Mechanisms and clinical consequences of critical illness associated adrenal insufficiency

Adrenal insufficiency is being diagnosed with increasing frequency in critically ill patients. There exists, however, much controversy in the literature as to the nature of this entity, including its pathophysiology, epidemiology, diagnosis and treatment. The review summarizes our current understanding of the causes and consequences of adrenal insufficiency in critically ill patients.

Activation of the hypothalamic-pituitary-adrenal axis with the production of cortisol is a fundamental component of the stress response and is essential for survival of the host. Dysfunction of the hypothalamic-pituitary-adrenal axis with decreased glucocorticoid activity is being increasingly recognized in critically ill patients, particularly those with sepsis. This condition is best referred to as 'critical illness-related corticosteroid insufficiency'. Critical illness-related corticosteroid insufficiency may occur due to dysfunction at any point in the hypothalamic-pituitary-adrenal axis including tissue glucocorticoid resistance. Critical illness-related corticosteroid insufficiency leads to an exaggerated proinflammatory response with increased tissue injury and organ dysfunction.

Critical illness-related corticosteroid insufficiency is common in critically ill patients, particularly those with sepsis. Supplemental corticosteroids may restore the balance between the pro-and anti-inflammatory mediators in patients with severe sepsis, septic shock and acute respiratory distress syndrome, and thereby improve the outcome of patients with these conditions.