- Journal club critique
- Open Access
Free cortisol levels should not be used to determine adrenal responsiveness
© BioMed Central Ltd 2004
- Published: 13 December 2004
Hamrahian AH, Oseni TS, Arafah BM. Measurements of serum free cortisol in critically ill patients. NEJM. 2004;350:1629-38.
Because more than 90 percent of circulating cortisol in human serum is protein-bound, changes in binding proteins can alter measured serum total cortisol concentrations without influencing free concentrations of this hormone.
Patients with presumably normal adrenal function but decreased cortisol-binding proteins will have lower-than-expected concentrations of serum total cortisol but appropriately elevated free cortisol levels.
Measurement of serum free cortisol concentrations will identify patients with normal or even increased adrenal function, who, on the basis of low total cortisol concentrations, would otherwise have been incorrectly considered to have adrenal insufficiency.
Medical, surgical, and cardiac ICUs and general medical ward of a tertiary care U.S. academic medical center.
Patients and Measurements
Baseline serum total cortisol, cosyntropin-stimulated serum total cortisol, aldosterone, and free cortisol concentrations were measured in 66 critically ill patients with an APACHE score of 15 or higher, 33 healthy volunteers, and 7 patients with adrenal insufficiency secondary to hypopituitarism. Patients were further divided into two groups based on their serum albumin concentrations of ≤ 2.5 g/dL (low albumin group, n = 36) or >2.5 g/dL (normal albumin group, n = 30).
Baseline and cosyntropin-stimulated serum total cortisol concentrations were significantly lower in the low albumin group than the normal albumin group. However, serum free cortisol concentrations were similar in the two groups and were several times higher than the values in healthy controls. Fourteen of thirty-six (39%) low albumin patients had subnormal cosyntropin stimulated total cortisol concentrations, consistent with a traditional diagnosis of adrenal insufficiency. These same patients had high-normal or elevated serum free cortisol concentrations.
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.
Until CORTICUS is completed, we recommend that a) all patients in septic shock with ≤ 9 μg/dL total cortisol response to corticotropin stimulation receive low-dose corticosteroids, and b) free cortisol levels should not be used to determine adrenal responsiveness.
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