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This version published online on March 11, 2008
Journal of Clinical Endocrinology & Metabolism, doi:10.1210/jc.2008-0139
A more recent version of this article appeared on May 1, 2008
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Submitted on January 22, 2008
Accepted on March 3, 2008

Accuracy of Diagnostic Tests for Cushing's Syndrome. A Systematic Review and Meta-analyses

Mohamed B. Elamin MBBS, M. Hassan Murad MD, MPH, Rebecca Mullan MSc, Dana Erickson MD, Katherine Harris MD, Sarah Nadeem MD, Robert Ennis MD, Patricia J. Erwin MLS, and Victor M. Montori MD, MSc*

Knowledge and Encounter Research Unit, Mayo Clinic, Rochester, MN; Division of Preventive Medicine, Mayo Clinic, Rochester, MN; Division of Endocrinology, Diabetes, Metabolism, Nutrition, Mayo Clinic, Rochester, MN; Department of Medicine, Mayo Clinic, Rochester, MN; Mayo Clinic Libraries, Mayo Clinic, Rochester, MN

* To whom correspondence should be addressed. 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: To summarize evidence on the accuracy of common tests for diagnosing CS.

Data Sources: We searched electronic databases (MEDLINE, EMBASE, Web of Science, Scopus, 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 (DST), and midnight cortisol (MC) 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 MC (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.
Key words: systematic reviews • meta-analysis • Cushing's syndrome • diagnostic tests






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