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Accuracy of Diagnostic Tests for Cushing’s Syndrome: A Systematic Review and Metaanalyses
Abstract
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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“When the assay upper limit of normal is used as a criterion, the overall evidence supports the diagnostic accuracy of UFC in adults suspected of having Cushing's syndrome (2,51).”
From The diagnosis of Cushing's syndrome: an Endocrine Society Clinical Practice Guideline. (2008) · cites this paper as [2]
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“The four recommended tests have acceptable diagnostic accuracy when the suggested cutoff points are used (2,30).”
From The diagnosis of Cushing's syndrome: an Endocrine Society Clinical Practice Guideline. (2008) · cites this paper as [2]
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“Overall, the evidence in adults suggests that the accuracy of this test is similar to that of UFC (2).”
From The diagnosis of Cushing's syndrome: an Endocrine Society Clinical Practice Guideline. (2008) · cites this paper as [2]
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“Overall, the evidence in adults indicates that in studies with low prevalence of Cushing's syndrome this test has similar performance as the others recommended for initial testing (2).”
From The diagnosis of Cushing's syndrome: an Endocrine Society Clinical Practice Guideline. (2008) · cites this paper as [2]
In the citing paper
“LNSC is emerging as perhaps the most accurate test in diagnosing overt Cushing’s syndrome (240), but for ACS the published studies have given mixed results. In some cases, sensitivity reached 93.8%, but with relatively poor specificity at 79.5% (227) (Table 6).”
From Adrenal incidentaloma (2020) · cites this paper as [240]
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Barbour, L. A., Cobin, R. H., DeGroot, L. J., Glinoer, D., Mandel, S. J., & Edwards, H. A. (2008)
Cirugía adrenal en un hospital de tercer nivel
Santacruz, M. I. S., Gómez, J. A. J., Ruezga, K. L. L., González, L. R. R., Martín, R. A., Cervantes, L. F. C., & Valles, S. G. A. (2013)
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Kaltsas, G., & Chrousos, G. P. (2011) · Endocrine updates · doi:10.1007/978-1-4614-0011-0_5
Yamada, H. (2015) · Springer eBooks · doi:10.1007/978-3-642-27814-3_118-1
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Hall, G., Hunter, J. M., & Cooper, M. S. (2010) · Cambridge University Press eBooks · doi:10.1017/cbo9780511750441.003
Fischer, A. S., Rizk, C. B., & Hsu, S. (2015) · Cambridge University Press eBooks · doi:10.1017/cbo9781139649520.014
Evaluation and Management of Cushing's
Feelders, R. A. (2015) · The Endocrine Society eBooks · doi:10.1210/mtp4.9781936704941.ch33
Saleh, L. (2017) · Praxis · doi:10.1024/1661-8157/a002832
Adrenal Cushing’s Syndrome: Updates on Overt and Mild Hypercortisolism
Escobar, J. S., Ravikumar, A., & Levine, A. C. (2017) · Contemporary Endocrinology · doi:10.1007/978-3-319-62470-9_10
Physiopathology, Diagnosis, and Treatment of Hypercortisolism
Pivonello, R., Iacuaniello, D., Simeoli, C., Martino, M. C. D., & Colao, A. (2017) · Endocrinology · doi:10.1007/978-3-319-38681-2_12-1
Cushing’s Disease: Common Pitfalls in Diagnosis
Fazeli, P. K. (2018) · Springer eBooks · doi:10.1007/978-3-319-90909-7_4
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Sawant, N., Sharma, A., & Shah, N. S. (2019) · Annals of Indian Psychiatry · doi:10.4103/aip.aip_49_18
4 Functional and Nonfunctional Pituitary Adenomas
Chandra, A., & Aghi, M. K. (2019) · Springer eBooks · doi:10.1007/978-3-319-64379-3_4
A Stratified Approach for Cushing’s Syndrome Diagnosis
Chávez-Castillo, M., Rojas, J., Aguirre, M., Villalobos, M., Salazar, J. J., Bello, L., Áñez, R., Olivar, L. C., Calvo, M. C. C., Herazo-Beltrán, Y., et al. (2019) · Global Journal of Health Science · doi:10.5539/gjhs.v11n10p55
Dexamethasone Suppression Test
Dogra, P., & Vijayashankar, N. P. (2019) · StatPearls
Galm, B. P., & Tritos, N. A. (2020) · Springer eBooks · doi:10.1007/978-3-030-38976-5_18
Metadata
- Authors
- Elamin, M. B., Murad, M. H., Mullan, R., Erickson, D., Harris, K., Nadeem, S., Ennis, R., Erwin, P. J., & Montori, V. M.
- Affiliations
- Mayo Clinic (US)
- Department of Medicine (M.H.M., D.E., K.H., R.E., V.M.M.), Mayo Clinic, Rochester, Minnesota 55905
- Venue
- The Journal of Clinical Endocrinology & Metabolism
- Publisher
- The Endocrine Society
- Published
- 2008-05-01
- Volume
- 93
- Issue
- 5
- Pages
- 1553-1562
- ISSN
- 0021-972X (ISSN-L)
- 1945-7197
- OpenAlex
- W2082303249
- Cited by
- 222
- References
- 54
- Citations by year
- 2026: 2 · 2025: 5 · 2024: 6 · 2023: 7 · 2022: 12 · 2021: 6 · 2020: 15 · 2019: 10 · 2018: 10 · 2017: 17 · 2016: 22 · 2015: 12 · 2014: 10 · 2013: 17 · 2012: 13
- FWCI
- 2.68
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- The Journal of Clinical Endocrinology & Metabolism (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Pituitary Gland Disorders and Treatments
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Adrenal Hormones and Disorders
- Health Sciences › Medicine › Surgery › Adrenal and Paraganglionic Tumors
- Keywords
- Cushing's syndrome, diagnostic accuracy, urinary free cortisol, dexamethasone suppression test, hypercortisolism, likelihood ratios, combined diagnostic testing
- MeSH terms
- Cushing Syndrome, Dexamethasone, Humans, Hydrocortisone
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