Impact of Size Thresholds on the Diagnosis of Incidental Adrenal Lesions: A Systematic Review and Meta-Analysis

Background: Preferred size-threshold recommendations for management of incidental adrenal lesions remain controversial. Purpose: This meta-analysis aimed to compare the diagnostic accuracy of different size thresholds for detecting malignancy in patients with incidental adrenal lesions on imaging. Materials and Methods: A systematic review of MEDLINE, Embase, Scopus, the Cochrane Library, and the gray literature, covering the period from inception to September 2021, was performed. Studies with >10 patients evaluating the diagnostic accuracy of imaging size thresholds for detecting malignancy in patients with incidental adrenal lesions and no prior history of cancer were included. Study, clinical, imaging, and accuracy data for eligible studies were independently acquired by two reviewers. Primary meta-analysis was performed using a bivariate mixed-effects regression model. Risk of bias was evaluated using the Quality Assessment of Diagnostic Accuracy Studies-2 (QUADAS-2) tool. Results: From 2,690 citations, 40 studies (9,794 patients with mean age ranging from 41 to 66 years) were included. Most (36 of 40) were retrospective single-center studies. CT with or without MRI served as the index test(s). Sensitivity and specificity values, respectively, by size threshold used in the included studies were as follows: 85% (95% confidence interval [CI] 74%-91%) and 39% (95% CI 23%-57%) for 3-cm thresholds; 85% (95% CI 78%-90%) and 75% (95% CI 62%-85%) for 4-cm thresholds; 70% (95% CI 56%-81%) and 74% (95% CI 59%-85%) for 5-cm thresholds; and 75% (95% CI 67%-82%) and 77% (95% CI 62%-87%) for 6-cm thresholds. No cause for variability in sensitivity or specificity was identified on subgroup analysis of the 4-cm threshold. Nearly half of the studies (19 of 40) had at least one QUADAS-2 domain with a high risk of bias. Conclusions: A 4-cm size threshold demonstrates the highest combined sensitivity and specificity, with a preserved specificity compared with higher size thresholds, but with a trend toward improved sensitivity. Future research reevaluating 4-5 cm size thresholds while excluding characteristically benign lesions by imaging may help redefine a size threshold that has improved specificity but preserved sensitivity, compared with the existing 4-cm threshold.