Accuracy of laboratory tests for the diagnosis of cushing syndrome

Abstract

Context: The diagnosis of Cushing syndrome (CS) can be challenging. It remains to bedetermined which diagnostic tests are the most accurate.Objective: To summarize the accuracy of diagnostic tests for CS using contemporary metaanalytic techniques (hierarchical models).Data Sources: PubMed, Embase, Scopus, Web of Science, and the Cochrane Database ofSystemic Reviews (inception until August 3, 2018).Study Selection: Studies performed in adults that determined the accuracy of one or morediagnostic tests: overnight 1-mg dexamethasone suppression test (DST), 2-day low-dose DST (2dDST), 24-hour urinary free cortisol (UFC), late-night salivary cortisol (LNSC), midnight serum cortisol(MSC), and the dexamethasone-suppressed CRH (dex-CRH) and desmopressin (dex-DDAVP) tests.Data Extraction: Two authors independently extracted data and performed methodologicalassessments.Data Synthesis: One hundred thirty-nine studies (14 140 participants) were included in theanalysis. The respective sensitivity, specificity, positive likelihood ratio, and negative likelihoodratio (95% confidence interval [CI]) estimates include the following: DST 98.6% (96.9%-99.4%),90.6% (86.4%-93.6%), 10.5 (7.2-15.3), and 0.016 (0.007-0.035); 2d DST 95.3% (91.3%-97.5%),92.8% (85.7%-96.5%), 13.2 (6.47-27.1), and 0.051 (0.027-0.095); UFC 94.0% (91.6%-95.7%),93.0% (89.0%-95.5%), 13.3 (8.47-21.0), and 0.065 (0.046-0.092); LNSC 95.8% (93.%-97.2%),93.4% (90.7%-95.4%), 14.6 (10.3-20.7), and 0.045 (0.030-0.066); MSC 96.1% (93.5%-97.6%),93.2% (88.1%-96.3%), 14.2 (7.96-25.2), and 0.042 (0.026-0.069); and dex-CRH 98.6% (90.4%-99.8%), 85.9% (67.6%-94.7%), 7.0 (2.80-17.6), and 0.016 (0.002-0.118). A single study evaluateddex-DDAVP. Meta-regression and a novel network meta-analytic approach suggest that DST isthe most sensitive while UFC is the least sensitive.Conclusions: All of the included diagnostic tests for CS are highly sensitive and specific. Itappears that the DST is the most sensitive while the UFC is less sensitive. The specificity of allfirst-line tests appears comparable.