Meta-Analysis on the Prevalence and Significance of Incidental Findings in the Thyroid Gland Using Other PET Radiopharmaceuticals Beyond [18F]FDG

Background: Meta-analyses on the prevalence and significance of thyroid incidentalomas at PET (TIP) are available only about [18F]FDG. Focal TIP at [18F]FDG PET is not rare and may be malignant lesions in about one-third of cases. The aim of this study is to perform a meta-analysis on the prevalence and clinical significance of TIP using other PET radiotracers beyond [18F]FDG. Methods: A comprehensive literature search of studies about TIP was carried out using four different databases, screened until 31 December 2024. Only original articles about TIP using radiopharmaceuticals other than [18F]FDG were selected. A proportion meta-analysis on the prevalence and clinical significance of TIP was carried out on a patient-based analysis using a random-effects model. Results: 21 studies (29,409 patients) were included in the meta-analysis. PET was performed using radiolabeled somatostatin analogues (SSA) [n = 5], choline [n = 6], prostate-specific membrane antigen (PSMA) [n = 7], or fibroblast activation protein inhibitors (FAPI) [n = 3]. The uptake pattern of TIP was described as focal, diffuse, or mixed/heterogeneous. The pooled prevalence of TIP was 5.6% for SSA-PET, 6.1% for choline-PET, 4.2% for PSMA-PET, and 3.6% for FAPI-PET. The final diagnosis of TIP with a diffuse pattern was a benign condition or represented a physiological uptake. Conversely, TIP with focal or mixed/heterogeneous pattern may represent a benign condition in most cases, but even a malignant lesion in 6–10% of cases. Conclusions: As for [18F]FDG, TIP using other radiopharmaceuticals is not rare. Most of them are benign, but those with focal or heterogeneous uptake patterns may represent a malignant lesion in some cases (even if the risk of malignancy is lower compared to [18F]FDG PET), thus requiring further evaluation. Further studies are warranted to better clarify the clinical impact of TIP detection.