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3,5,3'-Triiodothyronine Thyrotoxicosis due to Increased Conversion of Administered Levothyroxine in Patients with Massive Metastatic Follicular Thyroid Carcinoma

Departments of Surgery (A.M., Y.T., Y.I., A.M., K.K., F.M.) and Medicine (N.A.), Kuma Hospital, Kobe 650-0011, Japan; and Department of Medicine (N.T., E.N., M.N.), Kansai Medical University, Osaka 570-8506, Japan

Address all correspondence and requests for reprints to: Akira Miyauchi, M.D., Ph.D., Department of Surgery, Kuma Hospital, 8-2-35 Shimoyamate-dori, Chuo-ku, Kobe 650-0011, Japan. E-mail: miyauchi{at}kuma-h.or.jp.

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 seven patients, respectively). Patients without recurrence served as controls. Thyrotoxic patients were reexamined 1 wk after withdrawal of levothyroxine. Type 1 and type 2 iodothyronine deiodinase (D1 and D2) activities were measured in three 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 increased conversion of T₄ to T₃ 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.