Suppressive therapy with levothyroxine for solitary thyroid nodules: a double-blind controlled clinical study and cumulative meta-analyses

Levothyroxine suppressive treatment of solitary thyroid nodules is controversial. A 1-yr prospective randomized placebo-controlled trial was conducted to evaluate the effect of T4 on nodule volume and bone mineral density, and meta-analyses were performed to examine the quantitative synthesis of data from similar designed controlled trials. Forty-five euthyroid patients (42 females, age range: 19-73 yr) with single, colloid nodules were randomized to T4 (21 patients, 2.7 +/- 0.3 microg/kg, TSH < 0.3 microIU/mL) and placebo. Ultrasonography and densitometry were performed at baseline and repeated after treatment. Mean nodule volume or bone mineral density did not change. Nodule reduction more than 50% was observed in 6 of 21 treated patients and 2 of 24 placebo patients (P = 0.12). This study and another 6 prospective controlled trials (minimum 6 months, ultrasonographic nodule evaluation) were included in cumulative meta-analyses (risk-difference method). Nodule volume decreased more than 50% in a significantly higher percentage of patients in the T4 groups (risk difference, 16.7%; 95% confidence intervals, 5.8-27.6%). Four trials evaluated nodule growth with homogeneous results (Q = 0.42). Nodule volume increased more than 50% in a significantly smaller percentage of patients treated with T4 (risk difference, 9.7%; 95% confidence intervals, 2.0-17.4%). In conclusion, T4 treatment is associated with decreased nodule volume in 17% of patients and may inhibit growth in another 10%.