Kannankeril Joshua, Carroll Ty, Findling James W, Javorsky Bradley, Gunsolus Ian L, Phillips Jonathan, Raff Hershel
Division of Endocrinology and Molecular Medicine, Department of Medicine, Medical College of Wisconsin, Milwaukee, Wisconsin.
Endocrinology Center and Clinics, Medical College of Wisconsin, Milwaukee, Wisconsin.
J Endocr Soc. 2020 Jul 24;4(10):bvaa107. doi: 10.1210/jendso/bvaa107. eCollection 2020 Oct 1.
Late-night salivary cortisol (LNSC) measured by enzyme immunoassay (EIA-F) is a first-line screening test for Cushing syndrome (CS) with a reported sensitivity and specificity of >90%. However, liquid chromatography-tandem mass spectrometry, validated to measure salivary cortisol (LCMS-F) and cortisone (LCMS-E), has been proposed to be superior diagnostically.
Prospectively evaluate the diagnostic performance of EIA-F, LCMS-F, and LCMS-E in 1453 consecutive late-night saliva samples from 705 patients with suspected CS.
Patients grouped by the presence or absence of at least one elevated salivary steroid result and then subdivided by diagnosis.
We identified 283 patients with at least one elevated salivary result; 45 had an established diagnosis of neoplastic hypercortisolism (CS) for which EIA-F had a very high sensitivity (97.5%). LCMS-F and LCMS-E had lower sensitivity but higher specificity than EIA-F. EIA-F had poor sensitivity (31.3%) for adrenocorticotropic hormone (ACTH)-independent CS (5 patients with at least 1 and 11 without any elevated salivary result). In patients with Cushing disease (CD), most nonelevated LCMS-F results were in patients with persistent/recurrent CD; their EIA-F levels were lower than in patients with newly diagnosed CD.
Since the majority of patients with ≥1 elevated late-night salivary cortisol or cortisone result did not have CS, a single elevated level has poor specificity and positive predictive value. LNSC measured by EIA is a sensitive test for ACTH-dependent Cushing syndrome but not for ACTH-independent CS. We suggest that neither LCMS-F nor LCMS-E improves the sensitivity of late-night EIA-F for CS.
通过酶免疫测定法（EIA-F）测量的午夜唾液皮质醇（LNSC）是库欣综合征（CS）的一线筛查试验，报告的敏感性和特异性>90%。然而，已被验证用于测量唾液皮质醇（LCMS-F）和可的松（LCMS-E）的液相色谱-串联质谱法被认为在诊断上更具优势。
前瞻性评估EIA-F、LCMS-F和LCMS-E在705例疑似CS患者的1453份连续午夜唾液样本中的诊断性能。
根据是否至少有一项唾液类固醇结果升高对患者进行分组，然后再根据诊断进行细分。
我们确定了283例至少有一项唾液结果升高的患者；45例已确诊为肿瘤性皮质醇增多症（CS），EIA-F对此具有非常高的敏感性（97.5%）。LCMS-F和LCMS-E的敏感性低于EIA-F，但特异性更高。EIA-F对促肾上腺皮质激素（ACTH）非依赖性CS的敏感性较差（31.3%）（5例至少有1项升高，11例无任何唾液结果升高）。在库欣病（CD）患者中，大多数LCMS-F结果未升高的患者为持续性/复发性CD患者；他们的EIA-F水平低于新诊断的CD患者。
由于大多数午夜唾液皮质醇或可的松结果至少有一项升高的患者没有CS，单一升高水平的特异性和阳性预测值较差。通过EIA测量的LNSC对ACTH依赖性库欣综合征是一项敏感试验，但对ACTH非依赖性CS不敏感。我们认为LCMS-F和LCMS-E均未提高午夜EIA-F对CS的敏感性。
