PNA Medical Corner: Lab Test Accuracy in Cushing’s

This month the PNA Medical Corner focuses on an article co-authored by Dr. Anne Klibanski, a member of the PNA. The study analyzes the accuracy of diagnostic tests for Cushing’s syndrome and finds that the dexamethasone suppression test is more sensitive than the 24-hour urinary free cortisol test.
J Clin Endocrinol Metab. 2020 Mar 5. pii: dgaa105. doi: 10.1210/clinem/dgaa105. [Epub ahead of print]Klibanski
Accuracy of laboratory tests for the diagnosis of Cushing's syndrome.
Galm BP1, Qiao N1,2, Klibanski A1, Biller BMK1, Tritos NA1.
Author information
Abstract 

CONTEXT:

The diagnosis of Cushing's syndrome (CS) can be challenging. It remains to be determined which diagnostic tests are the most accurate.

OBJECTIVE:

To summarize the accuracy of diagnostic tests for CS using contemporary meta-analytic techniques (hierarchical models).

DATA SOURCES:

PubMed, Embase, Scopus, Web of Science, and the Cochrane Database of Systemic Reviews (inception until August 3, 2018).

STUDY SELECTION:

Studies performed in adults that determined the accuracy of one or more diagnostic tests: overnight 1 mg dexamethasone suppression test (DST), two-day low-dose DST (2d DST), 24-hour urinary free cortisol (UFC), late-night salivary cortisol (LNSC), midnight serum cortisol (MSC), and the dexamethasone-suppressed CRH (dex-CRH) and desmopressin (dex-DDAVP) tests.

DATA EXTRACTION:

Two authors independently extracted data and performed methodological assessments.

DATA SYNTHESIS:

One hundred thirty nine studies (14,140 participants) were included in the analysis. The respective sensitivity, specificity, positive likelihood ratio, and negative likelihood ratio (95% CI) estimates are: DST 98.6% (96.9-99.4%), 90.6% (86.4-93.6%), 10.5 (7.2-15.3), and 0.016 (0.007-0.035); 2d DST 95.3% (91.3-97.5%), 92.8% (85.7-96.5%), 13.2 (6.47-27.1), and 0.051 (0.027-0.095); UFC 94.0% (91.6-95.7%), 93.0% (89.0-95.5%), 13.3 (8.47-21.0), and 0.065 (0.046-0.092); LNSC 95.8% (93.8-97.2%), 93.4% (90.7-95.4%), 14.6 (10.3-20.7), and 0.045 (0.030-0.066); MSC 96.1% (93.5-97.6%), 93.2% (88.1-96.3%), 14.2 (7.96-25.2), and 0.042 (0.026-0.069); and dex-CRH 98.6% (90.4-99.8%), 85.9% (67.6-94.7%), 7.0 (2.80-17.6), and 0.016 (0.002-0.118). A single study evaluated dex-DDAVP. Meta-regression and a novel network meta-analytic approach suggest that DST is the most sensitive while UFC is the least sensitive.

CONCLUSIONS:

All of the included diagnostic tests for CS are highly sensitive and specific. It appears that the DST is the most sensitive while the UFC is less sensitive. The specificity of all first-line tests appears comparable.
© Endocrine Society 2020. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

KEYWORDS:

Cushing’s syndrome; Dexamethasone suppressed CRH test; Dexamethasone suppression test; Late night salivary cortisol; Midnight serum cortisol; Urinary free cortisol or urine free cortisol
PMID: 32133504 DOI:10.1210/clinem/dgaa105

Accuracy of laboratory tests for the diagnosis of Cushing's syndrome.
Galm BP, Qiao N, Klibanski A, Biller BMK, Tritos NA.
J Clin Endocrinol Metab. 2020 Mar 5. pii: dgaa105. doi: 10.1210/clinem/dgaa105. [Epub ahead of print]
Front Endocrinol (Lausanne). 2020 Feb 18;11:16. doi: 10.3389/fendo.2020.00016. eCollection 2020.

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