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Accuracy of Diagnostic Tests for Cushing’s Syndrome: A Systematic Review and Metaanalyses

Knowledge and Encounter Research Unit (M.B.E., M.H.M., R.M., P.J.E., V.M.M.), Division of Preventive Medicine (M.H.M.), Division of Endocrinology, Diabetes, Metabolism, Nutrition (D.E., S.N., V.M.M.), Department of Medicine (M.H.M., D.E., K.H., R.E., V.M.M.), Mayo Clinic, and Mayo Clinic Libraries (P.J.E.), Mayo Clinic, Rochester, Minnesota 55905

Address all correspondence and requests for reprints to: Victor M. Montori, M.D., M.Sc., Mayo Clinic, W18A, 200 First Street SW, Rochester, Minnesota 55905. E-mail: montori.victor{at}mayo.edu.

Context: The diagnosis of Cushing’s syndrome (CS) requires the use of tests of unregulated hypercortisolism that have unclear accuracy.

Objective: Our objective was to summarize evidence on the accuracy of common tests for diagnosing CS.

Data Sources: We searched electronic databases (MEDLINE, EMBASE, Web of Science, Scopus, and citation search for key articles) from 1975 through September 2007 and sought additional references from experts.

Study Selection: Eligible studies reported on the accuracy of urinary free cortisol (UFC), dexamethasone suppression test (DST), and midnight cortisol assays vs. reference standard in patients suspected of CS.

Data Extraction: Reviewers working in duplicate and independently extracted study characteristics and quality and data to estimate the likelihood ratio (LR) and the 95% confidence interval (CI) for each result.

Data Synthesis: We found 27 eligible studies, with a high prevalence [794 (9.2%) of 8631 patients had CS] and severity of CS. The tests had similar accuracy: UFC (n = 14 studies; LR+ 10.6, CI 5.5–20.5; LR– 0.16, CI 0.08–0.33), salivary midnight cortisol (n = 4; LR+ 8.8, CI 3.5–21.8; LR– 0.07, CI 0–1.2), and the 1-mg overnight DST (n = 14; LR+ 16.4, CI 9.3–28.8; LR– 0.06, CI 0.03–0.14). Combined testing strategies (e.g. a positive result in both UFC and 1-mg overnight DST) had similar diagnostic accuracy (n = 3; LR+ 15.4, CI 0.7–358; LR– 0.11, CI 0.007–1.57).

Conclusions: Commonly used tests to diagnose CS appear highly accurate in referral practices with samples enriched with patients with CS. Their performance in usual clinical practice remains unclear.

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