Reduction of thyroid nodule volume by levothyroxine and iodine alone and in combination: A randomized, placebo-controlled trial

Abstract

Context: Nodular goiter is common world wide, but there is still debate over the medical treatment. Objective: The objective of the study was the measurement of the effect of a treatment with (nonsuppressive) T 4, iodine, or a combination of both compared with placebo on volume of thyroid nodules and thyroid. Design: This was a multicenter, randomized, double-blind trial in patients with nodular goiter in Germany [LISA (Levothyroxin und Iodid in der Strumatherapie Als Mono-oder Kombinationstherapie) trial]. Setting: The study was conducted in outpatient clinics in university hospitals and regional hospitals and private practices. Participants: One thousand twenty-four consecutively screened and centrally randomized euthyroid patients aged 18-65 yr with one or more thyroid nodules (minimal diameter 10 mm) participated in the study. Intervention: Intervention included placebo, iodine (I), T 4, or T 4+I for 1 yr. T 4 doses were adapted for a TSH target range of 0.2- 0.8 mU/liter. Outcome Measures: The primary end point was percent volume reduction of all nodules measured by ultrasound, and the main secondary end point was a change in goiter volume. Results: Nodule volume reductions were -17.3% [95% confidence interval (CI) -24.8/-9.0%, P < 0.001] in the T 4+I group,-7.3% (95% CI-15.0/+1.2%, P = 0.201) in the T 4 group, and -4.0% (95% CI - 11.4/+4.2%, P = 0.328) in the I group as compared with placebo. In direct comparison, the T 4+I therapy was significantly superior to T 4 (P = 0.018) or I (P = 0.003). Thyroid volume reductions were -7.9% (95% CI - 11.8/-3.9%, P < 0.001), -5.2% (95% CI - 8.7/-1.6%, P = 0.024) and -2.5% (95% CI - 6.2/+1.4%, P = 0.207), respectively. The T 4+I therapy was significantly superior to I (P = 0.034) but not to T 4 (P = 0.190). Conclusion: In a region with a sufficient iodine supply, a 1-yr therapy with a combination of I and T4 with incomplete suppression of thyrotropin reduced thyroid nodule volume further than either component alone or placebo. Copyright © 2011 by The Endocrine Society.