ACTH suppression after oral administration of cortisone in Addisonian and adrenalectomized patients

Plasma cortisol and the corresponding ACTH concentrations were determined before, and for 6 h following a single oral dose of 25 mg cortisone acetate in 7 patients with Addison's disease, 6 patients adrenalectomized for Cushing's disease and 1 patient adrenalectomized for congenital adrenal hyperplasia. The basal plasma cortisol concentrations 12 h after an evening dose of cortisone acetate 12.5 mg were below 100 nmol/l, and the corresponding ACTH concentrations were markedly elevated in all patients. Great interindividual variations were found in cortisol peak concentrations (Cmax) and the time to peak values, but without significant differences between the two patient groups. The maximal ACTH suppression occurred within 60-330 min after the cortisol Cmax, and was not significantly different in the two groups. The suppressed plasma ACTH concentrations were considerably above normal in 3 of the patients with Addison's disease and in 4 of the 6 patients adrenalectomized for Cushing's disease, including 2 patients with Nelson's syndrome. A similar degree of impaired ACTH suppression in patients with Addison's disease as in adrenalectomized patients suggests the occurrence of a secondary hypothalamic-pituitary dysfunction with ACTH hypersecretion in Addison's disease. The adequacy of the commonly used adrenocortical replacement therapy and its possible relation to the impaired ACTH suppression is discussed.