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Suppressive Therapy with Levothyroxine for Solitary Thyroid Nodules: A Double-blind Controlled Clinical Study and Cumulative Meta-analyses¹

Endocrine Division, Hospital de Clínicas de Porto Alegre, Rua Ramiro Barcellos 2350/2030, 90035–003 - Porto Alegre, RS, Brazil

Address all correspondence and requests for reprints to: Flávio Zelmanovitz, Endocrine Division, Hospital de Clínicas de Porto Alegre, Rua Ramiro Barcellos 2350/2030, Porto Alegre - 90035–003 - RS, Brazil.

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 µg/kg, TSH < 0.3 µIU/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%.

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