Radioiodine treatment of hyperthyroidism

Abstract

Duration of radioprotective effects of antithyroid drug therapy is still not clear

In this week's BMJ, Walter and colleagues¹ present a systematic review and meta-analysis of randomised controlled trials of the effects of antithyroid drugs on treatment with radioiodine. Radioiodine is perceived as a simple and cost effective treatment of hyperthyroidism.² A β adrenergic blocker, such as propranolol (total daily dose of 80-160 mg), can usually provide appreciable relief of symptoms between the initial consultation and administration of radioiodine, and for the next six to eight weeks until treatment is effective.

In elderly patients and in those with severe thyrotoxicosis or cardiovascular complications, such as atrial fibrillation and heart failure, it is common practice to restore euthyroidism first with antithyroid drugs. This prevents the rare, but well recognised, worsening of hyperthyroidism caused by irradiation induced leakage of stored thyroid hormones seen within the first few days,³ an important consideration given the increased mortality in the early weeks after giving radioiodine.⁴

Antithyroid drugs do not prevent an increase in serum thyroid hormone concentrations, but any increase is from a lower baseline and has no clinical relevance.⁵ The other advantage of pretreatment with antithyroid drugs in severe hyperthyroidism, when the concentration of free thyroxine in the serum is usually more than 60 pmol/l (normal 10-25), is that a rational discussion about the treatment options is more likely when the patient is euthyroid and, therefore, less agitated and more able to concentrate. In a survey of members of the American Thyroid Association, 31% of correspondents prescribed antithyroid drugs before and 40% after radioiodine treatment for patients with Graves' disease.⁶ The role of antithyroid drugs after radioiodine is simply to buy time until that treatment is effective.

Considerable experience has been gained in using antithyroid drugs as an adjunct to radioiodine treatment in the past 50 years or so, but controversy remains about whether carbimazole (and its active metabolite, methimazole) and propylthiouracil influence the actions of radioiodine. To some extent this confusion is a reflection of the retrospective nature of many of the studies, most of which are small; patient selection; the type of hyperthyroidism (Graves' disease or toxic nodular goitre) studied; the likelihood that antithyroid drugs were given before and after radioiodine to patients with the most severe disease; the various radioiodine dosage regimens used; and the fact that thyroid status at the time of treatment may alter iodine kinetics and the effectiveness of radioiodine. Many of these difficulties were identified by Walter and colleagues.¹ They found that antithyroid drugs given in the week before or after radioiodine increased the risk of treatment failure (relative risk 1.28, 95% confidence interval 1.07 to 1.52) and reduced the risk of hypothyroidism (0.68, 0.53 to 0.87). Overall the quality of evidence was poor.

Although the study is valuable in that it highlights the inadequacy of data collection over many years, the conclusions are not useful for patient management. Indeed, current beliefs, such as the radioprotective effect of propylthiouracil lasting longer than that of carbimazole,⁷ were not supported by this type of analysis. So what should the clinician do while awaiting better quality trials?

For the hyperthyroid patient, judged sufficiently unwell to justify adjunctive antithyroid treatment for four to six weeks before radioiodine, it may be counterproductive to stop the drug for seven days or more either side of treatment. Evidence exists, however, that the radioprotective effect of antithyroid drugs can be overcome by increasing the dose of radioiodine, perhaps by as little as 25%.⁸ A pragmatic approach, used in our clinic for several years, is to discontinue the antithyroid drug for 48 hours before and after 400 MBq radioiodine—a dose greater than that used in most of the studies under scrutiny. When re-started the antithyroid drug should be given for six weeks and thyroid status should be assessed at eight weeks. Failure to achieve euthyroidism or an appreciable improvement in hyperthyroidism is an indication for further radioiodine.

Although radioiodine is increasingly the treatment of choice in patients with hyperthyroidism due to Graves' disease, we need to be more cautious about a treatment that almost always causes hypothyroidism, especially when we have no consensus on what constitutes correct thyroid hormone replacement.⁹ Some patients abhor the idea of any form of irradiation. In addition, radioiodine, rather than antithyroid drugs or surgery, is most closely associated with a deterioration in ophthalmopathy, a risk that can be reduced by concomitant treatment with steroids.¹⁰ Patients worry that they will gain excessive weight if rendered hypothyroid, and this may be true if serum concentrations of thyroid stimulating hormone are simply restored to the reference range with thyroxine.¹¹

Of some concern are the recent reports that radioiodine treatment itself may cause increased morbidity and mortality from cardiovascular disease.¹² Therefore, it should be remembered that long term treatment with carbimazole for 10 years or more is a viable alternative,¹³ and that subtotal thyroidectomy in experienced hands guarantees patients the longest existence without taking drugs.