We studied the effects of radioiodine treatment of hyperthyroidism due to Graves' disease on Graves' ophthalmopathy and the possible protective role of corticosteroids. Between June 1985 and June 1988, 26 patients were randomly assigned to treatment with radioiodine alone (group 1) and 26 to treatment with this agent and concomitant administration of systemic prednisone for four months (group 2). The initial dose of prednisone was 0.4 to 0.5 mg per kilogram of body weight for one month; the drug was gradually withdrawn over the next three months. All patients were evaluated at 3-month intervals for 18 months after they underwent radioiodine therapy. Ocular changes were assessed with the ophthalmopathy index; patients with moderate-to-severe changes (scores greater than or equal to 4) were excluded from the study. Before treatment, 10 patients in group 1 and 5 in group 2 had no evidence of ophthalmopathy: in none of them did ocular symptoms appear after radioiodine therapy. Among the patients in group 1 with an initial ophthalmopathy index greater than or equal to 1, ocular disease worsened in 56 percent (mostly involving soft-tissue changes and extraocular-muscle function) and did not change in 44 percent. In contrast, ophthalmopathy improved in 52 percent and did not change in 48 percent of group 2. The mean ophthalmopathy index increased from 1.5 to 3.0 in group 1 (P less than 0.005) and decreased from 2.2 to 1.3 in group 2 (P less than 0.05). We conclude that systemic corticosteroid treatment prevents the exacerbations of Graves' ophthalmopathy that occur after radioiodine therapy in a substantial proportion of patients with hyperthyroidism who have some degree of ocular involvement before treatment.

Since a relationship between cigarette smoking and the occurrence of Graves' ophthalmopathy has been recently postulated, we reviewed the smoking habits of 1730 women, including subjects without thyroid disease, with nontoxic goiter (NTG), toxic nodular goiter or toxic adenoma (TNG), Hashimoto's thyroiditis (HT), Graves' disease without ophthalmopathy (GD) or with ophthalmopathy (GO). The prevalence of smokers in NTG, TNG and HT was about 30%, not different from that of controls. Smokers were 47.9% in GD and 64.2% in GO groups. The latter figures were highly different from those of the other groups and also from each other. The percentage of heavy smokers was higher in patients with more severe ophthalmopathy. No clear explanation for this phenomenon can be offered. The absence of a high prevalence of smokers among patients with non-toxic goiter, nonautoimmune hyperthyroidism and Hashimoto's thyroiditis, limits the impact that smoking might have had in the pathogenesis of goiter, hyperthyroidism and autoimmune phenomena of GD and GO.

Abstract. Eye disease was associated with hyperthyroidism in 202 of 221 patients with active Graves' ophthalmopathy (91.4%) and was not accompanied by thyroid hyperfunction (euthyroid Graves' disease) in the remaining 19 (8.6%). All the latter patients had some mild thyroid abnormalities (thyroid autoantibodies, negative TRH test, negative T3 suppression test, goitre). Sex distribution analysis evidenced a higher prevalence in females with a female/male ratio of 2.1 which was, however, significantly lower (P < 0.05) than that observed in control (Graves' disease patients without overt ophthalmopathy (female/male ratio = 3.4)). Patients with euthyroid Graves' disease showed a female/male ratio of 0.7. Age distribution revealed a peak prevalence in the 5th decade of life, identical to that of Graves' disease without ophthalmopathy. A close temporal relationship between the onset of hyperthyroidism and the onset of ophthalmopathy was found, since in about 85% of the patients the first ocular manifestations occurred within ±18 months around the onset of hyperthyroidism.

Combined therapy with systemic corticosteroids and orbital cobalt radiotherapy has been shown to be an effective treatment of severe Graves' ophthalmopathy. The potentially serious side-effects of large doses of systemic corticosteroids prompted us to evaluate the use of retrobulbar corticosteroids instead of systemic corticosteroids. Forty-four patients with active Graves' ophthalmopathy were given orbital cobalt irradiation (total dose 2000 rads) and retrobulbar methylprednisolone acetate (14 bilateral injections at 20-30 d intervals). The degree of ocular involvement and responses to treatment were evaluated by numerical scoring (ophthalmopathy index, OI) and clinical assessment. Excellent or good responses were observed in 11 out of 44 patients (25%), 24 (55%) showed slight responses, and no change was found in 9 patients (20%). The initial OI mean score was 5.9; the final score was 3.2, with a change of -2.7 (P less than 0.001). Regression or partial improvement was observed in most cases (35/44, 80%) with soft tissue changes, and in all 9 cases with sight loss due to optic neuropathy. Proptosis, corneal lesions and extra-ocular muscle involvement were less responsive, since regression or partial improvement was observed in 39% (12/31), 50% (8/16) and 31% (13/42), respectively. No major side-effects were observed. The effects of this type of therapy and those obtained by combined therapy with systemic corticosteroids and orbital radiotherapy were compared in two groups of 30 patients each, randomly assigned to either treatment.(ABSTRACT TRUNCATED AT 250 WORDS)

Orbital radiotherapy and corticosteroids are two well-established medical treatments for severe Graves’ ophthalmopathy. In this report we analyze the results obtained by the combination of orbital radiotherapy and systemic or retrobulbar corticosteroids in patients with severe Graves’ ophthalmopathy. Orbital cobalt radiotherapy was carried out by a cobalt unit, delivering a total of 2,000 rads to each eye in 10 daily doses. Systemic corticosteroid treatment was started with 70–80 mg methylprednisolone/day for 2–3 weeks with subsequent progressive reduction of the dose until discontinuation of the drug after 5–6 months. Retrobulbar corticosteroid therapy was performed by 14 bilateral injections of 40 mg methylprednisolone acetate at 20- to 30-day intervals. Results were evaluated both on clinical grounds and by numerical scoring (ophthalmopathy index, OI). Excellent or good responses were obtained in the majority of 72 patients by combined treatment with orbital cobalt radiotherapy and systemic corticosteroids. Soft tissue changes, newly developed eye muscle dysfunction and optic neuropathy showed the most beneficial effects from treatment, whereas proptosis, corneal lesions and long-standing eye muscle abnormalities responded to a lesser extent. The results of a controlled clinical trial showed that the combined treatment was more effective than the administration of systemic methylprednisolone alone. Because relevant side effects of systemic corticosteroid therapy were observed in 4 cases, the clinical validity of retrobulbar corticosteroids in substitution for systemic corticosteroids was evaluated in 44 patients. Excellent or good responses were observed in 25% of these patients, slight responses being obtained in 55% and no change in 20%. Regression or partial improvement was observed in most cases with soft tissue changes and optic neuropathy, while proptosis, corneal lesions and extraocular muscle involvement were less responsive. The results of combined treatment with orbital radiotherapy and systemic or retrobulbar corticosteroids were directly compared in two groups of patients, giving more satisfactory results in the former group, both on clinical grounds and in terms of changes of the OI. In conclusion, retrobulbar corticosteroids associated with orbital radiotherapy are not as effective as systemic corticosteroids combined with orbital irradiation in the treatment of Graves’ ophthalmopathy. Thus, we limit the use of retrobulbar steroids to patients with contraindications to the systemic administration of steroids.