Thyroxine suppressive therapy of benign solitary thyroid nodules: a prospective randomized study

Patients with solitary thyroid nodules that are benign on aspiration biopsy are often treated nonsurgically. To find out if thyroxine therapy is effective, 74 patients were randomized to receive levothyroxine treatment or nothing. There were 8 males and 66 females. Their mean age was 39 years. The mean nodule size was 3.6 cm and the mean nodule duration was 11 months. All patients had normal serum thyroxine and thyroid stimulating hormone (TSH) levels, and positive thyrotropin releasing hormone (TRH) tests. The dose of thyroxine was adjusted until the TRH test was negative. Patients were followed at 6-month intervals in the first 2 years and yearly thereafter, with measurement of the nodule diameter. The mean follow-up period was 1.5 years. In the 37 patients receiving thyroxine therapy, 8 had disappearance of nodules, 6 had greater than 50% reduction in nodule size. In 19, the nodules were unchanged and in 4, the nodules were enlarged. In the 37 patients receiving no drug, 8 had disappearance of nodules, 5 had greater than a 50% reduction in nodule size, 17 had nodules unchanged, and 7 had enlarged nodules (p greater than 0.9). The mean reduction in nodule diameter at various follow-up periods was greater in the thyroxine group, but the difference did not reach statistical significance. Carcinoma was found in 1 patient in each group and both of them experienced nodule enlargement. We conclude that an adequate suppressive dose of levothyroxine does not alter the natural course of benign solitary thyroid nodules. An enlargement of the nodule or a change in its consistency should be further investigated to exclude malignancy.