Abstract：
BACKGROUND: Salivary cortisol (sa-cortisol) and salivary cortisone (sa-cortisone) correlate well with serum cortisol (s-cortisol) but validated reference ranges for healthy individuals are lacking.
OBJECTIVE: To establish cutoff levels for sa-cortisol and cortisone following cosyntropin testing, and assess their diagnostic utility in adrenal insufficiency (AI).
METHODS: Steroids in saliva were assayed using liquid-chromatography tandem-mass-spectrometry (LCMS/MS) before and after administration of 250µg cosyntropin test in 128 healthy subjects (16 on oral estrogens) and 59 patients with suspected AI, of whom 26 were diagnosed with AI with conventional serum cortisol criteria. The cutoff level for AI was defined as the 2.5th centile in healthy subjects not receiving estrogens. Performance was evaluated by calculating diagnostic accuracy and analyzing receiver operating characteristic-curves.
RESULTS: The sa-cortisol cutoff 60 minutes after cosyntropin stimulation was 12.6 nmol/L (accuracy 89%, sensitivity 85%, and specificity 90%). Sa-cortisone and the sum of sa-cortisol and cortisone exhibited poorer diagnostic performance than sa-cortisol. The correlation between sa-cortisol and s-cortisol was best described by a model incorporating two regression lines (R2 = 0.80). Segmented regression analysis identified a breakpoint at sa-cortisol 9.7 nmol/L and s-cortisol 482 nmol/L, likely corresponding to saturation of cortisol binding globulin (CBG). Healthy subjects on oral estrogens demonstrated a linear agreement between s- and sa-cortisol through all measurements. Seventeen healthy subjects repeated the test, with similar outcome, but reproducibility in terms of intraclass coefficient and correlation was poor.
CONCLUSIONS: Sa-cortisol in cosyntropin-test has high diagnostic accuracy in detecting adrenal insufficiency, and is particularly useful in women on oral estrogens. A sa-cortisol > 12.6 nmol/L assayed with LCMS/MS 60 min after 250µg cosyntropin is normal.
OBJECTIVE: To establish cutoff levels for sa-cortisol and cortisone following cosyntropin testing, and assess their diagnostic utility in adrenal insufficiency (AI).
METHODS: Steroids in saliva were assayed using liquid-chromatography tandem-mass-spectrometry (LCMS/MS) before and after administration of 250µg cosyntropin test in 128 healthy subjects (16 on oral estrogens) and 59 patients with suspected AI, of whom 26 were diagnosed with AI with conventional serum cortisol criteria. The cutoff level for AI was defined as the 2.5th centile in healthy subjects not receiving estrogens. Performance was evaluated by calculating diagnostic accuracy and analyzing receiver operating characteristic-curves.
RESULTS: The sa-cortisol cutoff 60 minutes after cosyntropin stimulation was 12.6 nmol/L (accuracy 89%, sensitivity 85%, and specificity 90%). Sa-cortisone and the sum of sa-cortisol and cortisone exhibited poorer diagnostic performance than sa-cortisol. The correlation between sa-cortisol and s-cortisol was best described by a model incorporating two regression lines (R2 = 0.80). Segmented regression analysis identified a breakpoint at sa-cortisol 9.7 nmol/L and s-cortisol 482 nmol/L, likely corresponding to saturation of cortisol binding globulin (CBG). Healthy subjects on oral estrogens demonstrated a linear agreement between s- and sa-cortisol through all measurements. Seventeen healthy subjects repeated the test, with similar outcome, but reproducibility in terms of intraclass coefficient and correlation was poor.
CONCLUSIONS: Sa-cortisol in cosyntropin-test has high diagnostic accuracy in detecting adrenal insufficiency, and is particularly useful in women on oral estrogens. A sa-cortisol > 12.6 nmol/L assayed with LCMS/MS 60 min after 250µg cosyntropin is normal.
摘要：
背景：唾液皮质醇（sa-皮质醇）和唾液可的松（sa-可的松）与血清皮质醇（s-皮质醇）相关性良好，但缺乏针对健康个体的有效参考范围。
目的：为了确定α-皮质醇和可的松的截止水平，并评估其在肾上腺功能不全（AI）中的诊断效用。
方法：在128名健康受试者（16名口服雌激素）和59名疑似AI患者中，在250μgcosyntropin试验之前和之后，使用液相色谱-串联质谱法（LCMS/MS）测定唾液中的类固醇。其中26人被诊断为AI符合常规血清皮质醇标准。AI的截止水平定义为未接受雌激素的健康受试者的第2.5百分位数。通过计算诊断准确性和分析接收器工作特性曲线来评估性能。
结果：共合成素刺激后60分钟的sa-皮质醇截止值为12.6nmol/L（准确度为89％，灵敏度85%,和特异性90%)。Sa-可的松以及sa-皮质醇和可的松的总和显示出比sa-皮质醇更差的诊断性能。sa-皮质醇和s-皮质醇之间的相关性最好通过包含两个回归线（R2=0.80）的模型来描述。分段回归分析确定了sa-皮质醇9.7nmol/L和s-皮质醇482nmol/L的断点，可能对应于皮质醇结合球蛋白（CBG）的饱和度。通过所有测量，口服雌激素的健康受试者表现出s-和sa-皮质醇之间的线性一致性。17名健康受试者重复测试，结果相似,但在组内系数和相关性方面的可重复性较差。
结论：Sa-皮质醇在检测肾上腺功能不全方面具有较高的诊断准确性，对女性口服雌激素特别有用。在250μg共合成素后60分钟用LCMS/MS测定的sa-皮质醇>12.6nmol/L是正常的。
目的：为了确定α-皮质醇和可的松的截止水平，并评估其在肾上腺功能不全（AI）中的诊断效用。
方法：在128名健康受试者（16名口服雌激素）和59名疑似AI患者中，在250μgcosyntropin试验之前和之后，使用液相色谱-串联质谱法（LCMS/MS）测定唾液中的类固醇。其中26人被诊断为AI符合常规血清皮质醇标准。AI的截止水平定义为未接受雌激素的健康受试者的第2.5百分位数。通过计算诊断准确性和分析接收器工作特性曲线来评估性能。
结果：共合成素刺激后60分钟的sa-皮质醇截止值为12.6nmol/L（准确度为89％，灵敏度85%,和特异性90%)。Sa-可的松以及sa-皮质醇和可的松的总和显示出比sa-皮质醇更差的诊断性能。sa-皮质醇和s-皮质醇之间的相关性最好通过包含两个回归线（R2=0.80）的模型来描述。分段回归分析确定了sa-皮质醇9.7nmol/L和s-皮质醇482nmol/L的断点，可能对应于皮质醇结合球蛋白（CBG）的饱和度。通过所有测量，口服雌激素的健康受试者表现出s-和sa-皮质醇之间的线性一致性。17名健康受试者重复测试，结果相似,但在组内系数和相关性方面的可重复性较差。
结论：Sa-皮质醇在检测肾上腺功能不全方面具有较高的诊断准确性，对女性口服雌激素特别有用。在250μg共合成素后60分钟用LCMS/MS测定的sa-皮质醇>12.6nmol/L是正常的。
