Assessment of the hypothalamic-pituitary-adrenal axis in critical illness

Cortisol is the main corticosteroid secreted from the human adrenal cortex, and it has a crucial role for survival in stressful conditions. An adequate increase in levels of cortisol helps patients to cope with the severity of the disease in the acute phase of critical illness. Either higher or lower than expected cortisol levels were found to be related to increased mortality. Prolonged activation of the hypothalamic-pituitary-adrenal (HPA) axis can result in hypercortisolemia or hypocortisolemia; both can be detrimental to recovery from critical illness. Primary and secondary adrenal insufficiency, relative adrenal insufficiency, tissue resistance to glucocorticoids, adrenocorticotrophic hormone deficiency and immune-mediated inhibition of the HPA axis can be the cause of the impairment of the secretion or action of cortisol in critically ill patients. Recently, some authors offered the term 'critical illness-related corticosteroid insufficiency' to better point out the relative adrenal insufficiency that is seen during critical illness. Patients with critical illness-related corticosteroid insufficiency not only have insufficient circulating cortisol but also have impaired cellular utilization of cortisol. In this article, how adrenal dysfunction presents in critical illness and how appropriate diagnosis and management can be achieved in the critical care setting will be discussed.