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Rosa M. Estrada-Y-Martin, MD, FCCP
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From the Divisions of Pulmonary, Critical Care and Sleep Medicine, Department of Medicine, University of Texas-Houston Medical School.

Correspondence to: Rosa M. Estrada-Y-Martin, MD, FCCP, Divisions of Pulmonary, Critical Care and Sleep Medicine, Department of Medicine, University of Texas-Houston Medical School, 6431 Fannin, Ste 1.266, Houston, TX 77030; e-mail: rosa.m.estrada.y.martin@uth.tmc.edu


Financial/nonfinancial disclosures: The authors have reported to CHEST that no potential conflicts of interest exist with any companies/organizations whose products or services may be discussed in this article.

Reproduction of this article is prohibited without written permission from the American College of Chest Physicians (www.chestjournal.org/site/misc/reprints.xhtml).


© 2012 American College of Chest Physicians


Chest. 2012;141(1):273-274. doi:10.1378/chest.11-2159
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To the Editor:

I welcome the comments of Dr Mallat regarding our article.1 Although I agree with the comments, the purpose of our study was not only to correlate free serum cortisol and salivary cortisol but also to create a regression equation that would allow for the prediction of free serum cortisol. The determination of total serum cortisol is a poor surrogate of free serum cortisol because it includes bound and unbound hormone and only free serum cortisol is functionally active. Salivary cortisol is a better surrogate as demonstrated by our study.1 Ideally, we would like to know the free serum cortisol concentration in patients with septic shock to decide whether replacement is necessary; however, the test is technically difficult and time consuming (see the “Discussion” section in original article1). Even more important is the observation that the degree of agreement is better when the free serum cortisol concentration is low, which is more relevant to considering corticosteroid replacement (see the “Discussion” section in original article1).

We have constructed three Bland-Altman plots for review. The first plot (Fig 1) is the relationship between free serum cortisol and salivary cortisol. The second plot (Fig 2) is the relationship between salivary cortisol ≤ 2.5 μg/dL and free serum cortisol ≤ 2.0 μg/dL. We chose those values based on Annane et al,2 suggesting that a free serum cortisol of <2.0 μg/dL may represent true adrenal insufficiency after metyrapone stimulation testing in severe sepsis and septic shock; also, per our study, mean salivary cortisol is mildly elevated compared with free serum cortisol. Finally, the third plot (Fig 3) shows the relationship between free serum cortisol and total serum cortisol.

Figure Jump LinkFigure 1. Bland-Altman plot between salivary cortisol and free serum cortisol (38 patients). Limits of agreement, −3.045-4.090; mean difference, 0.523; 95% CI, −0.064-1.109; range, 0.180-11.040; Pitman test r, 0.702; P = .001.Grahic Jump Location
Figure Jump LinkFigure 2. Bland-Altman plot between salivary cortisol ≤ 2.5 μg/dL and free serum cortisol ≤ 2.0 μg/dL (29 patients). Limits of agreement, −1.577-1.657; mean difference, 0.040; 95% CI, −0.268-0.347; range, 0.180-2.495; Pitman test r, −0.107; P =0.583.Grahic Jump Location
Figure Jump LinkFigure 3. Bland-Altman plot between total serum cortisol and free serum cortisol (57 patients). Limits of agreement, −33.966 to −4.596; mean difference, −19.281; 95% CI, −21.229 to −17.333; range, 2.495-25.825; Pitman test r, −0.981; P =0.001.Grahic Jump Location

Until free serum cortisol concentration can be obtained fast and on a daily basis, salivary cortisol approximates better to the free hormone concentration than total serum cortisol, and it may be useful to decide replacement therapy. However, surrogate tests are not perfect.

Estrada-Y-Martin RM, Orlander PR. Salivary cortisol can replace free serum cortisol measurements in patients with septic shock. Chest. 2011;1405:1216-1222 [PubMed] [CrossRef]
 
Annane D, Maxime V, Ibrahim F, Alvarez JC, Abe E, Boudou P. Diagnosis of adrenal insufficiency in severe sepsis and septic shock. Am J Respir Crit Care Med. 2006;17412:1319-1326 [PubMed]
 

Figures

Figure Jump LinkFigure 1. Bland-Altman plot between salivary cortisol and free serum cortisol (38 patients). Limits of agreement, −3.045-4.090; mean difference, 0.523; 95% CI, −0.064-1.109; range, 0.180-11.040; Pitman test r, 0.702; P = .001.Grahic Jump Location
Figure Jump LinkFigure 2. Bland-Altman plot between salivary cortisol ≤ 2.5 μg/dL and free serum cortisol ≤ 2.0 μg/dL (29 patients). Limits of agreement, −1.577-1.657; mean difference, 0.040; 95% CI, −0.268-0.347; range, 0.180-2.495; Pitman test r, −0.107; P =0.583.Grahic Jump Location
Figure Jump LinkFigure 3. Bland-Altman plot between total serum cortisol and free serum cortisol (57 patients). Limits of agreement, −33.966 to −4.596; mean difference, −19.281; 95% CI, −21.229 to −17.333; range, 2.495-25.825; Pitman test r, −0.981; P =0.001.Grahic Jump Location

Tables

References

Estrada-Y-Martin RM, Orlander PR. Salivary cortisol can replace free serum cortisol measurements in patients with septic shock. Chest. 2011;1405:1216-1222 [PubMed] [CrossRef]
 
Annane D, Maxime V, Ibrahim F, Alvarez JC, Abe E, Boudou P. Diagnosis of adrenal insufficiency in severe sepsis and septic shock. Am J Respir Crit Care Med. 2006;17412:1319-1326 [PubMed]
 
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