Background: Management of patients with differentiated thyroid carcinoma with negative diagnostic radioiodide scanning and increased serum thyroglobulin (Tg) concentrations is a widely debated problem. High-dose iodine-131 treatment of patients who have a negative 131 I diagnostic wholebody scan (WBS) is advocated. However, the therapeutic benefit of this 'blind' treatment is not clear. Objective: To investigate the course of serum Tg during thyroid hormone suppression therapy (Tg-on) and clinical outcome in patients with negative diagnostic 131 I scanning and increased serum Tg concentrations during thyroid hormone withdrawal (Tg-off), after treatment with high-dose 131 I. Design: Retrospective single-center study. Methods: Fifty-six patients were treated with a blind therapeutic dose of 150 mCi 131 I. Median followup from this treatment until the end of observation was 4.2 years (range 0.5 -13.5 years). Results: The post-treatment WBS revealed 131 I uptake in 28 patients, but none in the remaining 28 patients. In this study the Tg-on values did not change after treatment in either the positive or the negative post-treatment WBS group. During follow-up, 18 of the 28 patients with a positive posttreatment WBS achieved complete remission, compared with 10 of the 28 patients with a negative post-treatment WBS. Nine patients in the negative group died, but no patients died in the positive post-treatment group (P ¼ 0.001). Conclusions: High-dose iodine treatment in diagnostically negative patients who have a negative posttreatment scan seems to confer no additional value for tumor reduction and survival. In patients with a positive post-treatment scan, high-dose iodine treatment can be used as a diagnostic tool to identify tumor location, and a therapeutic effect may be present in individual cases.

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