Dorin Richard I, Pai Hemanth K, Ho Jui T, Lewis John G, Torpy David J, Urban Frank K, Qualls Clifford R
Medical Service, New Mexico VA Healthcare System, Albuquerque, NM 87108, USA.
Clin Biochem. 2009 Jan;42(1-2):64-71. doi: 10.1016/j.clinbiochem.2008.09.115. Epub 2008 Oct 17.
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.
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.
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.
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.
开发、优化并验证一种广义质量作用平衡溶液，该溶液纳入白蛋白以及皮质醇结合球蛋白（CBG）的测量浓度以估算游离皮质醇。
通过库伦斯方法或三次方平衡方程估算游离皮质醇，并将其与通过超滤法测定的游离皮质醇进行比较，研究对象为败血症休克患者（n = 45）、脓毒症患者（n = 19）以及健康对照者（n = 10），在给予促肾上腺皮质激素（250微克）后的0、30和60分钟进行测定。数据集还包括30名脓毒症/败血症休克康复患者的重复检测。通过非线性回归优化皮质醇与白蛋白结合的平衡解离常数（K(A)）。三次方平衡溶液还用于模拟皮质醇、CBG和白蛋白浓度对游离皮质醇的影响。
与测定的游离皮质醇相比，使用优化后的K(A)为137,800纳摩尔的三次方溶液偏差小于库伦斯溶液，平均百分比误差分别为 -23.0% 和 -41.1%（配对t检验，P < 0.001）。三次方溶液的标准差数值也显著更低（威尔克斯检验，P < 0.001）（三次方溶液的标准差为35.8%，库伦斯溶液为40.8%）。使用三次方溶液的模型研究表明存在一种相互作用效应，即低浓度的CBG和白蛋白对游离皮质醇增加的贡献大于其独立效应之和。
纳入白蛋白以及CBG测量浓度的质量作用溶液能够合理准确地估算游离皮质醇，适用于健康状况以及高皮质醇血症、与败血症休克相关的低CBG和白蛋白浓度的情况。模型研究强调了在CBG缺乏情况下白蛋白缺乏和白蛋白结合皮质醇的重要贡献，并确定了一种协同效应，即CBG和白蛋白联合缺乏导致败血症休克中游离皮质醇升高。
