Diagnostic Performance of Common Biochemical Screening Tests for Mild Autonomous Cortisol Secretion in Adrenal Incidentalomas: A Systematic Review and Hierarchical SROC Meta-analysis
In brief
Serum dexamethasone testing detected 98% of study-defined mild cortisol cases
Across 12 studies and 1,420 patients, serum dexamethasone suppression testing had 97.9% sensitivity and 76.8% specificity, suggesting it could help rule out mild autonomous cortisol secretion in adrenal incidentalomas. But all three studies of this test used reference definitions that included dexamethasone suppression, and thresholds varied, so the results do not establish diagnostic superiority; positive findings still need clinical context and possible confirmation.
- Journal
- Endocrine practice : official journal of the American College of Endocrinology and the American Association of Clinical Endocrinologists (Q1)
- Published
- 9 October 2026
- Study design
- Systematic review of cohort studies
- Evidence level
- Level 2, Moderate (CEBM 2a)
- Authors
- Zachary C Bueling, Dani R Douri, August H Berg, Charles E Garrity, Brian M Olson, Bailey R Riehl, et al.
- PMID
- 42855136
- DOI
- 10.1016/j.eprac.2026.09.121
Why clinicians should know about it
- Picked for Biochemistry (medical) (top studies of the week, 11 October 2026): Diagnostic performance of biochemical tests for MACS in adrenal incidentalomas
Abstract
OBJECTIVE: Mild autonomous cortisol secretion (MACS) is a biochemical phenotype in adrenal incidentalomas associated with cardiometabolic risk. Serum and salivary dexamethasone suppression testing (DST), late-night salivary cortisol (LNSC), and urinary free cortisol (UFC) are used, but interpretation is limited by nonuniform disease definitions and reference standards. METHODS: PubMed, Embase, Web of Science, and Scopus were searched through November 19, 2025, in accordance with PRISMA-DTA. QUADAS-2 assessed risk of bias. Bivariate random-effects models generated HSROC estimates and likelihood ratios, and Fagan analyses modeled post-test probabilities. Sensitivity assessments examined reference-standard dependence, diagnostic era, and threshold selection. RESULTS: Twelve studies comprising 1,420 patients were included. Serum DST had sensitivity of 97.9% (95% CI, 88.6-99.6), specificity of 76.8% (64.5-85.7), and a negative likelihood ratio of 0.03 (0.00-0.16). Salivary DST had sensitivity of 74.9% and specificity of 80.5%; LNSC sensitivity was 62.7%, and UFC estimates were highly imprecise. All three serum DST studies used reference definitions that incorporated DST or a related dexamethasone-suppression criterion, leaving no fully independent-reference serum DST pool. Threshold-specific data showed substantial sensitivity-specificity tradeoffs. CONCLUSION: Serum DST produced the lowest pooled negative likelihood ratio against study-defined biochemical reference standards, suggesting potential rule-out value. Incorporation bias, threshold heterogeneity, indirect comparisons, and sparse study counts preclude claims of diagnostic superiority. Positive results require clinical context and confirmatory evaluation when appropriate.
Abstract as published, via PubMed.
For healthcare professionals. The summary is generated by AI from the published abstract, and the evidence level is assigned automatically from the study design on the Oxford CEBM hierarchy. Neither is medical advice. Read the full paper before changing practice.