Pulsatile Administration of Human Corticotropin-Releasing Hormone in Patients with Secondary Adrenal Insufficiency: Restoration of the Normal Cortisol Secretory Pattern

Human corticotropin-releasing hormone (hCRH) was administered in a pulsatile fashion to eight patients with secondary adrenal insufficiency. These patients were selected on the basis of a normal or exaggerated plasma ACTH response to exogenous ovine CRH, suggesting sparing of the corticotrophs. A continuous 48-h iv infusion of ACTH to restore the adrenal glands to an ACTH-responsive state preceded hCRH administration. Eight 1 microgram/kg bolus injections of hCRH were administered in a 24-h period. The time intervals between hCRH injections were selected to resemble the frequency of spontaneously occurring secretory episodes of plasma ACTH and cortisol. Four of the patients underwent a second study, of identical design, in which normal saline injections were administered instead of hCRH. Pulsatile hCRH treatment resulted in a secretory pattern of ACTH and cortisol similar to that in normal subjects. ACTH and cortisol levels during saline administration were low and had no circadian variation. These findings indicate that exogenous CRH is able to restore normal basal ACTH and cortisol secretory patterns when given in an appropriate manner. It is possible that the pulsatile administration of hCRH may prove to be a more physiological technique for restoring adrenal function of patients with corticotroph-sparing secondary adrenal insufficiency and may avoid some of the complications of glucocorticoid administration.