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Long-Term Changes in Nodular Goiter: A 5-Year Prospective Randomized Trial of Levothyroxine Suppressive Therapy for Benign Cold Thyroid Nodules

Department of Endocrine, Metabolic, and Digestive Diseases, and Diagnostic Imaging Department (R.F., C.M.P.), Ospedale Regina Apostolorum, Albano; Systematic Medical Therapy Institute, Umberto I Polyclinic (V.B.); and the Department of Experimental Medicine, La Sapienza University (F.N.), Rome, Italy

Address all correspondence and requests for reprints to: Dr. Enrico Papini, Department of Endocrine, Metabolic, and Digestive Diseases, Ospedale Regina Apostolorum, Via San Francesco 50, 00041 Albano, Rome, Italy.

We studied for 5 yr a homogeneous group of 83 patients randomly assigned to a levothyroxine (L-T₄) suppressive therapy or to a control group to evaluate changes in nodule or thyroid size, appearance of new nodules, and correlations with clinical parameters.

In the control group, mean nodule volume increased significantly after 5 yr (2.12 ± 1.46 vs. 1.46 ± 0.77 mL), whereas in the treatment group it decreased, although not significantly (1.45 ± 1.17 mL vs. 1.53 ± 0.61 mL). Baseline nodule volume was not different in the two groups, but a significant difference was observed at 5 yr. After 5 yr, sonograms detected 12 new nodules in the control group (28.5%) and 3 (7.5%) in the treatment group. Nodule shrinkage was more frequent in patients with complete TSH suppression, but no correlation was found with other parameters. A significant increase in thyroid size was observed in the control group.

In conclusion, long term TSH suppression induced volume reduction in only a subgroup of thyroid nodules, but effectively prevented the appearance of new lesions and increases in nodule and thyroid volume. As the changes in the natural history of nodular goiter are related to prolonged TSH suppression, which can induce unfavorable side-effects, L-T₄ suppressive therapy should be reserved for small nodules in younger patients.

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