Estimation of Maximal Cortisol Secretion Rate in Healthy Humans

Context: Cortisol secretion is related to ACTH concentration by a sigmoidal dose-response curve, in which high ACTH concentrations drive maximal cortisol secretion rates (CSRmax). Objective: We sought to estimate CSRmax and free cortisol half-life in healthy humans(n = 21) using numerical methods applied to data acquired during cosyntropin (250 mu g) stimulation. We also evaluated the effect of overnight dexamethasone (DEX; 1 mg) vs. placebo on estimates of CSRmax and free cortisol half-life. Design: This study was a double-blind, placebo-controlled, randomized order of overnight DEX vs. placebo, cosyntropin (250 mu g) stimulation with frequent serum cortisol sampling and computer-assisted numerical analysis. Setting: The study was conducted at a single academic medical center. Participants: Twenty-one healthy adult subjects (15 females and six males), mean aged 46 yr, participated in the study. Intervention: Intervention in the study included DEX vs. placebo pretreatment, cosyntropin (250 mu g) iv with frequent cortisol sampling. Main Outcome Measures: CSRmax and free cortisol half-life estimates, R-2 for goodness of fit, were measured. Results: Mean +/- SD CSRmax was 0.44 +/- 0.13 nM/second, with free cortisol half-life of 2.2 +/- 1.1 min. DEX did not significantly affect estimates of CSRmax or free cortisol half-life. Our model accounts for most of the variability of measured cortisol concentrations(overall R-2 = 90.9 +/- 11.0%) and was more accurate (P = 0.004) during DEX suppression (R-2 = 94.6 +/- 4.6%) compared with placebo (R-2 = 87.2 +/- 8.7%). Conclusions: Application of a mass-action model under conditions of cosyntropin stimulation provides a relatively simple method for estimation CSRmax that accurately predicts measured cortisol concentrations. DEX administration did not significantly affect estimates of CSRmax or free cortisol half-life. (J Clin Endocrinol Metab 97: 1285-1293, 2012)