title: Estimation of maximal cortisol secretion rate in healthy humans.
abstract: BACKGROUND
  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.
  
  
  METHODS
  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.
  
  
  METHODS
  The study was conducted at a single academic medical center.
  
  
  METHODS
  Twenty-one healthy adult subjects (15 females and six males), mean aged 46 yr, participated in the study.
  
  
  METHODS
  Intervention in the study included DEX vs. placebo pretreatment, cosyntropin (250 μg) iv with frequent cortisol sampling.
  
  
  METHODS
  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.
authors.affiliation: Medical Service 111/Endocrinology, New Mexico Veterans Affairs Healthcare System, 1501 San Pedro Boulevard SE, Albuquerque, New Mexico 87108, USA. rdorin@salud.unm.edu
authors.forename: Richard I
authors.initials: RI
authors.lastname: Dorin
authors.forename: Zhi
authors.initials: Z
authors.lastname: Qiao
authors.forename: Clifford R
authors.initials: CR
authors.lastname: Qualls
authors.forename: Frank K
authors.initials: FK
authors.lastname: Urban
mesh_terms: D000302:Adrenal Cortex / Q000187:drug effects / Q000378:metabolism*; D000304:Adrenal Cortex Function Tests; D000328:Adult; D003366:Cosyntropin; D003907:Dexamethasone; D004311:Double-Blind Method; D005260:Female; D005938:Glucocorticoids; D006207:Half-Life; D006801:Humans; D006854:Hydrocortisone / Q000097:blood / Q000378:metabolism*; D007700:Kinetics; D008297:Male; D008875:Middle Aged; D008954:Models, Biological; D015203:Reproducibility of Results
chemical_list: D005938:Glucocorticoids; D003366:Cosyntropin; D003907:Dexamethasone; D006854:Hydrocortisone