Indeterminate thyroid nodules (ITN) are commonly encountered among the general population, with a malignancy rate of 10 to 40%. However, many patients may be overtreated with futile surgery for benign ITN. To avoid unnecessary surgery, PET/CT scan is a possible alternative to help differentiate between benign and malignant ITN. In this narrative review, the major results and limitations of the most recent studies on PET/CT efficacy (from PET/CT visual assessment to quantitative PET parameters and recent radiomic features analysis) and on cost-effectiveness (compared to other alternatives (such as surgery)) are presented. PET/CT can reduce futile surgery with visual assessment (around 40%; if ITN ≥ 10 mm). Moreover, PET/CT conventional parameters and radiomic features extracted from PET/CT imaging can be associated together in a predictive model to rule out malignancy in ITN, with a high NPV (96%) when certain criteria are met. Even though promising results were obtained in these recent PET/CT studies, further studies are needed to enable PET/CT to become the definitive diagnostic tool once a thyroid nodule is identified as indeterminate.
