ABSTRACT: Objectives:This study aims to define a radiomic signature for pre-operative differentiation between subclinical pheochromocytoma (sPHEO) and lipid-poor adrenal adenoma (LPA) in adrenal incidentaloma. The goal was to apply a predictive, preventive, and personalized medical approach to the management of adrenal tumors. Patients and methods:This retrospective study consisted of 265 consecutive patients (training cohort, 212 (LPA, 145; sPHEO, 67); validation cohort, 53 (LPA, 36; sPHEO, 17)). Computed tomography (CT) imaging features were evaluated, including long diameter (LD), short diameter (SD), pre-enhanced CT value (CTpre), enhanced CT value (CTpost), shape, homogeneity, necrosis or cystic degeneration (N/C). Radiomic features were extracted and then were used to construct a radiomic signature (Rad-score) and radiomic nomogram. The area under the receiver operating characteristic curve (AUC) was used to evaluate their performance. Results:Sixteen of three hundred forty candidate features were used to build a radiomic signature. The signature was significantly different between the sPHEO and LPA groups (AUC: training, 0.907; validation, 0.902). The radiomic nomogram based on enhanced CT features (M1) consisted of Rad-score, LD, SD, CTpre, shape, homogeneity and N/C (AUC: training, 0.957; validation, 0.967). The pre-enhanced CT features based radiomic nomogram (M2) included Rad-score, LD, SD, CTpre, shape, and homogeneity (AUC: training, 0.955; validation, 0.958). Conclusions:Our radiomic nomograms based on pre-enhanced and enhanced CT images distinguished sPHEO from LPA. In addition, the promising result using pre-enhanced CT images for predictive diagnostics is important because patients could avoid the additional radiation and risk associated with enhanced CT.