Medical Service 111/Endocrinology, New Mexico Veterans Affairs Healthcare System, 1501 San Pedro Boulevard SE, Albuquerque, New Mexico 87108, USA.
J Clin Endocrinol Metab. 2012 Apr;97(4):1285-93. doi: 10.1210/jc.2011-2227. Epub 2012 Feb 15.
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)).
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.
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.
The study was conducted at a single academic medical center.
Twenty-one healthy adult subjects (15 females and six males), mean aged 46 yr, participated in the study.
Intervention in the study included DEX vs. placebo pretreatment, cosyntropin (250 μg) iv with frequent cortisol sampling.
CSR(max) and free cortisol half-life estimates, R² for goodness of fit, were measured.
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%).
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.
皮质醇的分泌与促肾上腺皮质激素（ACTH）浓度呈S 型剂量反应曲线相关，其中高浓度的 ACTH 驱动最大皮质醇分泌率（CSR(max)）。
我们旨在使用数值方法估计健康人体的 CSR(max)和游离皮质醇半衰期，该方法应用于促皮质素（250μg）刺激期间获得的数据。我们还评估了过夜给予地塞米松（DEX；1mg）与安慰剂对 CSR(max)和游离皮质醇半衰期估计的影响。
这是一项双盲、安慰剂对照、随机序贯的过夜 DEX 与安慰剂、促皮质素（250μg）刺激、频繁血清皮质醇采样和计算机辅助数值分析的研究。
该研究在一个单一的学术医疗中心进行。
21 名健康成年受试者（15 名女性和 6 名男性），平均年龄为 46 岁，参与了这项研究。
研究中的干预措施包括 DEX 与安慰剂预处理、静脉注射促皮质素（250μg），并频繁采样皮质醇。
测量 CSR(max)和游离皮质醇半衰期的估计值、拟合优度的 R²。
平均±标准差 CSR(max)为 0.44±0.13nm/秒，游离皮质醇半衰期为 2.2±1.1 分钟。地塞米松并未显著影响 CSR(max)或游离皮质醇半衰期的估计值。我们的模型解释了测量皮质醇浓度的大部分变异性（总体 R²=90.9±11.0%），并且在 DEX 抑制时（R²=94.6±4.6%）比安慰剂（R²=87.2±8.7%）更准确（P=0.004）。
在促皮质素刺激条件下应用质量作用模型为估计 CSR(max)提供了一种相对简单的方法，该方法能够准确预测测量的皮质醇浓度。地塞米松给药并未显著影响 CSR(max)或游离皮质醇半衰期的估计值。
