Evaluation of suppressive therapy for cold thyroid nodules with levothyroxine: double-blind placebo-controlled clinical trial

To study the efficacy of levothyroxine suppressive therapy in the management of benign thyroid nodules. We performed a double-blind clinical trial comparing levothyroxine treatment (1.5 to 2.0 mg/kg of body weight daily) (N = 32) with placebo (N = 30) for a 1-year period in patients with a benign, cold thyroid nodule confirmed by biopsy and 99mTc-pertechnetate scanning, who were randomly assigned to the treatment or control group. High-resolution sonography was used to measure the size of the nodules before and after the treatment. Suppression of thyrotropin was evaluated by the administration of thyrotropin-releasing hormone to 10 patients randomly in each group. The mean volume of the thyroid nodules decreased significantly after 6 months in both the levothyroxine group (from 12.8 +/- 11.9 mL to 9.4 +/- 9.8 mL; P = 0.003) and the placebo group (from 13.2 +/- 10.2 mL to 11.5 +/- 8.0 mL; P = 0.003). After 12 months, however, the volume of the nodules had increased. Thus, no significant decrease was found in the mean nodule volume in either study group at 1 year in comparison with the mean volume at baseline (final mean volume: 12.4 +/- 16.7 mL in the levothyroxine group and 11.7 +/- 13.6 mL in the placebo group). Suppressive therapy with levothyroxine for a period of 12 months proved to be ineffective in significantly reducing the size of the thyroid nodules in our patients despite effective suppression of the thyrotropin level.