Radioiodine

Nodular Goiter

Radioiodine is more effective than thyroxine in decreasing goiter size in patients with nodular goiter

Wesche MFT, Tiel-v Buul MMC, Lips P, Smits NJ, Wiersinga WM. A randomized trial comparing levothyroxine with radioactive iodine in the treatment of sporadic goiter. J Clin Endocrinol Metab 2001;86:998-1005.

Summary
Background Patients with a sporadic nontoxic nodular goiter – called sporadic because the patients live in an area of iodine sufficiency – are often treated with thyroxine (T4) to reduce the size of their goiter, although it is little more effective than a placebo. In contrast, iodine-131 (I-131) has proven effective in reducing goiter size in uncontrolled studies. The purpose of this study was to compare the effects of T4 and I-131 in a relatively homogeneous group of patients with nontoxic nodular goiter living in an are where iodine intake is sufficient.

Methods
Sixty four patients with nontoxic nodular goiter were randomly assigned to treatment with I-131 or daily T4 and followed at regular intervals for 2 years. There were 31 women, of whom approximately half were peri- or post-menopausal, and 2 men in each group. Patients with cardiac disorders or severe obstructive symptoms were excluded, but most patients had some symptoms referable to their goiter. The diagnosis was based on demonstration of one or more nodules by ultrasonography (with biopsies negative for thyroid cancer when appropriate) and on technetium (Tc)-99m scans that revealed heterogeneous uptake. Other baseline characteristics of the I-131 and T4 groups, respectively, were: mean age, 49 and 50 years; multinodular goiter, 30 and 29 patients; and median thyroid volume, 60 mL (range, 17 to 198) and 57 mL (range, 18 to 260). The patients had normal serum T4 and triiodothyronine concentrations; their median serum thyrotropin (TSH) concentrations were 0.6 mU/L (I-131 group) and 0.8 mU/L (T4 group) (normal, 0.4 to 4.0), but 10 patients in the I-131 group and 7 patients in the T4 group had low serum TSH concentrations.

In the I-131 group the goal of treatment was to deliver 4.44 MBq (120 uCi)/mL of thyroid tissue, and the administered doses ranged from 444 to 3330 MBq (12 to 90 mCi); T4 was given to patients who had high serum TSH concentrations during follow-up. In the T4 group the initial dose was 2.5 ug/kg/day, and the dose was adjusted to maintain serum TSH concentrations between 0.01 and 0.1 mU/L or serum free T4 concentrations within the upper limit of the normal range. The primary endpoints of the study were goiter size of 1 and 2 years; a secondary endpoint was lumbar spine and hip mineral density at 1 and 2 years.

Results
In the 29 patients in the I-131 group who completed the study, thyroid volume decreased to 36 mL (range 4 to 130) after 1 year and to 30 mL (range 6 to 165) after 2 years; the mean decreases were 38 percent and 44 percent, respectively. In contrast , in the 28 patients in the T4 group who completed the study the median thyroid volume decreased to 54 mL (range, 18 to 243) after 1 year and it was 60 mL (range, 20 to 287) after 2 years; the mean decreases were 7 percent and 1 percent, respectively. More patients in the I-131 group had improvement in symptoms, and their serum TSH concentrations increased approximately 3-fold. In the T4 group, the mean TSH concentration was 0.02 mU/L after 1 and 2 years, and some patients has symptoms of hyperthyroidism. Lumbar spine density did not change in the I-131 group but decreased in the T4 group, whereas hip density did not change in either group.

Conclusion
In patients with sporadic goiter, I-131 is considerably more effective than T4 in decreasing goiter size and ameliorating goiter-related symptoms, and it does not cause loss of bone.

Commentary by Robert D. Utiger, MD This study provides compelling evidence that I-131 is far more effective than T4 in reducing thyroid size in patients with nontoxic nodular goiter, and it does so without causing subclinical hyperthyroidism. These results confirm those of several uncontrolled studies of I-131 (summarized in ref 1), and indeed should put to rest the notion that T4 has any value in these patients. The inclusion of a few patients with a uninodular goiter was unfortunate, because that is probably a different disorder, but it does not detract appreciably from the overall results.

The mean decrease in thyroid volume in these studies was approximately 50 percent in the first year after treatment, with little additional increase thereafter, but approximately 20 percent of patients had little decrease or even an increase in goiter size. A few patients have radiation thyroditis soon after treatment, some later become hypothyroid, and a few develop Grave’ hyperthyroidism, presumably a result of autoimmunization (1). If compressive symptoms are prominent, then I-131 therapy is no match for thyroidectomy. If they are not, and treatment is indicated to reduce goiter size or ameliorate subclinical hyperthyroidism, then I-131 should be given.

Reference: 1. Samuels MH. Evaluation and treatment of sporadic nontoxic goiter – some answers and more questions. J Clin Endocrinol Metab 2001;86:994-7.

Clinical Thyroidology 2001;Vol XIII, Issue 2:p 2.