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In a study of 136 differentiated thyroid cancer patients referred for radioiodine therapy since January 1991, it was observed that 80 patients had metastatic disease. Of them, 51 had elevated levels of thyroglobulin (Tg), and of these 51 there were 15 patients who had functioning metastases with evidence of thyroid hormone synthesis by these metastases. All but 1 of these 15 cases with normal hormone levels in the circulation were follicular carcinomas with skeletal metastases. The response of these patients to radioiodine was poor. The group of patients with high Tg levels but low hormone synthesis and low circulating hormones responded better to radioiodine. Patients with low Tg levels and low hormone synthesis showed good response to radioiodine—especially patients with residual thyroid tissue after surgery and those with nodal disease.