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Published ahead of print on August 16, 2007, doi:10.1164/rccm.200702-307OC
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American Journal of Respiratory and Critical Care Medicine Vol 176. pp. 913-920, (2007)
© 2007 American Thoracic Society
doi: 10.1164/rccm.200702-307OC


Original Article

Free and Total Cortisol Levels as Predictors of Severity and Outcome in Community-acquired Pneumonia

Mirjam Christ-Crain1,4, Daiana Stolz2, Sukhdeep Jutla1, Orestes Couppis1, Christian Müller3, Roland Bingisser3, Philipp Schuetz4, Michael Tamm2, Ray Edwards5, Beat Müller4 and Ashley B. Grossman1

1 Department of Endocrinology, William Harvey Research Institute, Barts and The London, Queen Mary's School of Medicine and Dentistry, London, United Kingdom; 2 Department of Pneumology, 3 Department of Internal Medicine, and 4 Department of Endocrinology, University Hospital Basel, Basel, Switzerland; and 5 NETRIA, St. Bartholomew's Hospital, London, United Kingdom

Correspondence and requests for reprints should be addressed to Mirjam Christ-Crain, M.D., University Hospital, Petersgraben 4, CH-4031 Basel, Switzerland. E-mail: m.christ-crain{at}unibas.ch

Rationale: High cortisol levels are of prognostic value in sepsis. The predictive value of cortisol in pneumonia is unknown. Routinely available assays measure serum total cortisol (TC) and not free cortisol (FC). Whether FC concentrations better reflect outcome is uncertain.

Objectives: To investigate the predictive value of TC and FC in community-acquired pneumonia (CAP).

Methods: Preplanned subanalysis of a prospective intervention study in 278 patients presenting to the emergency department with CAP.

Measurements and Main Results: TC, FC, procalcitonin, C-reactive protein, leukocytes, clinical variables, and the pneumonia severity index (PSI) were measured. The major outcome measures were PSI and survival. TC and FC, but not C-reactive protein or leukocytes, increased with increasing severity of CAP according to the PSI (P < 0.001). TC and FC levels on presentation in patients who died during follow-up were significantly higher as compared with levels in survivors. In a receiver operating characteristic analysis to predict survival, the area under the receiver operating characteristic curve (AUC) was 0.76 (95% confidence interval, 0.70–0.81) for TC and 0.69 (0.63–0.74) for FC. This was similar to the AUC of the PSI (0.76 [0.70–0.81]), and better as compared with C-reactive protein, procalcitonin, or leukocytes. In univariate analysis, only TC, FC, and the PSI were predictors of death. In multivariate analysis, the predictive potential of TC equaled the prognostic power of PSI points.

Conclusions: Cortisol levels are predictors of severity and outcome in CAP to a similar extent to the PSI, and are better than routinely measured laboratory parameters. In CAP, the prognostic accuracy of FC is not superior to TC.

Clinical trial registered with www.controlled-trials.com (ISRCTN04176397).

Key Words: pneumonia • cortisol • prognosis


AT A GLANCE COMMENTARY

Scientific Knowledge on the Subject
High cortisol levels are of prognostic value in sepsis. The predictive value of cortisol in pneumonia is not known. Whether the free or total cortisol concentration better reflects outcome is uncertain.

What This Study Adds to the Field
Total and free cortisol levels are independent predictors of severity and outcome of pneumonia, in contrast to routinely measured laboratory parameters. The prognostic accuracy of free cortisol is not superior to that of total cortisol.

 



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