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Total Cortisol Levels Might Not Reflect Adrenal Status in Critically Ill Patients

In patients with low serum albumin levels, total cortisol measures might be artificially low.

Some patients with critical illnesses appear to have inadequate adrenal responses to stress, because their serum total cortisol does not rise to expected levels. But most serum cortisol is bound to corticosteroid-binding globulin and albumin, and serum free cortisol (which typically is not measured) is the physiologically active component of total cortisol. In this study, researchers in Cleveland examined the relation between total and free cortisol levels in 66 critically ill patients, most of whom were in intensive care units.

Among 36 patients with serum albumin levels of 2.5 g/dL or lower (group 1), 1-hour cosyntropin stimulation tests revealed inadequate total cortisol responses in 14. In contrast, all 30 patients with serum albumin levels higher than 2.5 g/dL (group 2) had normal total cortisol responses to cosyntropin stimulation. However, median free cortisol levels -- both at baseline and after stimulation -- were virtually identical in the both patient groups and were substantially higher than levels in healthy volunteers.

Comment: These findings raise questions about the interpretation of serum total cortisol levels in critically ill patients: In hypoproteinemic patients with reduced binding globulin and albumin, physiologically active serum free cortisol levels typically were elevated even when total cortisol levels were not. Until serum free cortisol levels can be measured routinely, and until further studies determine exactly which critically ill patients truly have inadequate adrenal reserves, the authors suggest that decisions to give supplemental steroid therapy should be based not only on total cortisol measurements but also on clinical judgment.

— Allan S. Brett, MD

Published in Journal Watch General Medicine April 23, 2004

Citation(s):

Hamrahian AH et al. Measurements of serum free cortisol in critically ill patients. N Engl J Med 2004 Apr 15; 350:1629-38.

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