3,5,3'-Triiodothyronine thyrotoxicosis due to increased conversion of administered levothyroxine in patients with massive metastatic follicular thyroid carcinoma.

Abstract

Some patients with massive metastatic thyroid carcinoma exhibit T(3) thyrotoxicosis. We investigated the prevalence and cause of T(3) thyrotoxicosis and the clues to the diagnosis. Serum free T(3) (FT(3)), free T(4) (FT(4)), 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. The serum FT(3) level and FT(3)/FT(4) 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 T(3) thyrotoxicosis or a FT(3)/FT(4) ratio greater than 3.5. One week after withdrawal of levothyroxine, both FT(3) and FT(4) levels decreased. Retrospective measurements of FT(3) in frozen stored sera demonstrated that FT(3) exceeded the upper normal limit when FT(4) began to decrease but remained within the normal range. Tumor tissues showed high D1 and D2 activities. Twenty percent of patients with massive metastatic FC exhibited T(3) thyrotoxicosis, most likely due to increased conversion of T(4) to T(3) by tumor expressing high D1 and D2 activities. Occasional measurement of serum FT(3) in addition to FT(4) and TSH is recommended in patients with massive metastatic FC, especially when serum FT(4) decreases on fixed doses of levothyroxine.