A nonlabeled method to evaluate cortisol production rate by modeling plasma CBG-free cortisol disposition

This study aimed to develop a nonlabeled method for the measurement of cort isol production rate to evaluate adrenal function. The cortisol production rate determination requires that of cortisol clearance, which is not a para meter but a variable resulting from the saturable binding of cortisol to co rticosteroid-binding globulin (CBG). Our method is based on evaluation of t he plasma clearance of the CBG-free cortisol fraction. This parameter was e valuated from a pharmacokinetic model of total plasma cortisol disposition that takes into account specific binding of the corticoid to CBG in the pla sma. We have shown that the CBG-free cortisol kinetics and CBG-binding para meters thus evaluated are not statistically different from those obtained b y the radioisotopic method and equilibrium dialysis, suggesting that the pl asma CBG-free cortisol clearance is independent of the total plasma cortiso l concentrations and represents the actual parameter of cortisol eliminatio n. We validated this modeling approach by using it to calculate the in vivo entry rate of cortisol mimicked by the perfusion of cortisol at a known ra te.