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Cited by 222Pituitary Gland Disorders and TreatmentsAdrenal Hormones and DisordersAdrenal and Paraganglionic Tumors

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

Elamin, Mohamed B., Murad, M. Hassan, Mullan, Rebecca, Erickson, Dana, Harris, Katherine, Nadeem, Sarah, Ennis, Robert, Erwin, Patricia J. +1 more·2008·The Journal of Clinical Endocrinology & Metabolism
DOI 10.1210/jc.2008-0139
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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.

    “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]

    The Summary of findings says UFC has substantial evidence supporting its use to detect Cushing’s syndrome, and the pooled results table reports diagnostic accuracy across 14 UFC studies. The Subgroup analyses section identifies an assay-upper-limit cutoff, but the reported UFC estimate is pooled across studies rather than shown specifically for that cutoff. The Conclusions also limit the apparent accuracy to referral practices enriched with patients with Cushing’s syndrome; performance in usual clinical practice remains unclear. Page numbers were not available in our copy. (LLM, conf=0.83)

    Experimental — accuracy not yet measured

  • The four recommended tests have acceptable diagnostic accuracy when the suggested cutoff points are used.

    “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]

    The Conclusions state that commonly used tests appear highly accurate in referral practices with samples enriched for Cushing’s syndrome, but that their performance in usual clinical practice is unclear. The Data extraction section says the review used cutoffs chosen by the primary studies, selecting those with the best performance when several were available; it does not establish accuracy specifically at the suggested cutoff points. (LLM, conf=0.85)

    Experimental — accuracy not yet measured

  • The accuracy of late-night salivary cortisol in adults is similar to that of UFC.

    “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]

  • In adults with low prevalence of Cushing's syndrome, the 1-mg overnight DST has similar performance to other recommended initial tests.

    “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]

  • Late-night salivary cortisol is emerging as perhaps the most accurate test in diagnosing overt Cushing's syndrome, but for autonomous cortisol secretion published studies have given mixed results; in some cases sensitivity reached 93.8% with specificity of 79.5%.

    “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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3 of the 54 references couldn’t be matched to a known paper.

Research works printed but not linked: 1

  1. Montori VM, Guyatt GH 2003 Evidence-based medicine and the diagnostic process. In: Price C, Christenson R, eds. Evidence-based laboratory medicine. Washington, DC: AACC Press; 1-19

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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
ORCID
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
DOI
10.1210/jc.2008-0139
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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