, deficient replacement leads to the constitutional and other symptoms of adrenal insufficiency and can induce lifethreatening shock, particularly during major stress. Optimum therapy depends on the cause of adrenal insufficiency. Primary and secondary adrenal insufficiency, congenital adrenal hyperplasia, and Nelson syndrome each present unique problems that require specific approaches to treatment. The clinician's major challenge is to adjust mineralocorticoid and glucocorticoid doses so as to meet physiologic requirements without inducing corticosteroid excess. Herein, we review the patho-physiology of adrenal insufficiency, outline a stepwise approach to adrenal hormone replacement, and discuss literature relevant to current issues of corticosteroid replacement therapy.