Simple SummaryWe measured serum thyroglobulin (Tg), a marker of thyroid cancer metastases, in patients operated on with total thyroidectomy for thyroid carcinoma on three different occasions at the beginning of follow-up: 30 days before radioactive iodine therapy (RAI) for remnant ablation (and at least 40 days after thyroidectomy in euthyroidism), at the time of RAI (in hypothyroidism), and 7 days after RAI in euthyroidism. Patients were then followed for at least 3 years searching for possible local recurrences or metastases. Results showed that the first Tg measurement is highly indicative and predictive of the future development of metastases.AbstractIntroduction: Thyroidectomy followed by radioactive iodine therapy (RAI) is the treatment of choice for differentiated thyroid carcinoma (DTC). Serum thyroglobulin (Tg) measurement has proved to be useful for predicting persistent and/or recurrent disease during follow-up of DTC patients. In our study, we evaluated the risk of disease recurrence in patients with papillary thyroid carcinoma (PTC), who were treated with thyroidectomy and RAI, by measuring serum Tg at different time-points: at least 40 days after surgery, in euthyroidism with TSH < 1.5 and usually 30 days before RAI (Tg−30), on the day of RAI (Tg0), and seven days after RAI (Tg+7). Methods: One hundred and twenty-nine patients with PTC were enrolled in this retrospective study. All patients were treated with131I for thyroid remnant ablation. Disease relapse (nodal disease or distant disease) during at least 36 months follow-up was evaluated by serum measurements of Tg, TSH, AbTg at different time points and by imaging techniques (neck ultrasonography,131I-whole body scan (WBS) after Thyrogen®stimulation). Typically, patients were assessed at 3, 6, 12, 18, 24, and 36 months after RAI. We classified patients in five groups: (i) those who developed nodal disease (ND), (ii) those who developed distant disease (DD), (iii) those with biochemical indeterminate response and minimal residual thyroid tissue (R), (iv) those with no evidence of structural or biochemical disease + intermediate ATA risk (NED-I), and (v) those with no evidence of structural or biochemical disease + low ATA risk (NED-L). ROC curves for Tg were generated to find potential discriminating cutoffs of Tg values in all patients’ groups. Results: A total of 15 out of 129 patients (11.63%) developed nodal disease and 5 (3.88%) distant metastases, during the follow-up. We found that Tg−30(with suppressed TSH) has the same sensitivity and specificity than Tg0(with stimulated TSH), and it is slightly better than Tg+7, which can be influenced by the size of the residual thyroid tissue. Conclusion: Serum Tg−30value, measured in euthyroidism 30 days before RAI, is a reliable prognostic factor to predict future nodal or distant disease, thus allowing to plan the most appropriate therapy and follow-up.