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

• Published in: The journal of clinical endocrinology and metabolism 2008-05, Vol.93 (5), p.1553-1562
• Main Authors: Elamin, Mohamed B., Murad, M. Hassan, Mullan, Rebecca, Erickson, Dana, Harris, Katherine, Nadeem, Sarah, Ennis, Robert, Erwin, Patricia J., Montori, Victor M.
• Format: Article
• Language: English
• Subjects: Accuracy; Adrenals. Adrenal axis. Renin-angiotensin system (diseases); Adrenocorticotropic hormone; Biological and medical sciences; Cortisol; Cushing Syndrome - diagnosis; Dexamethasone; Endocrinopathies; Feeding. Feeding behavior; Fundamental and applied biological sciences. Psychology; Hormones; Humans; Hydrocortisone - urine; Medical sciences; Nervous system diseases; Non tumoral diseases. Target tissue resistance. Benign neoplasms; Pituitary; Vertebrates: anatomy and physiology, studies on body, several organs or systems; Vertebrates: endocrinology
• ISSN: 0021-972X; 1945-7197
• DOI: 10.1210/jc.2008-0139

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.