Richard I Dorin1, Zhi Qiao, Clifford R Qualls, Frank K Urban. 1. Medical Service 111/Endocrinology, New Mexico Veterans Affairs Healthcare System, 1501 San Pedro Boulevard SE, Albuquerque, New Mexico 87108, USA. rdorin@salud.unm.edu
Abstract
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.
RCT Entities:
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.
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