Reduction of Thyroid Nodule Volume by Levothyroxine and Iodine Alone and in Combination: A Randomized, Placebo-Controlled Trial

Randomized, placebo-controlled, multicenter trial conducted at 60 German study centers in euthyroid adults with nodular goiter and one or more thyroid nodules. Active intervention arm sizes were iodine n=198, T4 n=206, and T4+I n=191; total randomized was 1020.

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. All regimens were given daily for 12 months; route was not stated.

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 for iodine (-2.5%, P=0.207). Authors concluded that in iodine-sufficient regions, 1 year of combined iodine and nonsuppressive levothyroxine reduces thyroid nodule volume more than either component alone or placebo.

The trial followed patients for only 12 months, so longer-term durability and safety are uncertain. Generalizability is limited to euthyroid Caucasian adults treated in German centers in an iodine-sufficient setting, and the individual iodine and levothyroxine arms did not show statistically significant primary nodule-volume reductions. Active-arm sample sizes were moderate rather than large, which limits precision for subgroup or safety inference.