Thyroxine Suppression Therapy For Benign, Non-Functioning Solitary Thyroid Nodules: A Quality-Effects Meta-Analysis

Abstract

Levothyroxine (LT4) suppressive therapy for solitary thyroid nodules is not popularly advocated presently because its clinical efficacy and safety are currently considered controversial. This metaanalysis aims to address efficacy issues by using rigorous methods to arrive at a pooled estimate. On the basis of the analysis, it is estimated that LT4 therapy is clearly associated with up to a two-fold increase in the chance of nodule reduction. This translates to a number needed to treat (NNT) of 6 or a 50% decrease in the risk of cancer given nodule reduction. Keeping this definition of efficacy in mind and a low incidence of adverse events with low level LT4 suppression, such an intervention might be appropriate in patients selected on the basis of a low risk for adverse effects. The natural history of thyroid nodules suggests that a third of benign nodules will spontaneously grow to more than 15% of its initial size within one year and this increases to almost all (89%) at five years if these nodules are not treated somehow. 1 The majority of growth has been found in those nodules that have a more solid component. Although the pathogenesis of such growth is poorly understood, thyroid-stimulating hormone (TSH) is presumed to be necessary if not sufficient, and therefore suppression of TSH secretion might be expected to result in a decrease in nodule size or at least prevent any further enlargement.Benign solitary nodules detected by physical examination represent two different pathological processes. In many of these patients, the palpated nodule could simply be the dominant nodule of a multinodular goiter while other solitary nodules are probably true solitary adenomas. The latter can be distinguished by ultrasound and nonrandomized, uncontrolled trials have found that patients with solitary nodules had lesser decreases in nodule size in response to thyroxine therapy than patients with nontoxic diffuse or multinodular goiters.2 Of the randomized trials that have been published, the majority demonstrated some degree of efficacy of thyroxine therapy for solitary thyroid nodules. Meta-analyses of these trials was first attempted in 1998 and showed a reduction in thyroid solitary nodule volume in 17% of patients treated with levothyroxine and inhibition of nodule growth in another 10%.3 A second meta-analysis found that nodules decreased by more than 50% in more patients who received thyroxine therapy, but the treatment response did not reach statistical significance (relative risk [RR] 1.9; 95% confidence interval [CI] 0.9 to 3.8).4 Also, there have been concerns about subclinical hyperthyroidism in treated patients who may be at increased risk for atrial

Patient satisfaction of radiofrequency ablation for symptomatic benign solid thyroid nodules: our experience for 2-year follow up

“…The efficacy of levothyroxine is still controversial. Side effects such as reduction of bone density or atrial fibrillation may be caused by long-term use of levothyroxine [22].…”

Treatment efficacy and safety of ultrasound-guided percutaneous bipolar radiofrequency ablation for benign thyroid nodules

“…[3][4][5][6] However, the efficacy of levothyroxine is still controversial, and long-term treatment with medication may cause adverse effects such as reduction of bone density or atrial fibrillation. 3,4,17 Laser ablation and microwave ablation as thermal ablation therapy have been introduced for treatment of benign thyroid nodules in recent years. 5,18-20 Dossing et al 21 reported that the efficacy of laser ablation for predominantly solid thyroid nodules were superior to those nodules acting as controls.…”

Detection of the Single-Session Complete Ablation Rate by Contrast-Enhanced Ultrasound during Ultrasound-Guided Laser Ablation for Benign Thyroid Nodules: A Prospective Study

“…The clinical efficacy and safety of drug treatment is still controversial. Levothyroxine cannot inhibit the growth of all nodules, and it should not be used for elderly patients or postmenopausal women [5]. Although surgical treatment may be effective, there is a high incidence of complications, including airway obstruction, anesthetic accidents, scarring, recurrent laryngeal nerve injury and iatrogenic hypothyroidism [6].…”