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Published ahead of print on September 14, 2006, doi:10.1164/rccm.200509-1369OC

Am. J. Respir. Crit. Care Med., Volume 174, Number 12, December 2006, 1319-1326

A more recent version of this article appeared on December 15, 2006
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Submitted on September 3, 2005
Accepted on September 8, 2006

Diagnosis of Adrenal Insufficiency in Severe Sepsis and Septic Shock

Djillali Annane1*, Virginie Maxime1, Fidaa Ibrahim2, Jean Claude Alvarez3, Emuri Abe3, and Philippe Boudou2

1 Service de Reanimation, Hopital Raymond Poincare, Faculte de Medecine Paris Ile de France Ouest, University of Versailles SQY, Assistance Publique Hopitaux de Paris, Garches, France, 2 Service de Biochimie-pharmacologie, Hopital Raymond Poincare (AP-HP), Faculte de Medecine Paris Ile de France Ouest, University of Versailles SQY, Assistance Publique Hopitaux de Paris, Garches, France, 3 Service de Biochimie Hormonale, Hopital Saint Louis, Faculte de Medecine Saint Louis Lariboisiere, University of Paris VII, Assistance Publique Hopitaux de Paris, Paris, France

* To whom correspondence should be addressed. E-mail: djillali.annane{at}rpc.aphp.fr.

Rationale. Diagnosis of adrenal insufficiency in critically ill patients has relied on random or cosyntropin-stimulated cortisol levels, and has not been corroborated by more accurate diagnostic standard. Objective. We used the overnight metyrapone stimulation test to investigate the diagnostic value of the standard cosyntropin-stimulation test, and the prevalence of sepsis-associated adrenal insufficiency. Methods. This was an inception cohort study. Measurements and results. In two consecutive septic cohorts (n=61 and n=40), in 44 nonseptic patients and in 32 healthy volunteers, we measured (i) before and after cosyntropin stimulation serum cortisol, albumin and corticosteroid-binding globulin levels and (ii) before and after an overnight metyrapone stimulation serum corticotropin, cortisol, 11{beta}-deoxycortisol levels. Adrenal insufficiency was defined by post-metyrapone serum 11{beta}-deoxycortisol levels <7µg/dl. There were more septic patients (31/61:59% of original septic cohort and 24/40: 60% of validation septic cohort) who met criteria for adrenal insufficiency than among the non-septic patients (3/44:7%) (p<0.001 for both comparisons). Baseline cortisol <10µg/dl, delta cortisol <9µg/dl and free cortisol <2µg/dl had a positive likelihood ratio equal to infinite, 8.46 (95% CI: 1.19-60.25), and 9.50 (1.05-9.54), respectively. The best predictor of adrenal insufficiency (as defined by metyrapone testing) was baseline cortisol ≤10µg/dl or delta cortisol <9µg/dl. The best predictors of normal adrenal response were cosyntropin-stimulated cortisol ≥44µg/dl, and delta cortisol ≥16.8 µg/dl. Conclusions. In sepsis, adrenal insufficiency is likely when baseline cortisol levels are less than 10µg/dl or delta cortisol is less than 9µg/dl, and unlikely when cosyntropin-stimulated cortisol level is equal or greater than 44µg/dl or delta cortisol is equal or greater than 16.8µg/dl.
Key words: Metyrapone, cortisol, septicemia, corticotropin




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