Department of Public Health and Clinical Medicine, Umeå University, Umeå, Sweden.
Department of Medical Biosciences, Clinical Chemistry, Umeå University, Umeå, Sweden.
Eur J Endocrinol. 2020 Jun;182(6):569-582. doi: 10.1530/EJE-19-0872.
The challenge of diagnosing Cushing's syndrome (CS) calls for high precision biochemical screening. This study aimed to establish robust reference intervals for, and compare the diagnostic accuracy of, salivary cortisol and cortisone in late-night samples and after a low-dose (1 mg) dexamethasone suppression test (DST).
Saliva samples were collected at 08:00 and 23:00 h, and at 08:00 h, after a DST, from 22 patients with CS and from 155 adult reference subjects. We also collected samples at 20:00 and 22:00 h from 78 of the reference subjects. Salivary cortisol and cortisone were analysed with liquid chromatography-tandem mass spectrometry. The reference intervals were calculated as the 2.5th and 97.5th percentiles of the reference population measurements. Diagnostic accuracies of different tests were compared, based on areas under the receiver-operating characteristic curves.
The upper reference limits of salivary cortisol and cortisone at 23:00 h were 3.6 nmol/L and 13.5 nmol/L, respectively. Using these reference limits, CS was detected with a sensitivity (95% CI) of 90% (70-99%) and specificity of 96% (91-98%) for cortisol, and a 100% (84-100%) sensitivity and 95% (90-98%) specificity for cortisone. After DST, cortisol and cortisone upper reference limits were 0.79 nmol/L and 3.5 nmol/L, respectively. CS was detected with 95% (75-100%) sensitivity and 96% (92-99%) specificity with cortisol, and 100% (83-100%) sensitivity and 94% (89-97%) specificity with cortisone. No differences in salivary cortisol or cortisone levels were found between samples collected at 22:00 and 23:00 h.
Salivary cortisol and cortisone in late-night samples and after DST showed high accuracy for diagnosing CS, salivary cortisone being slightly, but significantly better.
库欣综合征（CS）的诊断极具挑战性，需要高度精确的生化筛查。本研究旨在建立可靠的唾液皮质醇和皮质酮的参考区间，并比较深夜样本和小剂量（1mg）地塞米松抑制试验（DST）后这两种物质的诊断准确性。
22 例 CS 患者和 155 例成人参考对象在 08:00 和 23:00 时以及 DST 后 08:00 时采集唾液样本，78 例参考对象还在 20:00 和 22:00 时采集样本。采用液相色谱-串联质谱法分析唾液皮质醇和皮质酮。参考区间计算为参考人群测量值的第 2.5 和 97.5 百分位数。根据受试者工作特征曲线下的面积比较不同检测方法的诊断准确性。
23:00 时唾液皮质醇和皮质酮的参考上限分别为 3.6 nmol/L 和 13.5 nmol/L。使用这些参考限，皮质醇诊断 CS 的敏感性（95%CI）为 90%（70-99%），特异性为 96%（91-98%），皮质酮的敏感性为 100%（84-100%），特异性为 95%（90-98%）。DST 后，皮质醇和皮质酮的参考上限分别为 0.79 nmol/L 和 3.5 nmol/L。皮质醇诊断 CS 的敏感性为 95%（75-100%），特异性为 96%（92-99%），皮质酮的敏感性为 100%（83-100%），特异性为 94%（89-97%）。22:00 和 23:00 采集的唾液样本中皮质醇和皮质酮水平无差异。
深夜样本和 DST 后唾液皮质醇和皮质酮对 CS 的诊断准确性很高，皮质酮略高，但差异有统计学意义。
