Accuracy of Laboratory Tests for the Diagnosis of Cushing Syndrome

Abstract Context The diagnosis of Cushing syndrome (CS) can be challenging. It remains to be determined which diagnostic tests are the most accurate. Objective To summarize the accuracy of diagnostic tests for CS using contemporary meta-analytic techniques (hierarchical models). Data Sources PubMed, Embase, Scopus, Web of Science, and the Cochrane Database of Systemic Reviews (inception until August 3, 2018). Study Selection Studies performed in adults that determined the accuracy of one or more diagnostic tests: overnight 1-mg dexamethasone suppression test (DST), 2-day low-dose DST (2d DST), 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 methodological assessments. Data Synthesis One hundred thirty-nine studies (14 140 participants) were included in the analysis. The respective sensitivity, specificity, positive likelihood ratio, and negative likelihood ratio (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 evaluated dex-DDAVP. Meta-regression and a novel network meta-analytic approach suggest that DST is the most sensitive while UFC is the least sensitive. Conclusions All of the included diagnostic tests for CS are highly sensitive and specific. It appears that the DST is the most sensitive while the UFC is less sensitive. The specificity of all first-line tests appears comparable.