Adrenal Insufficiency in Critically Ill Patients: Conceptual Evolution, Pathophysiology, Diagnosis, and Therapeutic Recommendations
Rafael Reaño Ortega
ABSTRACT
Corticosteroid insufficiency associated with critical illness (CIRCI) represents a dysfunction in the hypothalamic-pituitary-adrenal (HPA) axis that adapts to stress in patients suffering from severe conditions. This condition is different from a complete lack of cortisol and is marked by changes in cortisol metabolism, such as decreased levels of carrier globulin, central inhibition of the HPA axis, and peripheral resistance through glucocorticoid receptors. This review encapsulates experimental, translational, and clinical research concerning HPA axis regulation, cortisol availability, receptor signaling, and both diagnostic and therapeutic aspects of CIRCI. It highlights the adaptive nature of endocrine responses while also noting the possible inadequacies of total cortisol as a biomarker. In cases of severe illness, free cortisol levels may rise despite low ACTH due to reduced clearance rates and transporter protein functionality. Research indicates a weak correlation between standard testing methods and clinical outcomes. Hydrocortisone has been shown to alleviate shock and decrease reliance on vasopressors in septic shock scenarios, although its effects on mortality are varied. Lastly, assessing CIRCI necessitates consideration of a wider array of clinical and functional indicators beyond merely biochemical thresholds.
