Prete A, Taylor AE, Bancos I, et al. - In patients with adrenal insufficiency who are exposed to major stress, the researchers sought to identify the most appropriate mode of hydrocortisone delivery. Total serum cortisol and cortisone, free serum cortisol and urinary glucocorticoid metabolite excretion by mass spectrometry were measured. They used linear pharmacokinetic modeling to determine the most appropriate mode and dose of hydrocortisone administration in individuals with adrenal insufficiency exposed to major stress. Serum total cortisol concentrations were highest and most variable in sepsis patients followed by elective surgery with general anesthesia, stress-fighting patients, and acute major trauma patients. Findings suggested that continuous intravenous hydrocortisone infusion in the prevention and treatment of adrenal crisis during major stress should be preferred over intermittent bolus administration.