Cortisol Levels May Predict CAP Outcome and Severity

Key Point

The prognostic accuracy of total and free cortisol levels to predict the severity and outcome of CAP is as high as the PSI and better than commonly measured laboratory parameters; free cortisol is not more accurate than total cortisol.

NEW ORLEANS—While high cortisol levels have predictive value in sepsis, little is known about the prognostic value of cortisol in community-acquired pneumonia (CAP) or whether free cortisol concentrations are better indicators than are total cortisol levels. Investigators have found that cortisol levels may predict the severity and outcome of CAP as effectively as the pneumonia severity index (PSI) does and are better than routinely measured laboratory parameters. However, the prognostic accuracy of free cortisol was not found to be better than total cortisol.

“According to our data, the simple measurement of total cortisol provides equivalent prognostic information as the complex 20-variable severity index,” Mirjam Christ-Crain, MD, Associate Professor of Endocrinology at the University Hospital in Basel, Switzerland, and colleagues stated. “This is remarkable. It therefore represents an additional and easy-to-determine prognostic tool.”

PREDICTIVE POWER FOR MORTALITY

The investigators analyzed data from 278 participants who presented with CAP at the emergency department of a Swiss university hospital. As CAP severity worsened, total cortisol and free cortisol levels increased. In PSI classes I through III, the mortality rate was 1.8%; in PSI class IV, the mortality rate was 16%, and in PSI class V, it was 21%. According to post hoc analyses, there was a significant difference in free cortisol levels, but not total cortisol levels, between PSI groups IV and V. While the gradual increase with PSI class was significant for procalcitonin, it was not significant for C-reactive protein or total leukocyte count.

Two patients were lost to follow-up; for the remaining 276 patients, the overall mortality rate was 11.2%. Total cortisol and free cortisol levels in patients who died during follow-up were significantly higher than levels in survivors. The prognostic accuracy of cortisol to predict mortality was better than that of C-reactive protein, leukocyte count, and procalcitonin, and it was comparable to that of the PSI score; total cortisol was more accurate than free cortisol. In addition, combining total cortisol with PSI tended to improve the prognostic accuracy of PSI alone.

PROBLEMS WITH PSI

Dr. Christ-Crain and colleagues noted that a clinician’s decision to admit a patient with CAP is dependent on numerous variables, and current routinely used clinical signs and laboratory parameters—such as C-reactive protein or leukocyte count—“are of only limited value to predict disease severity in CAP. Thus, clinical judgment alone can be misleading in estimating disease severity, thereby leading to under- as well as overestimation of the severity of CAP.”

The PSI had therefore been developed to address the need for prognostic scoring rules, but the classification score is not without limitations, the investigators pointed out. Drawbacks of the PSI include the division of continuous values (such as heart rate or oxygen saturation) into normal and abnormal values, and an estimated 10% intraobserver variation, with most patients being misclassified into the high-risk classes IV and V. Furthermore, the researchers explained that CAP patients with a low mortality risk who might be suitable for home management are best evaluated by the PSI.

“The major limitation for the routine use of the PSI, however, is its laborious calculation,” Dr. Christ-Crain and colleagues stated. “In another study validating the predictive potential of various indices in 731 patients with CAP, the PSI score could be calculated in only 70% of all patients, restricting its widespread adoption. The American Thoracic Society guidelines do not offer any algorithm for the clinical assessment of disease severity. In this context, there is a need for readily measurable parameters predicting the severity level and outcome of CAP.”

OTHER POTENTIAL MARKERS VERSUS CORTISOL

In the current study, C-reactive protein could not distinguish between different severities of CAP as defined by the PSI and was not a significant independent predictor of CAP outcome, despite reports supporting its use as a marker for predicting disease severity in pneumonia patients. Dr. Christ-Crain and colleagues noted that “C-reactive protein is a rather nonspecific marker of acute-phase inflammation, and is thus subject to the influence of many other factors.” In addition, while interleukin-6 (IL-6) is a key stimulator of hepatic C-reactive protein release and may be a useful marker in determining CAP severity, the “measurement of plasma cytokines such as IL-6 is, however, a difficult and cumbersome process, partly because of the short plasma half-life and the presence of blocking factors,” the study authors stated.

Although prior investigations have suggested that procalcitonin may serve as a useful marker of CAP disease severity, procalcitonin may be better as a diagnostic tool rather than as a prognostic instrument, the researchers said. As evidenced by current findings, however, total cortisol could function as a new indicator for high-risk CAP patients by allowing them to be targeted for more intensive therapy.

“As the combination of cortisol measurement and the PSI score tended to have an even higher prognostic accuracy, it is advisable to use several clinical and laboratory parameters, which may mirror different physiologic aspects, in the complex task of prognostic assessment and treatment decisions,” the investigators pointed out. Dr. Christ-Crain told Pulmonary Reviews that “intervention studies are needed to evaluate cortisol as a prognostic marker in pneumonia, [such as] to investigate whether cortisol can be used to guide hospitalization, ICU admission, or health care consumption.”

—John Merriman

Reference
Christ-Crain M, Stolz D, Jutla S, et al. Free and total cortisol levels as predictors of severity and outcome in community-acquired pneumonia. Am J Respir Crit Care Med. 2007;176(9):913-920.
Christ-Crain M, Morgenthaler NG, Stolz D, et al. Pro-adrenomedullin to predict severity and outcome in community-acquired pneumonia. Crit Care. 2006;10(3):R96.
Ewig S, de Roux A, Bauer T, et al. Validation of predictive rules and indices of severity for community acquired pneumonia. Thorax. 2004;59(5):421-427.
Masiá M, Gutiérrez F, Shum C, et al. Usefulness of procalcitonin levels in community-acquired pneumonia according to the patients outcome research team pneumonia severity index. Chest. 2005;128(4):2223-2229.
Müller B, Harbarth S, Stolz D. Diagnostic and prognostic accuracy of clinical and laboratory parameters in community-acquired pneumonia. BMC Infect Dis. 2007;7:10.

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