The HPA axis response to critical illness: New study results with diagnostic and therapeutic implications

For decades, elevated plasma cortisol concentrations in critically ill patients were exclusively ascribed to a stimulated hypothalamus-pituitary-adrenal axis with increased circulating adrenocorticotropic hormone (ACTH) inferred to several-fold increase adrenal cortisol synthesis. However, 'ACTH-cortisol dissociation' has been reported during critical illness, referring to low circulating ACTH coinciding with elevated circulating cortisol. It was recently shown that metabolism of cortisol is significantly reduced in critically ill patients explained by a suppression of the activity and expression of cortisol metabolizing enzymes in kidney and liver. This reduced cortisol breakdown determines hypercortisolemia, much more than increased cortisol production, in the critically ill. Although the low plasma ACTH concentrations, evoked by the elevated plasma cortisol via feedback inhibition, are part of this adaptation, they may negatively affect adrenocortical structure and function in the prolonged phase of critical illness. These new insights have implications for diagnosis and treatment of adrenal insufficiency in critically ill patients. (C) 2014 Elsevier Ireland Ltd. All rights reserved.