Cortisol metabolism in critical illness: implications for clinical care.
OBJECTIVE
Critical illness is uniformly characterized by elevated plasma cortisol concentrations, traditionally attributed exclusively to increased cortisol production driven by an activated hypothalamic pituitary adrenal axis. However, as plasma adrenocorticotropic hormone (ACTH) concentrations are often not elevated or even low during critical illness, alternative mechanisms must contribute.


RESULTS
Recent investigations revealed that plasma clearance of cortisol is markedly reduced during critical illness, explained by suppressed expression and activity of the main cortisol metabolizing enzymes in liver and kidney. Furthermore, unlike previously inferred, cortisol production rate in critically ill patients was only moderately increased to less than double that of matched healthy subjects. In the face of low-plasma ACTH concentrations, these data suggest that other factors drive hypercortisolism during critical illness, which may suppress ACTH by feedback inhibition. These new insights add to the limitations of the current diagnostic tools to identify patients at risk of failing adrenal function during critical illness. They also urge to investigate the impact of lower hydrocortisone doses than those hitherto used.


CONCLUSIONS
Recent novel insights reshape the current understanding of the hormonal stress response to critical illness and further underline the need for more studies to unravel the pathophysiology of adrenal (dys)functioning during critical illness.
Clinical Division and Laboratory of Intensive Care Medicine, Department of Cellular and Molecular Medicine, KU Leuven, Leuven, Belgium.
Eva
E
Boonen
Greet
G
Van den Berghe
D000309:Adrenal Insufficiency / Q000276:immunology / Q000401:mortality / Q000503:physiopathology*; D016638:Critical Illness; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D006854:Hydrocortisone / Q000008:administration & dosage* / Q000276:immunology / Q000378:metabolism*; D007362:Intensive Care Units; D008297:Male; D010912:Pituitary-Adrenal Function Tests; D010913:Pituitary-Adrenal System / Q000276:immunology / Q000503:physiopathology*; D016896:Treatment Outcome
D006854:Hydrocortisone