Objective: Some patients with massive metastatic thyroid carcinoma exhibit T₃ thyrotoxicosis. We investigated the prevalence and cause of T₃ thyrotoxicosis and the clues to the diagnosis.

Design: Serum free T₃ (FT₃), free T4 (FT₄) and TSH were measured in patients with massive metastases from papillary, follicular, or medullary thyroid carcinomas (31, 20, and 7 patients, respectively). Patients without recurrence served as controls. Thyrotoxic patients were reexamined one week after withdrawal of levothyroxine. Type 1 (D1) and type 2 (D2) iodothyronine deiodinase activities were measured in 3 tumor tissues from thyrotoxic patients.

Main Outcome: The serum FT₃ level and FT₃/FT₄ ratio in the follicular carcinoma (FC) group were significantly higher than those in the papillary carcinoma group or patients without recurrence. Four patients (20%) in the FC group but none in the other groups demonstrated T₃ thyrotoxicosis or a FT₃/FT₄ ratio greater than 3.5. One week after withdrawal of levothyroxine, both FT₃ and FT₄ levels decreased. Retrospective measurements of FT₃ in frozen stored sera demonstrated that FT₃ exceeded the upper normal limit when FT₄ began to decrease but remained within the normal range. Tumor tissues showed high D1 and D2 activities.

Conclusions: Twenty percent of patients with massive metastatic FC exhibited T₃ thyrotoxicosis, most likely due to T₄ to T₃ increased conversion by tumor expressing high D1 and D2 activities. Occasional measurement of serum FT₃ in addition to FT₄ and TSH is recommended in patients with massive metastatic FC, especially when serum FT₄ decreases on fixed doses of levothyroxine.