Cause and consequence of the altered cortisol metabolism and the role of bile acids during critical illness.

Adrenal release of the stress hormone cortisol is an essential component of the human adaptation to stress, as it prevents shock, fosters the acute provision of energy and protects against excessive inflammation. During the severe stress situation of critical illness, an insufficient adrenal response is common and may be detrimental for the patient. In healthy people, production and release of cortisol from the adrenals is stimulated by the adrenocorticotropic hormone (ACTH). However, the constellation of high cortisol and low ACTH levels during critical illness suggests an ACTH-independent cortisol regulation. We hypothesize that cortisol levels are maintained by a reduced cortisol metabolism in peripheral tissues. The trigger for altering the metabolizing enzymes may be the bile acids, which are increased during critical illness, and which have recently been discovered to be important metabolic and hormonal regulators. Sustained high cortisol levels exert a continuous negative feedback signal on ACTH, resulting in understimulation of the adrenals which may lead to adrenal insufficiency, when additional stress occurs during the course of critical illness. We expect that the results of this study will provide important novel insights in the altered cortisol metabolism during critical illness and, as such, contribute to new diagnostic and therapeutic recommendations.

Keywords:ACTH, Bile Acids, Cortisol, Metabolism, Hypothalamic-pituitary-adrenal axis, Critical illness

Disciplines:Laboratory medicine, Palliative care and end-of-life care, Regenerative medicine, Other basic sciences, Other health sciences, Nursing, Other paramedical sciences, Other translational sciences, Other medical and health sciences