Radiomic Characterization of Adrenal Incidentalomas on NECT: Retrospective Exploratory Study and Systematic Review

Radiomics may aid the noninvasive characterization of adrenal incidentalomas; however, reproducibility is limited by methodological heterogeneity. In this retrospective, single-center, exploratory study, we tested whether radiomic features from baseline non-enhanced computed tomography (NECT) discriminate benign from malignant/metastatic adrenal lesions and contextualized results with a PRISMA 2020 systematic review (PubMed/Scopus 2017–2025; PROSPERO CRD420251276627). Thirty-three patients (36 lesions: 12 lipid-rich adenomas, 9 lipid-poor adenomas, 6 pheochromocytomas, 7 malignant/metastatic lesions, 2 myelolipomas) were included; myelolipomas were excluded from primary comparisons. Two abdominal radiologists performed consensus 3D segmentation on NECT. Using LIFEx (v7.8.0) and IBSI definitions, 42 features were extracted and z-score standardized. LASSO selected four heterogeneity descriptors: First-order Entropy, gray-level co-occurrence matrix (GLCM) entropy, gray-level size zone matrix (GLSZM) non-uniformity, and neighboring gray tone difference matrix (NGTDM) busyness. Heterogeneity increased from lipid-rich adenomas to pheochromocytomas and malignant/metastatic lesions (Kruskal–Wallis, all p < 0.001. Pairwise separability, measured using the Vargha–Delaney A index (VDA) as a rank-based measure of separability, was highest for lipid-rich adenomas versus malignant/metastatic lesions (0.93), intermediate for lipid-poor adenomas versus pheochromocytomas (0.73), and lowest for lipid-rich versus lipid-poor adenomas (0.64). The review identified 18 eligible CT radiomics studies that consistently reported higher entropy/non-uniformity in pheochromocytomas and malignant lesions than in lipid-rich adenomas. Global heterogeneity metrics on NECT may complement conventional CT criteria in indeterminate lesions; external validation with robust reference standards is needed in larger, multicenter cohorts with harmonization.