Effects of Thyroid-Stimulating Hormone Suppression with Levothyroxine in Reducing the Volume of Solitary Thyroid Nodules and Improving Extranodular Nonpalpable Changes: A Randomized, Double-Blind, Placebo-Controlled Trial by the French Thyroid Research Group

Abstract

The efficacy of suppressing TSH secretion with levothyroxine (L-T(4)) in reducing solitary thyroid nodule growth is still controversial. In this prospective multicenter, randomized, double-blind, placebo-controlled trial, 123 patients with a single palpable benign nodule were included and randomly allocated to an 18-month treatment with L-T(4) or placebo. Individual dose was adjusted to allow a serum TSH level below 0.3 mIU/liter. Clinical and ultrasonographic nodule characteristics were assessed before treatment and 3, 6, 12, and 18 months thereafter. The largest mean nodule size assessed on palpation and largest volume, assessed by ultrasonography, decreased in the L-T(4) group and increased slightly in the placebo group [size, -3.5 +/- 7 mm vs. +0.5 +/- 6 mm (P = 0.006); volume, -0.36 +/- 1.71 ml vs. +0.62 +/- 3.67 ml (P = 0.01), respectively]. The proportion of clinically relevant volume reduction (> or =50%) rose significantly in the L-T(4) group [26.6% vs. 16.9% (P = 0.04)]. The proportion of patients with a reduced number of infraclinical additional nodules was significantly higher in the L-T(4) group [9.4% vs. 0 (P = 0.04)]. It is concluded from this study that suppressive L-T(4) therapy is effective in reducing solitary thyroid nodule volume and improving infraclinical extranodular changes.

Management Guidelines for Children with Thyroid Nodules and Differentiated Thyroid Cancer

“…LT 4 therapy has been prescribed to reduce the size of benign thyroid nodules, but the clinical benefit of a small to modest reduction in size is not clear (142)(143)(144)(145)(146)(147). About a third (30.6%) of euthyroid children had a ‡ 50% reduction in nodule size, which was directly correlated with TSH levels (r = 0.640, p < 0.001) and inversely with LT 4 dose (r = -0.389, p = 0.009) (140).…”

Thyroid nodules - Stepwise diagnosis and management

“…167 Some studies have reported that L-thyroxine suppressive therapy results in reduction in nodule volume, especially in small ones, [168][169][170][171] whereas others do not support this finding and suggest that patients with cytologically benign nodules are best followed without thyroxine treatment. 165,172 Moreover, in a 10-year retrospective analysis, 13% of histologically (after surgery) proved PTCs had previously shown a decrease in size during suppressive L-thyroxine therapy.…”

A solid thyroid benign nodule that showed a significant decrease in size and ultrasonographic findings mimicking papillary carcinoma during 16-year follow-up

“…Kuma et al demonstrated that 23% of single nodule enlarged, but 30% disappeared and the remaining showed no change in size on long-term follow-up for 9-11 years based on palpation [5]. Thereafter, several studies that evaluated tumor size on ultrasonography have been published, showing that 4-22% of nodules showed 50% increase and 0-20% showed 50% decrease in volume [6][7][8][9][10][11][12][13]. However, average follow-up periods were less than 5 years in these stud- ings suggestive of papillary carcinoma with negative cytology, we should consider the possibility of a benign nodule degenerating over time.…”