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Type: Journal article
Title: Validation of a simple method of estimating plasma free cortisol: Role of cortisol binding to albumin
Author: Dorin, R.
Pai, H.
Ho, J.
Lewis, J.
Torpy, D.
Urban, F.
Qualls, C.
Citation: Clinical Biochemistry, 2008; 42(1-2):64-71
Publisher: Pergamon-Elsevier Science Ltd
Issue Date: 2008
ISSN: 0009-9120
Statement of
Richard I. Dorin, Hemanth K. Pai, Jui T. Ho, John G. Lewis, David J. Torpy, Frank K. Urban III and Clifford R. Qualls
Abstract: <h4>Objectives</h4>To develop, optimize, and validate a generalized mass action, equilibrium solution that incorporates measured concentrations of albumin as well as cortisol binding globulin (CBG) to estimate free cortisol.<h4>Design and methods</h4>Free cortisol was estimated by Coolens method or by cubic equilibrium equation and compared to measured free cortisol, determined by ultrafiltration method, in subjects with septic shock (n=45), sepsis (n=19), and healthy controls (n=10) at 0, 30, and 60 min following administration of cosyntropin (250 mcg). The data set also included repeat testing in 30 subjects following recovery from sepsis/septic shock. The equilibrium dissociation constant for cortisol binding to albumin (K(A)) was optimized by non-linear regression. The cubic equilibrium solution was also used to model the influence of cortisol, CBG, and albumin concentration on free cortisol.<h4>Results</h4>Compared to measured free cortisol, the cubic solution, using an optimized K(A) of 137,800 nM, was less biased than Coolens solution, with mean percent error of -23.0% vs. -41.1% (paired t test, P<0.001). Standard deviation values were also significantly lower (Wilks' test, P<0.001) for the cubic solution (SD 35.8% vs. 40.8% for cubic vs. Coolens, respectively). Modeling studies using the cubic solution suggest an interaction effect by which low concentrations of CBG and albumin contribute to a greater increase in free cortisol than the sum of their independent effects.<h4>Conclusions</h4>Mass action solutions that incorporate the measured concentration of albumin as well as CBG provide a reasonably accurate estimate of free cortisol that generalizes to conditions of health as well as a setting of hypercortisolism and low CBG and albumin concentrations associated with septic shock. Modeling studies emphasize the significant contribution of albumin deficiency and albumin-bound cortisol under conditions of CBG-deficiency, and identify a synergistic effect by which combined CBG and albumin deficiency contribute to elevation of free cortisol in septic shock.
Keywords: Free cortisol
Mass action
Cubic equation
Septic shock
Dissociation constant
Corticosteroid binding globulin
Description: Copyright © 2008 Published by Elsevier Inc.
DOI: 10.1016/j.clinbiochem.2008.09.115
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