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Previous Volume 350:1629-1638 April 15, 2004 Number 16 Next

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ABSTRACT

Background Because more than 90 percent of circulating cortisol in human serum is protein-bound, changes in the binding proteins can alter measured serum total cortisol concentrations without influencing free concentrations of this hormone. We investigated the effect of decreased amounts of cortisol-binding proteins on serum total and free cortisol concentrations during critical illness, when glucocorticoid secretion is maximally stimulated.

Methods Base-line serum total cortisol, cosyntropin-stimulated serum total cortisol, aldosterone, and free cortisol concentrations were measured in 66 critically ill patients and 33 healthy volunteers in groups that were similar with regard to sex and age. Of the 66 patients, 36 had hypoproteinemia (albumin concentration, 2.5 g per deciliter or less), and 30 had near-normal serum albumin concentrations (above 2.5 g per deciliter).

Results Base-line and cosyntropin-stimulated serum total cortisol concentrations were lower in the patients with hypoproteinemia than in those with near-normal serum albumin concentrations (P<0.001). However, the mean (±SD) base-line serum free cortisol concentrations were similar in the two groups of patients (5.1±4.1 and 5.2±3.5 µg per deciliter [140.7±113.1 and 143.5±96.6 nmol per liter]) and were several times higher than the values in controls (0.6±0.3 µg per deciliter [16.6±8.3 nmol per liter], P<0.001 for both comparisons). Cosyntropin-stimulated serum total cortisol concentrations were subnormal (18.5 µg per deciliter [510.4 nmol per liter] or less) in 14 of the patients, all of whom had hypoproteinemia. In all 66 patients, including these 14 who had hypoproteinemia, the base-line and cosyntropin-stimulated serum free cortisol concentrations were high-normal or elevated.

Conclusions During critical illness, glucocorticoid secretion markedly increases, but the increase is not discernible when only the serum total cortisol concentration is measured. In this study, nearly 40 percent of critically ill patients with hypoproteinemia had subnormal serum total cortisol concentrations, even though their adrenal function was normal. Measuring serum free cortisol concentrations in critically ill patients with hypoproteinemia may help prevent the unnecessary use of glucocorticoid therapy.

Source Information

From the Division of Clinical and Molecular Endocrinology, University Hospitals of Cleveland and Case Western Reserve University, Cleveland.

Address reprint requests to Dr. Arafah at the Division of Clinical and Molecular Endocrinology, University Hospitals of Cleveland, 11100 Euclid Ave., Cleveland, OH 44106, or at bxa{at}po.cwru.edu.

Full Text of this Article

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Free Cortisol and Critically Ill Patients
Khan T., Kupfer Y., Tessler S., Polderman K. H., van Zanten A., Girbes A. R.J., Jackson W. L. Jr., Shorr A. F., Vogeser M., Briegel J., Arafah B. M., Loriaux L.
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N Engl J Med 2004; 351:395-397, Jul 22, 2004. Correspondence

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