Reduction of Thyroid Nodule Volume by Levothyroxine and Iodine Alone and in Combination: A Randomized, Placebo-Controlled Trial
What this study found
The combination of iodine plus nonsuppressive levothyroxine produced the clearest benefit and was the only active regimen that significantly reduced total nodular volume. Change in total nodular volume after 12 months was -17.3% [95% CI -24.8 to -9.0], P<0.001 with T4+I, compared with -7.3% [95% CI -15.0 to 1.2], P=0.201 with T4 and -4.0% [95% CI -11.4 to 4.2], P=0.328 with iodine. T4+I was superior to T4 (P=0.018) and iodine (P=0.003). Thyroid volume also decreased with T4+I (-7.9% [95% CI -11.8 to -3.9], P<0.001), with smaller reductions for T4 (-5.2%, P=0.024) and no significant effect…
- Study & population
- Randomized, placebo-controlled, multicenter trial conducted at 60 German study centers in euthyroid adults with nodular goiter and one or more thyroid nodules.
- Intervention
- Iodine arm: potassium iodide 150 g per day; T4 arm: levothyroxine 75 g per day; T4+I arm: levothyroxine 75 g per day plus potassium iodide 150 g per day.
- Key limitation
- The trial followed patients for only 12 months, so longer-term durability and safety are uncertain.
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Open PDFOriginal abstract
Context: Nodular goiter is common worldwide, 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) T4, 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), T4, or T4+I for 1 yr. T4 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 T4+I group, −7.3% (95% CI −15.0/+1.2%, P = 0.201) in the T4 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 T4+I therapy was significantly superior to T4 (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 T4+I therapy was significantly superior to I (P = 0.034) but not to T4 (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.