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

OBJECTIVE
Diagnostic accuracy of testing currently used for the differential diagnosis of Cushing's disease (CD) vs ectopic -ACTH secretion (EAS) is difficult to interpret. The present study aimed to identify and evaluate the 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 the diagnostic reference standard(s) (histopathology, petrosal sinus sampling, surgical remission, imaging, and long-term follow-up) used to establish a CD or EAS diagnosis.


RESULTS
Sixty-two studies were included: 43 reported the use of HDDST, 32 CRH test, and 21 desmopressin test. 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.