On the usefulness of levothyroxine suppressive therapy in the medical treatment of benign solitary, solid or predominantly solid, thyroid nodules

Abstract

The efficacy of levothyroxine suppressive therapy in the treatment of benign solitary thyroid nodules is controversial. In order to investigate this issue further we studied 122 patients with a solitary, solid or predominantly solid, thyroid nodule. The benign (colloid) nature of all nodules was proved by fine-needle aspiration biopsy. At the pertechnetate-99m thyroid scanning 91% of the nodules were "cold" and 9% "warm". All the patients received suppressive oral doses of levothyroxine (0.1 to 0.2 mg/day). Fifty-three patients were treated with levothyroxine for 6 months, 31 for 9 months and 38 for 12 months. The size of each nodule before and after treatment was evaluated by high-resolution ultrasonography. The actual suppression of TSH secretion was monitored at 3-month intervals using an ultrasensitive immunometric assay. At the end of levothyroxine treatment, patients were classified as responders (decrease in nodule volume \m=ge\50%,68/122 = 55.7%; mean percent change in nodule volume = \m=-\77.1\ m=+-\ 15.7%), partially responders (decrease in nodule volume <50%, 24/122 = 19.7%; mean percent change in nodule volume = \m=-\27.5\m=+-\10.1%),and nonresponders, when either no change in nodule volume (16/122 = 13.1%) or an increase in nodule volume (14/122 = 11.5%) was observed. In each group serum free T4 rose significantly in response to levothyroxine therapy, whereas serum free T3 remained unchanged. TSH levels were undetectable in all patients. Both the proportion of responders, partially responders and nonresponders, and the mean percent decrease in nodule volume in the responder group were not significantly different in patients treated with levothyroxine for 6, 9 or 12 months, respectively. Therefore, it appears that levothyroxine therapy is effective within 6 months in reducing the size of colloid solitary, solid or predominantly solid, thyroid nodules or in preventing their further growth in about 90% of our patients.Although thyroid suppression is recommended for the medical treatment of benign thyroid nodules (1-3), its efficacy in reducing nodule volume is con¬ troversial. Response rates as high as 61% (4) and as low as 9% (5) have in fact been reported. More recently, Gharib et al. (6) showed that levothyro¬ xine (L-T4) therapy given over a 6-month period did not reduce the size of colloid thyroid nodules despite effective suppression of TSH secretion.In order further to investigate the usefulness of thyroid hormone suppression in the treatment of nodular goitre, we studied the effects on nodule volume of suppressive doses of L-T4 in 122 patients with a colloid solitary, solid or predominantly solid, thyroid nodule. Patients and MethodsThe investigation, which started in November 1988, was conducted in accordance with the principles of the Hel¬ sinki II Declaration. Since the aim of the present study was to investigate the effects of L-T4 therapy on benign (colloid) solitary, solid or predominantly solid (with small cystic spaces =£0.5 cm) thyroid nodules, exclusion criteria included the following:...

Role of cytological characteristics of benign thyroid nodules on effectiveness of their treatment with levothyroxine

“…Cystic nodules are known to be resistant to LT4 therapy [36, 38], but we think this subject is also controversial. It is believed that patients with exclusively or predominantly solid nodules may be more responsive to this therapy than those with a major cystic component, because thyroid cysts have been shown to recur after aspiration despite treatment with LT4 suppression, especially as regards big cystic nodules [9, 39]. According to a previous study [40], only 4% of cystic thyroid lesions were pure cystic nodules, 82% were combined with degenerating benign adenomas or colloid nodules, and 14% were malignant.…”

“…But there are controversial reports about the effectiveness of thyroid hormone suppressive therapy in reducing the volume of benign thyroid nodules [5–8]. Some authors suggest that LT4 therapy is effective in reducing the thyroid nodules [9–12] as well as in preventing the further development of additional nodules [13–15], but some others conclude that LT4 therapy is not effective in reducing the nodule size and in general this attitude was abandoned, except for small colloid nodules in iodine deficient areas [16–19]. Recently this discussion started again with some small clinical studies suggesting that LT4 treatment decreases nodule size [19–21].…”

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).…”

Medical therapy of thyroid autonomy

“…The reports on the clinical outcome of medical therapy of thyroid nodules are very variable as mentioned above (Franke-Raue et al, 1993). Some authors find no significant response compared to placebo, whereas other report a 50 % shrinkage in up to 50 % of the cases (Celani et al, 1990). Most studies, however, are small in number, the drop-out rate is high, there is a predominance of younger patients or there is no placebo group.…”