University of Michigan
Department of Pediatrics
Evidence-Based Pediatrics Web Site

Question

• 17 y/o girl with Grave's disease and proptosis comes into your office. Are children with Grave's disease likely to have worsening of their eye findings after receiving radioactive iodine as compared with antithyroid drugs?

Clinical Bottom Lines

1. Patients treated with radioiodine for Grave's disease are more likely to have worsening of eye findings when compared with those patients who treated with radioiodine plus prednisone or methimazole. Number Needed to Harm=7.
2. Patients are more likely to have regression of their eye findings if treated with radioiodine plus prednisone compared with those who treated with radioiodine alone or methimazole. Number Needed to Treat=2

Summary of Key Evidence

1. 450 patients with Grave's disease (characterized by hyperthyroidism, diffuse goiter, and thyroid autoantibodies in serum) were randomized in a single-blind study to receive radioiodine, radioiodine plus prednisone, or methimazole. The three groups had similar baseline characteristics.¹
2. Outcome measures were based on ocular exams that were carried out every one to two months by a single examiner. The appearance, progression, or regression of eye findings was based on major and minor criteria that were outlined in the methods section. Analysis was based on intention to treat.
3. 150 patients treated with radioiodine alone, eye findings worsened in 23 (15% - CI 10-22%). Of the 145 patients in the radioiodine plus prednisone group, no patients had worsening/development of ophthalmopathy. Of the 148 patients who were treated with methimazole, 4 (3%) had worsening of eye findings. The patients in the radioiodine group alone had a significant rate of worsening of eye disease compared with the other two groups (p< 0.001).
4. 50/75 (67% CI 55-77%) patients in the radioiodine plus prednisone group who had ophthalmopathy at baseline showed improvement. No patients in the radioidodine
   group alone showed improvement. Only 3/74 (4% CI 1-11%) patients in the methimazole showed improvement in eye findings (p<0.001).
5. The radioiodine groups (with and without steroids), the patients with preexisting ophthalmopathy were more likely to have worsening of their disease, compared with those patients with no previous eye findings.

Additional Comments

• Limitations of the study-- there was no baseline data recorded when the patients were diagnosed - only at after 3-4 months of treatment with methimazole. This is a significant limitation because we don't know what these patients looked like when initially diagnosed - i.e. what were their levels of T4 and what their physical exam showed.
• Not sure if the eye findings are clinically significant - do patients truly notice differences of two mm?
• There has been a concern in the past about giving children radioactive iodine - does it increase rates of leukemia, carcinoma of the thyroid, or genetic damage to future children for women who are in their childbearing years? Multiple longitudinal articles have shown that these concerns are unfounded.
• A very real side effect of giving radioactive iodine for the treatment of Graves' disease is the induction of hypothyroidism (62%-66% of time) - which will have to be treated for life.
• The prevalence of smokers was greater among those patients who had worsening of ophthalmopathy
• Relapse rates of hyperthyroidism when treated by antithyroid drugs occurs 54-58% of time.²
• Lowest rates of relapse after being treated with antithyroid drug is in patients with a small goiter or very minimal changes in thyroid function at time of diagnosis.³
  

Citation

1. Bartalena L, Marcocci C, et al. Relation between therapy for hyperthyroidism and
   the course of Graves' Ophthalmopathy. N Engl J Med 1998; 338: 73-8.
2. Abraham P, Avenell A, et al. Cochrane Database of Systematic Reviews: Antithryoid Drug
   Regiment for treating Graves' hyperthyroidism. The Cochrane Library 2004; Vol 3.
3. Cooper D. Antithyroid Drugs in the Management of Patients with Graves' Disease: An
   Evidence - Based Approach to Therapeutic Controversies. J Clin Endocrin Metab 2003; 88: 3474-81.

CAT Author: Amanda Osta, MD

CAT Appraisers: Robert Schumacher, MD

Date appraised: November 17, 2004