Current issues of ACP Journal Club are published in Annals of Internal Medicine


Radioiodine plus prednisone prevented development or progression of ophthalmopathy in patients with Graves hyperthyroidism

ACP J Club. 1998 May-June;128:71. doi:10.7326/ACPJC-1998-128-3-071

Source Citation

Bartalena L, Marcocci C, Bogazzi F, et al. Relation between therapy for hyperthyroidism and the course of Graves' ophthalmopathy. N Engl J Med. 1998 Jan 8;338:73-8.



To study the effects of methimazole, radioiodine alone, and radioiodine plus prednisone in patients who have Graves hyperthyroidism with mild or no Graves ophthalmopathy.


Randomized controlled trial with 12-month follow-up.


Pisa, Italy.


443 patients (mean age 42 y, 81% women) who had Graves disease with mild or no ophthalmopathy. Exclusion criteria were severe ophthalmopathy requiring orbital radiotherapy and glucocorticoids, large goiters requiring thyroidectomy, or contraindications to glucocorticoid treatment. Follow-up was complete.


All patients received methimazole for 3 to 4 months and were then allocated to radioiodine (120 to 150 ┬░Ci/g of thyroid tissue [ n = 150]), radioiodine followed by prednisone (0.4 to 0.5 mg/kg of body weight for 1 month followed by a tapering dose for 2 more months [ n = 145]), or continuation of methimazole (n = 148).

Main outcome measures

Development or progression and improvement of ophthalmopathy.

Main results

Progression or development of ophthalmopathy occurred in more patients who received radioiodine alone than in those who received methimazole (15% vs 3%, P < 0.001); no patients who received radioiodine and prednisone developed or had progression of ophthalmopathy (P < 0.001 for comparison with radioiodine) (Table). When ophthalmopathy was present at baseline, more patients who received radioiodine plus prednisone improved than did patients who received methimazole (67% vs 4%, P < 0.001). No patients who received radioiodine alone improved (P < 0.01 for the comparison of radioiodine with radioiodine plus prednisone). Transient development or worsening of ophthalmopathy occurred in 65% of patients who received radioiodine alone and consisted primarily of soft tissue changes, but 5% of patients developed constant diplopia that remained 12 months after therapy.


In patients who had Graves hyperthyroidism, ophthalmopathy worsened in more patients treated with radioiodine than in those treated with methimazole. Treatment with radioiodine plus prednisone prevented the development or progression of ophthalmopathy.

Source of funding: Not stated.

For article reprint: Dr. L. Bartalena, Istituto di Endocrinologia, University of Pisa, Ospedale Cisanello, Via Paradisa, 3, 56122 Pisa, Italy. FAX 39-50-578772.

Table. Progression or development of ophthalmopathy in Graves hyperthyroidism*

Therapy EER CER RRR (95% CI) ARR NNT (CI)
Methimazole vs radioiodine therapy (CER) 3% 15% 83% (53 to 93) 12% 8 ( 6 to 16)
Radioiodine and prednisone vs radioiodine therapy (CER) 0% 15% 100% 15% 7 (5 to 11)

*Abbreviations defined in Glossary; RRR, NNT, and CI calculated from data in article.


Most endocrinologists in the United States consider radioiodine to be the treatment of choice for Graves hyperthyroidism, except during pregnancy. Graves ophthalmopathy, which may produce periorbital edema, chemosis, proptosis, diplopia, or blindness, is a separate aspect of Graves disease, and its progression may not parallel that of hyperthyroidism. Whether exacerbation of ophthalmopathy is more likely with radioiodine treatment than with methimazole treatment has been debated, and experienced clinicians point out that development of clinically important ophthalmopathy after radioiodine therapy is unusual (1).

Bartalena and colleagues show that development or worsening of ophthalmopathy is more common after treatment with radioiodine alone than after treatment with methimazole and that the addition of a fairly high dose of prednisone for 3 months not only prevents exacerbation of eye disease but improves ophthalmopathy in most patients who had the disorder before radioiodine therapy.

Most ophthalmopathy that occurred after treatment with radioiodine alone consisted of soft-tissue changes only and no loss of vision. However, 5% of patients in this group developed persistent diplopia. After treatment with radioiodine alone, ophthalmopathy worsened in 24% of patients with preexisting eye disease. Ophthalmopathy developed in 8% of the 78 patients who did not have the disorder at baseline but was transient in all but 1 patient.

I do not believe that the slight benefit of adding prednisone to radioiodine outweighs the adverse effects of radioiodine in patients without ophthalmopathy. However, in patients with clinically important eye disease, especially those with diplopia, prednisone prevents worsening in one fourth of patients and alleviates symptoms in most. Further studies should assess whether equivalent benefits can be achieved by starting prednisone therapy after ophthalmopathy worsens.

William E. Clutter, MD
Washington University School of MedicineSt. Louis, Missouri, USA


1. Gorman CA. Therapeutic controversies. Radioiodine therapy does not aggravate Graves' ophthalmopathy. J Clin Endocrinol Metab. 1995;80:340-2.