Peeters B, et al. - Researchers compared adrenocorticotropic hormone (ACTH) responses to 100 µg IV corticotropin-releasing hormone (CRH) and placebo, given that augmented/prolonged ACTH-responses to CRH injection can be expected with hypothalamic damage, immediately suppressed responses with pituitary damage, and delayed decreased responses in prolonged critical illness with feedback inhibition. In this randomized, double-blind, placebo-controlled crossover cohort study, they assessed three cohorts of 40 matched patients in the acute (ICU-day 3–6), subacute (ICU-day 7–16) or prolonged phase (ICU-day 17–28) of critical illness, along with 20 demographically matched healthy subjects. Findings revealed suppressed ACTH responses to CRH in the more prolonged phases, but not in the acute phase of critical illness. These responses were found to be compatible with feedback inhibition exerted by elevated free cortisol, rather than by cellular damage to hypothalamus and/or pituitary.