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Thyroid-Associated Ophthalmopathy after Treatment for Graves’ Hyperthyroidism with Antithyroid Drugs or Iodine-131

Departments of Endocrinology (E.N.), Oncology (G.B.), and Ophthalmology (T.A.), Sahlgrenska University Hospital, SE-413 45 Gothenburg, Sweden; Departments of Endocrinology (P.H.) and Ophthalmology (V.P.), Lund University Hospital, SE-221 85 Lund, Sweden; Departments of Endocrinology (B.H., M.L.) and Ophthalmology (P.Å.), Malmoe University Hospital, SE-205 02 Malmoe, Sweden; Department of Oncology, Radiumhemmet (G.L.), Department of Molecular Medicine and Surgery, Division of Surgery (G.W.), and Department of Endocrinology (J.C.), Karolinska University Hospital, Karolinska Institute, SE-141 86 Stockholm, Sweden; Department of Clinical Neurosciences (L.T., F.T.), St. Erik Eye Hospital, Karolinska Institute, SE-112 82 Stockholm, Sweden; Department of Clinical Research and Education, Karolinska Institute and Department of Internal Medicine, Division of Endocrinology, (O.T.), Södersjukhuset, SE-118 83 77 Stockholm, Sweden; Department of Clinical Sciences, Division of Surgery (M.A.-N.), Danderyd Hospital, Karolinska Institute, SE-171 77 Stockholm, Sweden; and Department of Information Science (A.T.), University of Uppsala, SE-751 20 Uppsala, Sweden

Address all correspondence and requests for reprints to: Frank Träisk, M.D., Ph.D., Department of Clinical Neurosciences, Karolinska Institute, St. Erik Eye Hospital, Polhemsg. 50, SE-11282, Stockholm, Sweden. E-mail: frank.traisk{at}sankterik.se.

Context: Previous randomized trials have suggested an association between radioiodine treatment for Graves’ hyperthyroidism and thyroid-associated ophthalmopathy (TAO).

Objectives: The aim of the study was to compare the occurrence of worsening or development of TAO in patients who were treated with radioiodine or antithyroid drugs.

Design: We conducted a randomized trial (TT 96) with a follow-up of 4 yr.

Patients, Setting, and Intervention: Patients with a recent diagnosis of Graves’ hyperthyroidism were randomized to treatment with iodine-131 (163 patients) or 18 months of medical treatment (150 patients). Early substitution with T₄ was given in both groups.

Main Outcome Measure: Worsening or development of TAO was significantly more common in the iodine-131 treatment group (63 patients; 38.7%) compared with the medical treatment group (32 patients; 21.3%) (P < 0.001).

Results: The risk for de novo development of TAO was greater in patients treated with iodine-131 (53 patients) than with medical treatment (23 patients). However, worsening of TAO in the 41 patients who had ophthalmopathy already before the start of treatment was not more common in the radioiodine group (10 patients) than in the medical group (nine patients). Smoking was shown to influence the risk of worsening or development of TAO, and smokers treated with radioiodine had the overall highest risk for TAO. However, in the group of smokers, worsening or development of TAO was not significantly associated with the choice of treatment for hyperthyroidism.

Conclusions: Radioiodine treatment is a significant risk factor for development of TAO in Graves’ hyperthyroidism. Smokers run the highest risk for worsening or development of TAO irrespective of treatment modality.