Corticosteroid-binding globulin influences kinetic parameters of plasma cortisol transport and clearance

In an accompanying study, we reported a very poor correlation between the magnitude of a continuous cortisol infusion in dexamethasone-suppressed adults and the resultant steady state plasma cortisol concentration (r2 = 0.13). The concentration of corticosteroid-binding globulin (CBG) was found to explain an additional 39% of the variance in cortisol response. We hypothesized that CBG might act by altering kinetic parameters of cortisol transport. According, the rate of cortisol disappearance (Kd), volume of distribution (V), and pool size (P) were determined after bolus injection of a stable isotope of cortisol in two groups of healthy female subjects with both normal and elevated CBG concentrations. The bolus studies were performed during continuous cortisol infusion and steady state conditions of plasma cortisol concentration. Two models were used to generate the kinetic parameters. The kinetic parameters thus generated were able to predict the known cortisol infusion rate with 4-16% error. The goodness of fit of modeled to experimental data was excellent in all cases (> 0.93). In both models, Kd had a negative correlation to the CBG concentration (P < 0.05), a negative correlation to the volume of distribution (P < 0.03), and a positive correlation (P < 0.03) to pool size. Excellent correlations were noted between both models in estimates of kinetic parameters (r2 = 0.82-0.97; P < 0.01). We conclude that CBG, in addition to its role of transport protein, plays an active role in determining the disposition of cortisol in humans.