Dynamic testing for differential diagnosis of ACTH-dependent Cushing Syndrome: a systematic review and meta-analysis

Objective
Diagnostic accuracy of testing currently used for differential diagnosis of Cushing’s disease (CD) vs ectopic adrenocorticotropic hormone (ACTH) secretion (EAS) is difficult to interpret. The present study aimed to identify and evaluate diagnostic accuracy of corticotropin-releasing hormone (CRH) test, desmopressin test, and high-dose dexamethasone suppression test (HDDST) when used to establish a CD or EAS diagnosis.
Design
This study is a systematic review of the literature and meta-analysis.
Methods
MEDLINE, OVID, and Web of Science databases were searched for articles published between the years 1990-2021. Articles included described at least one test(s) (CRH, desmopressin, or HDDST) and diagnostic reference standard(s) (histopathology, petrosal sinus sampling, surgical remission, imaging, and long-term follow-up) to establish a CD or EAS diagnosis.
Results
Sixty-two studies were included: 43 reported use of HDDST, 32 CRH test, and 21 desmopressin test. After analysis a CRH test was found to have the highest sensitivity in detecting CD (ACTH 86.9%, 95% confidence interval [CI] 82.1-90.6, cortisol 86.2%, 95%CI 78.3-91.5) and the highest specificity in detecting EAS (ACTH 93.9%, 95%CI 87-98.3, cortisol 89.4%, 95%CI 82.8-93.7). This resulted in a high diagnostic odds ratio (58, 95%CI 43.25-77.47), large area under the curve, and a receiver-operating characteristic (ROC) of 0.934. The diagnostic accuracy of HDDST and desmopressin test(s) was lower than that of the CRH test.
Conclusion
The meta-analysis indicates that a patient with a positive ACTH response after a CRH test is highly likely to have CD. Further studies analysing role of dynamic testing in addition to imaging are needed.

研究目的：目前用于库欣病（CD）与异位促肾上腺皮质激素（ACTH）分泌（EAS）鉴别诊断的检测方法诊断准确性难以解读。本研究旨在识别和评估皮质醇释放激素（CRH）测试、去氨加压素测试及高剂量地塞米松抑制试验（HDDST）在确立CD或EAS诊断中的诊断准确性。
研究设计：本研究为文献系统回顾和荟萃分析。
研究方法：对1990年至2021年间发表的文献进行了MEDLINE、OVID和Web of Science数据库的检索。纳入的文章至少描述了一种测试（CRH、去氨加压素或HDDST）及一种诊断参考标准（组织病理学、蝶窦静脉窦采样、手术缓解、影像学检查和长期随访）以确立CD或EAS的诊断。
研究结果：共纳入62项研究：43项报道了HDDST的使用，32项报道了CRH测试，21项报道了去氨加压素测试。分析结果显示，CRH测试在检测CD（ACTH 86.9%，95%置信区间[CI] 82.1-90.6，皮质醇 86.2%，95%CI 78.3-91.5）中具有最高的敏感性，以及在检测EAS（ACTH 93.9%，95%CI 87-98.3，皮质醇 89.4%，95%CI 82.8-93.7）中具有最高的特异性。这导致诊断优势比（58，95%CI 43.25-77.47）极高，曲线下面积大，以及接受者操作特征（ROC）值为0.934。HDDST和去氨加压素测试的诊断准确性低于CRH测试。
研究结论：荟萃分析表明，CRH测试后ACTH反应阳性的患者极有可能患有CD。需要进一步研究分析动态测试在影像学检查之外的作用。