Diagnostic Performance of Common Biochemical Screening Tests for Mild Autonomous Cortisol Secretion in Adrenal Incidentalomas: A Systematic Review and Hierarchical SROC Meta-analysis.

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.