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Background and Objectives The effectiveness of suppressive therapy with Levothyroxine in benign thyroid nodule is controversial. The favorable response varies between 9-68%. The aim of this study was to evaluate the effect of Levothyroxine suppressive therapy on benign thyroid nodules in comparison with untreated patients. Subjects and Method A total 98 patients diagnosed with benign thyroid nodules by high resolution ultrasonography and fine needle aspiration cytology from January 2001 to June 2007 was evaluated retrospectively. The case group included 55 patients who received Levothyroxine suppressive therapy for longer than 6 months with documentation of thyroid stimulating hormone (TSH) suppression level. The control group included 43 patients who were followed up without any treatment. We measured TSH, free T4, and thyroid nodule volume by ultrasound every 6 months. Results In 13 patients (23.6%) of the case group, nodule volume decreased more than 50% after the Levothyroxine suppressive therapy. In 10 (23.2%) of the control group, nodule volume decreased more than 50 % after the follow-up of 6 months. There was no significant difference between the two groups. The change of nodule volume was not related to the TSH suppression level, the number of nodule or the type of nodule. Conclusion We concluded that Levothyroxine suppressive therapy was not effective in volume reduction of benign thyroid nodules.

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