Hypothalamic Pituitary Adrenal Function during Critical Illness: Limitations of Current Assessment Methods

• Published in: The journal of clinical endocrinology and metabolism 2006-10, Vol.91 (10), p.3725-3745
• Main Author: Arafah, Baha M.
• Format: Article
• Language: English
• Subjects: Adrenal Glands - physiology; Adrenal Insufficiency - etiology; Critical Illness; Dehydroepiandrosterone - blood; Dehydroepiandrosterone Sulfate - blood; Endotoxemia - physiopathology; Glucocorticoids - therapeutic use; Hemodilution; Humans; Hydrocortisone - blood; Hypothalamo-Hypophyseal System - physiopathology; Pituitary-Adrenal System - physiopathology; Plasma Volume; Stress, Psychological - physiopathology
• ISSN: 0021-972X; 1945-7197
• DOI: 10.1210/jc.2006-0674

Context: Activation of the hypothalamic-pituitary-adrenal (HPA) axis represents one of several important responses to stressful events and critical illnesses. Despite a large volume of published data, several controversies continue to be debated, such as the definition of normal adrenal response, the concept of relative adrenal insufficiency, and the use of glucocorticoids in the setting of critical illness. Objectives: The primary objective was to review some of the modulating factors and limitations of currently used methods of assessing HPA function during critical illness and provide alternative approaches in that setting. Design: This was a critical review of relevant data from the literature with inclusion of previously published as well as unpublished observations by the author. Data on HPA function during three different forms of critical illnesses were reviewed: experimental endotoxemia in healthy volunteers, the response to major surgical procedures in patients with normal HPA, and the spontaneous acute to subacute critical illnesses observed in patients treated in intensive care units. Setting: The study was conducted at an academic medical center. Patients/Participants: Participants were critically ill subjects. Intervention: There was no intervention. Main Outcome Measure: The main measure was to provide data on the superiority of measuring serum free cortisol during critical illness as contrasted to those of total cortisol measurements. Results: Serum free cortisol measurement is the most reliable method to assess adrenal function in critically ill, hypoproteinemic patients. A random serum free cortisol is expected to be 1.8 μg/dl or more in most critically ill patients, irrespective of their serum binding proteins. Because the free cortisol assay is not currently available for routine clinical use, alternative approaches to estimate serum free cortisol can be used. These include calculated free cortisol (Coolens’ method) and determining the free cortisol index (ratio of serum cortisol to transcortin concentrations). Preliminary data suggest that salivary cortisol measurements might be another alternative approach to estimating the free cortisol in the circulation. When serum binding proteins (albumin, transcortin) are near normal, measurements of total serum cortisol continue to provide reliable assessment of adrenal function in critically ill patients, in whom a random serum total cortisol would be expected to be 15 μg/dl or more in most pa