OBJECTIVE: The definition of normal adrenal function in critically ill patients remains controversial, despite a large body of literature. We review the clinical presentation, diagnosis, and treatment of adrenal insufficiency in critically ill patients and discuss the authors' personal approach to patient management. METHODS: Extensive literature review, guidelines from professional societies, and personal experience. RESULTS: A decrease in cortisol breakdown rather than an increase in cortisol production has been suggested as the main contributor to elevated cortisol levels in critically ill patients. The concept of relative adrenal insufficiency has multiple pathophysiologic flaws and is not supported by current evidence. Patients with septic shock who are pressor dependent or refractory to fluid resuscitation may receive a short course of hydrocortisone regardless of their serum cortisol levels or their response to a cosyntropin stimulation test (CST). Patients without septic shock who are suspected to have adrenal insufficiency should have their random cortisol levels measured. In patients with low and near-normal cortisol-binding proteins, a serum cortisol of <10 or 15 μg/dL, respectively, may trigger need for glucocorticoid treatment. Assays of free cortisol levels offer an advantage over total cortisol levels in patients with low binding proteins. Most critically ill patients have a normal random free cortisol level of >1.8 μg/dL, although further studies are needed to define a normal range in critically ill patients based on both severity and duration of illness. A CST may be used to further evaluate adrenal function in patients without septic shock who have borderline random serum or free cortisol levels. CONCLUSION: Evaluation of adrenal function in critically ill patients is complex. Recent findings of decreased cortisol breakdown in critically ill patients as the main contributor to elevated cortisol levels calls for better-designed studies to explore the optimal evaluation and treatment of adrenal insufficiency in critically ill patients. ABBREVIATIONS: ACTH = adrenocorticotropic hormone; AI = adrenal insufficiency; CBG = corticosteroid-binding globulin; CORTICUS = Corticosteroid Therapy of Septic Shock; CRH = corticotropin-releasing hormone; CST = cosyntropin stimulation test; GC = glucocorticoid; GR = glucocorticoid receptor; HPA = hypothalamic-pituitary-adrenal; IL = interleukin; RAI = relative adrenal insufficiency.
OBJECTIVE: The definition of normal adrenal function in critically illpatients remains controversial, despite a large body of literature. We review the clinical presentation, diagnosis, and treatment of adrenal insufficiency in critically illpatients and discuss the authors' personal approach to patient management. METHODS: Extensive literature review, guidelines from professional societies, and personal experience. RESULTS: A decrease in cortisol breakdown rather than an increase in cortisol production has been suggested as the main contributor to elevated cortisol levels in critically illpatients. The concept of relative adrenal insufficiency has multiple pathophysiologic flaws and is not supported by current evidence. Patients with septic shock who are pressor dependent or refractory to fluid resuscitation may receive a short course of hydrocortisone regardless of their serum cortisol levels or their response to a cosyntropin stimulation test (CST). Patients without septic shock who are suspected to have adrenal insufficiency should have their random cortisol levels measured. In patients with low and near-normal cortisol-binding proteins, a serum cortisol of <10 or 15 μg/dL, respectively, may trigger need for glucocorticoid treatment. Assays of free cortisol levels offer an advantage over total cortisol levels in patients with low binding proteins. Most critically illpatients have a normal random free cortisol level of >1.8 μg/dL, although further studies are needed to define a normal range in critically illpatients based on both severity and duration of illness. A CST may be used to further evaluate adrenal function in patients without septic shock who have borderline random serum or free cortisol levels. CONCLUSION: Evaluation of adrenal function in critically illpatients is complex. Recent findings of decreased cortisol breakdown in critically illpatients as the main contributor to elevated cortisol levels calls for better-designed studies to explore the optimal evaluation and treatment of adrenal insufficiency in critically illpatients. ABBREVIATIONS: ACTH = adrenocorticotropic hormone; AI = adrenal insufficiency; CBG = corticosteroid-binding globulin; CORTICUS = Corticosteroid Therapy of Septic Shock; CRH = corticotropin-releasing hormone; CST = cosyntropin stimulation test; GC = glucocorticoid; GR = glucocorticoid receptor; HPA = hypothalamic-pituitary-adrenal; IL = interleukin; RAI = relative adrenal insufficiency.
Authors: Laura E Dichtel; Melanie Schorr; Claudia Loures de Assis; Elizabeth M Rao; Jessica K Sims; Kathleen E Corey; Puja Kohli; Patrick M Sluss; Michael J McPhaul; Karen K Miller Journal: J Clin Endocrinol Metab Date: 2019-10-01 Impact factor: 5.958