ObjectiveThis study evaluated low-activity I-131 therapy in patients with papillary thyroid carcinoma (PTC) of intermediate risk with higher risk features' who had low nonstimulated thyroglobulin (Tg) after thyroidectomy. Design and PatientsThis was a prospective study including 102 patients with tumours >1 cm and aggressive histology; and/or >3 positive lymph node (LN) or LN >15 cm or exhibiting macroscopic extracapsular extension, and clinically apparent (cN1); and/or a combination of a tumour >4 cm, microscopic extrathyroidal extension and LN metastases (cN1). After thyroidectomy, all patients had nonstimulated Tg < 03 ng/ml and negative antithyroglobulin antibodies (TgAb) and neck ultrasonography (US). The patients were treated with a low activity of I-131 (1110 or 1850 MBq). ResultsPost-therapy whole-body scanning (RxWBS) showed ectopic uptake in four patients. When evaluated 12 months after I-131 therapy, nonstimulated Tg 02 ng/ml with negative TgAb and US, defined as excellent response to initial therapy, was achieved in 101 patients (99%). Only one patient with positive initial RxWBS had structural disease. During follow-up, four patients (4%) relapsed, including LN metastases in two, pulmonary metastases in one, and elevated Tg in one. The other 98 patients remained with nonstimulated Tg 02 ng/ml and negative TgAb and US. There was no case of death due to the tumour. ConclusionsWe conclude that in intermediate-risk patients with higher risk features', low nonstimulated Tg measured with a second-generation assay can be used as criterion for the administration of low I-131 activities (1850 MBq or less).