Steroid Replacement in Addison's Disease and in Subjects Adrenalectomized for Cushing's Disease: Comparison of Various Glucocorticoids*

The efficacies of four different glucocorticoids as replacement therapy in Addison's disease or after adrenalectomy for Cushing's disease were compared by assessment of plasma ACTH and free plasma glucocorticoid levels determined by a radioreceptor assay (RRA). Twelve patients were maintained on 9α-fluorocortisol (0.05–0.1 mg/day) and received cortisone acetate (25 mg at 0800 h; 12.5 mg at 2000 h) on day 1, hydrocortisone hemisuccinate (20 mg at 0800 h; 10 mg at 2000 h) on day 2, dexamethasone (0.5 mg at 0800 h; 0.5 mg at 2000 h) on day 3, 9α-fluorocortisol alone on day 4, and prednisolone (5 mg at 0800 h; 2.5 mg at 2000 h) on day 5 of study. Plasma glucocorticoid levels after cortisone acetate, hydrocortisone, or prednisolone treatment reached peak values 1 h after administration, as measured by RRA; for all three steroids, levels were significantly below normal by 0800 h the next morning. In contrast, glucocorticoid levels, measured by RRA, attained peak levels 2 h after dexamethasone treatment, with a much more sustained action; levels were still normal at 0800 h on the following day. One of the 12 patients had Nelson's syndrome, with ACTH levels approximately 15,000 pg/ml, which suppressed incompletely with all steroids. Four patients on long term replacement therapy had undetectably low levels of ACTH even 36 h after glucocorticoid withdrawal. In the remaining 7 patients, there was a marked difference between dexamethasone and the other steroids in terms of ACTH suppression. For equivalent plasma glucocorticoid RRA activity, dexamethasone appeared 35–50 times as potent as hydrocortisone in terms of suppressing ACTH. We conclude 1) that dexamethasone appears to achieve effective control of ACTH secretion in hypoadrenal patients with normally responsive ACTH at the lowest total glucocorticoid dose, as judged by RRA; and 2) that prolonged glucocorticoid replacement therapy, even with short-acting steroids, may lead to suppressed ACTH secretion which responds sluggishly to steroid withdrawal. Where the therapeutic aim is prolonged ACTH suppression with minimal systemic glucocorticoid side effects, as, for example, in congenital adrenal hyperplasia, dexamethasone may be the preferred treatment.