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

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.

Thyroid Volume and Its Relation to Anthropometric Measures in a Healthy Cuban Population

“…Knowledge about thyroid volume is needed for the evaluation of a number of physiological and pathological factors such as iodine deficiency goiter, thyroiditis, multinodular goiter and thyroid cancer, as well as for evaluating the efficacy of levothyroxine therapy [9] and for identifying indications of minimally invasive surgery. Ultrasonography with a linear probe is a useful, practical, safe and comparatively cheap method for assessing thyroid volume [10].…”

Non-surgical approach to the benign nodular goiter: new opportunities by recombinant human TSH-stimulated 131I-therapy

“…The effect of LT4 suppressive therapy on the solitary thyroid nodule volume has been evaluated in several studies [24,25], mostly showing a limited efficacy and only in a fraction of patients. In a recent large, double-blind, randomized trial [26] in patients with either one or more thyroid nodules, a combination of iodine and LT4, aiming at a serum TSH in the range of 0.2-0.8 mU/ l, reduced the thyroid nodule volume by 17.3% after 1 year, which was more than either component alone or placebo. The thyroid volume reduction was merely 7.9%, and was even less if the treatment included either LT4 or iodine alone [26].…”

“…In a recent large, double-blind, randomized trial [26] in patients with either one or more thyroid nodules, a combination of iodine and LT4, aiming at a serum TSH in the range of 0.2-0.8 mU/ l, reduced the thyroid nodule volume by 17.3% after 1 year, which was more than either component alone or placebo. The thyroid volume reduction was merely 7.9%, and was even less if the treatment included either LT4 or iodine alone [26]. Besides the very modest effect (if any) of iodine supplementation, a major hindrance for the use of this treatment is the induction of thyrotoxicosis commonly seen by a sudden increase of iodine intake [27,28].…”

Nuklearmedizinische und radiologische Diagnostik und Therapie der Schilddrüsenerkrankungen

“…Allerdings liegen zum jetzigen Zeitpunkt noch keine Langzeiterfah rungen von mehr als einem Jahr vor [7]. Mittels ausreichender Prophylaxe (z.…”