First, unlike what is generally assumed, not the presence of septic shock, but rather an extended duration of ICU stay beyond 4 weeks explains lack of elevated free cortisol that is not compensated by increased ACTH, which could be due to a central (endogenous or exogenous) adrenocortical suppression. Second, cosyntropin stimulation tests, currently advised for the diagnosis of critical illness-related corticosteroid insufficiency (CIRCI), are confounded by increased cortisol distribution volume—which lowers the incremental total but not free cortisol responses to cosyntropin—and thus these tests cannot provide reliable information on the adrenocortical integrity or functional reserve.