Has the Use of Antithyroid Drugs for Graves' Disease Become Obsolete?

Abstract

In spite of an experience of almost 50 years of use of antithyroid drugs and radioiodine for the treatment of Graves' disease, the rationale for choice is often obscure. Early reports of high remission rates during thiourea therapy were followed by less optimistic ones, which along with other factors may have fueled the current major shift toward use of radioiodine. This review examines whether or not the use of antithyroid drugs indeed may have become obsolete. The intrathyroidal and extrathyroidal mechanisms of action of the drugs are reviewed with emphasis on their potential immunosuppressive effects. The latter may involve a direct effect on thyroid follicular cells, a direct suppression of TSH receptor antibody formation, or indirect effects mediated via heat shock proteins, oxygen free radicals, and the immune system. Potential factors associated with success or failure with antithyroid drug therapy are discussed, such as the effects of dose and duration of treatment, iodine milieu, and concomitant L-thyroxine therapy. The risks inherent to radioiodine therapy are only briefly described with emphasis on the possible aggravation by radioiodine of preexistent ophthalmopathy. The reader must decide whether the evidence marshalled convincingly indicates that the use of the thiourea compounds should be abandoned. The author thinks not, and is optimistic that imminent discovery of the yet elusive and enigmatic pathogenesis of Graves' disease will permit new and innovative treatment or more effective use of currently available therapies.

Radioiodine treatment of Graves' hyperthyroidism with and without anti-thyroid medication pretreatment in an Australian teaching hospital

“…The relatively high prevalence of hypothyroidism following 131 I therapy (65-70%) in our patients, in comparison with figures from the published literature (up to 30-40% at 2 years and 5% per year thereafter) [3,4], is an unexpected finding because the average doses of 131 I used in both groups were within the recognized range of 5-15 millicuries used in GH [1]; possible explanations for this include the larger glands encountered in this cohort or the mild iodine deficiency that exists in this party of Australia [9].…”

“…While there were three episodes of hyperthyroidism following 131 I treatment for which the patient took ATD, none of these patients had been advised to do so by the medical teams involved, and in two of these patients the ATD was promptly stopped. 1 Number of patients who remained euthyroid throughout study period (24 mo), 2 Unsuccessful=patient remained or became biochemically and clinically hyperthyroid during follow-up, 3 Unknown=no follow-up, 4 ATD=Anti thyroid drugs (Propylthiouracil, Carbimazole).…”

“…In the presence of significant ophthalmopathy, most endocrinologists avoid the use of radioiodine, although this is controversial. Moreover, ATD are associated with significant side effects, including agranulocytosis [1,3] and some authors have suggested that their use may be obsolete [4]. On the other hand, 131 I therapy is a safe and effective treatment for GH and, in the US, approx 70% of endocrinologists would choose 131 I as first line therapy [1], but in Australia the rate is lower at 20% [2].…”

Effect of long-term continuous methimazole treatment of hyperthyroidism: comparison with radioiodine

“…In spite of almost 60 years experience in the use of antithyroid drugs and radioiodine for the treatment of Graves' disease, the rationale for choice of therapy is often obscure (6,35). Very often the choice has to be made between prolonged treatment with antithyroid drugs on the one hand and lifetime therapy with thyroid hormone for thyroid failure on the other (36).…”

“…Reports of low remission rate therapy (6,7) and ease, effectiveness and low expense of radioiodine therapy (8,9), has led to increasing reliance on radioiodine treatment for hyperthyroidism. In fact, more than two thirds of the members of the American Thyroid Association choose radioiodine as the treatment of choice for virtually all patients with Graves' disease (10).…”