ADRENOCORTICAL RESPONSE UPON REPEATED STIMULATION WITH CORTICOTROPHIN IN PATIENTS LACKING ENDOGENOUS CORTICOTROPHIN SECRETION

Abstract

ABSTRACT The role played by a normal endogenous corticotrophin secretion in the mechanism by which adrenocortical steroidogenic response to ACTH increases as a result of previous administration of the peptide, was assessed by repeated ACTH administration in 25 patients under prolonged cortico-therapy and in 13 patients with anterior hypophyseal insufficiency. The response to ACTH (250 μg tetracosapeptide iv over 8 h) was evaluated on the basis of changes in plasma cortisol and in the urinary excretion of cortisol and 17-ketogenic steroids. The steroidogenic response to the first ACTH infusion was markedly reduced in these patients when compared to control subjects, or even to subjects on short-term dexametasone. However, in these patients as in normals, acute ACTH administration was followed by a phase, lasting for 3 days at least, during which the steroidogenic response to further ACTH stimulation was increased. When ACTH was infused repeatedly on 4 consecutive days in patients on long-term cortico-therapy, adrenocortical responsiveness was rapidly restored to normal. By contrast, when ACTH was administered every fourth day, a less pronounced enhancement of adrenocortical responsiveness occurred, the secretory activity returning to previous hypo-adrenal state between each stimulation.. These data indicate that the mechanism of amplified adrenocortical response to ACTH does not require continuous endogenous corticotrophin secretion. They further suggest that intermittent corticotrophin therapy may be more adequate in promoting recovery of adrenocortical function on steroid withdrawal than a schedule consisting of daily ACTH administration, since the latter is thought to slow down hypothalamic-pituitary activity because of concomitant sustained enhancement of steroidogenesis.