Endocrine Responses to Critical Illness: Novel Insights and Therapeutic Implications

Context: Critical illness, an extreme form of severe physical stress, is characterized by important endocrine and metabolic changes. Due to critical care medicine, survival from previously lethal conditions has become possible, but many patients now enter a chronic phase of critical illness. The role of the endocrine and metabolic responses to acute and prolonged critical illness in mediating or hampering recovery remains highly debated. Evidence Acquisition: The recent literature on changes within the hypothalamic-pituitary-thyroid axis and the hypothalamic-pituitary-adrenal axis and on hyperglycemia in relation to recovery from critical illness was critically appraised and interpreted against previous insights. Possible therapeutic implications of the novel insights were analyzed. Specific remaining questions were formulated. Evidence Synthesis: In recent years, important novel insights in the pathophysiology and the consequences of some of these endocrine responses to acute and chronic critical illness were generated. Acute endocrine adaptations are directed toward providing energy and substrates for the vital fight-or-flight response in a context of exogenous substrate deprivation. Distinct endocrine and metabolic alterations characterize the chronic phase of critical illness, which seems to be no longer solely beneficial and could hamper recovery and rehabilitation. Conclusions: Important novel insights reshape the current view on endocrine and metabolic responses to critical illness and further clarify underlying pathways. Although many issues remain unresolved, some therapeutic implications were already identified. More work is required to find better treatments, and the optimal timing for such treatments, to further prevent protracted critical illness, to enhance recovery thereof, and to optimize rehabilitation.