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

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Abstract

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.

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