Estimation of maximal cortisol secretion rate in healthy humans

J Clin Endocrinol Metab. 2012 Apr;97(4):1285-93. doi: 10.1210/jc.2011-2227. Epub 2012 Feb 15.


Context: Cortisol secretion is related to ACTH concentration by a sigmoidal dose-response curve, in which high ACTH concentrations drive maximal cortisol secretion rates (CSR(max)).

Objective: We sought to estimate CSR(max) and free cortisol half-life in healthy humans (n = 21) using numerical methods applied to data acquired during cosyntropin (250 μg) stimulation. We also evaluated the effect of overnight dexamethasone (DEX; 1 mg) vs. placebo on estimates of CSR(max) and free cortisol half-life.

Design: This study was a double-blind, placebo-controlled, randomized order of overnight DEX vs. placebo, cosyntropin (250 μg) 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 μg) iv with frequent cortisol sampling.

Main outcome measures: CSR(max) and free cortisol half-life estimates, R² for goodness of fit, were measured.

Results: Mean ± sd CSR(max) 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 CSR(max) or free cortisol half-life. Our model accounts for most of the variability of measured cortisol concentrations (overall R² = 90.9 ±11.0%) and was more accurate (P = 0.004) during DEX suppression (R² = 94.6 ± 4.6%) compared with placebo (R² = 87.2 ± 8.7%).

Conclusions: Application of a mass-action model under conditions of cosyntropin stimulation provides a relatively simple method for estimation CSR(max) that accurately predicts measured cortisol concentrations. DEX administration did not significantly affect estimates of CSR(max) or free cortisol half-life.

Publication types

  • Randomized Controlled Trial
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Adrenal Cortex / drug effects
  • Adrenal Cortex / metabolism*
  • Adrenal Cortex Function Tests*
  • Adult
  • Cosyntropin
  • Dexamethasone
  • Double-Blind Method
  • Female
  • Glucocorticoids
  • Half-Life
  • Humans
  • Hydrocortisone / blood
  • Hydrocortisone / metabolism*
  • Kinetics
  • Male
  • Middle Aged
  • Models, Biological*
  • Reproducibility of Results


  • Glucocorticoids
  • Cosyntropin
  • Dexamethasone
  • Hydrocortisone