Arafah BM - As anecdotal reports without supporting pharmacokinetic data are the basis for perioperative glucocorticoid therapy for patients with adrenal insufficiency (AI). In 22 dexamethasone-suppressed healthy individuals, the half-life (t1/2), clearance and volume of distribution of two consecutive IV-administered hydrocortisone (HC; 15 or 25 mg every 6 hours) were determined and the acquired data were used to develop a novel protocol to manage 68 patients with AI requiring surgical procedures. In healthy individuals, longer cortisol t1/2 was noted when they were administered a higher HC dose and it was longer in patients than in healthy individuals given the same HC dose. Findings suggest that in the postoperative period, patients with AI undergoing major surgery exhibit altered cortisol pharmacokinetics and could be administered lower doses of HC safely. Findings thereby argue the current practice of offering excessive glucocorticoid supplementation during stress.