Aims: This study aimed (a) to determine the clinical and histopathologic factors that are related to FDG avidity in the recurrence/metastases of patients with differentiated thyroid carcinoma (DTC) who present with elevated thyroglobulin (Tg) levels and negative 131I whole-body scans (WBSs), (b) to clarify Tg cutoff levels in this setting, and (c) to evaluate the impact of PET/CT on patient management strategies and hence to critically look into the importance of PET/CT in combination with Tg in clinical decision making.
Methods: A total of 105 patients with DTC with negative 131I WBS and neck ultrasound but elevated Tg, who underwent FDG PET/CT for the suspicion of recurrent/metastatic disease, were included in this analysis. All patients had previously undergone total thyroidectomy and radioiodine ablation/therapy. PET/CT results were correlated with Tg levels and clinical and histopathologic characteristics of the primary tumor compared with the follow-up data.
Results: PET/CT was true-positive in 69 patients (of which 23 had surgically amenable disease), true-negative in 20, false-positive in 6 patients and false-negative in 10 patients. Extrathyroidal spread was an independent risk factor related to FDG-avid recurrence. Tumor size was significantly higher in PET-positive patients than others, 2.25 (1.8) versus 1.5 (1.1) cm, P = 0.02. Significant correlation was observed between PET positivity and high Tg levels (P = 0.0001). Receiver operating characteristic curve analysis demonstrated a Tg cutoff of 1.9 ng/mL under thyroid-stimulating hormone suppression, 38.2 ng/mL with thyroid-stimulating hormone stimulation. Among PET-negative patients, no recurrence was detected in patients with undetectable/suppressible Tg in on-therapy state.
Conclusions: PET positivity correlated with extrathyroidal spread, and elevated Tg in recurrent/metastatic DTC. FDG PET/CT in combination with Tg levels was crucial in defining management strategies in patients with DTC with negative 131I WBS. A negative FDG PET/CT scan predicts a favorable prognosis and lack of recurrence on follow-up in patients with “suppressible Tg” levels in the on-therapy state despite significant elevation of Tg in the off-therapy state.