Overexpression of Type 2 Iodothyronine Deiodinase in Follicular Carcinoma as a Cause of Low Circulating Free Thyroxine Levels

Thyroid function is normally undisturbed in patients with thyroid carcinoma. We have identified three patients with large or widely metastatic follicular thyroid carcinoma who had a persistently increased ratio of serum T3 to T4 in the absence of autonomous production of T3 by the tumor. To investigate the possibility of tumor-mediated T4 to T3 conversion, we assayed types 1 and 2 iodothyronine selenodeiodinase (D1 and D2) activity in a 965-g follicular thyroid carcinoma resected from one of these patients. The Vmax for D2 was 8-fold higher than in normal human thyroid tissue. Resection of this tumor, leaving the left thyroid lobe intact, normalized the serum T3 to T4 ratio. In two other patients, treatment with sufficient levothyroxine to suppress TSH was associated with a high normal T3 and a subnormal free T4 index. In one, concomitant administration of the D1 inhibitors, propylthiouracil and propranolol, did not decrease the elevated serum T3 to T4 ratio. These data illustrate that increased T4 to T3 conversion in follicular thyroid carcinomas, probably by D2, can cause a significant perturbation in peripheral thyroid hormone concentrations.