Comparison of the effectiveness and tolerability of intravenous or oral glucocorticoids associated with orbital radiotherapy in the management of severe Graves' ophthalmopathy: Results of a prospective, single-blind, randomized study

Eighty-two consecutive patients with moderate-to-severe and active Graves' ophthalmopathy were randomly treated with orbital radiotherapy combined wit h either oral (prednisone; starting dose, 100 mg/d; withdrawal after 5 mont hs) or iv (methylprednisolone; 15 mg/kg for four cycles and then 7.5 mg/kg for four cycles; each cycle consisted of two infusions on alternate days at 2-wk intervals) glucocorticoids. The two groups did not differ for age, ge nder, duration of hyperthyroidism and ophthalmopathy, prevalence of smokers , thyroid volume, and pretreatment ocular conditions. Both groups of patien ts received radioiodine therapy shortly before treatment for Graves' ophtha lmopathy. Follow-up lasted for 12 months. A significant reduction in proptosis (from 23.2 +/- 3.0 to 21.6 +/- 1.2 mm in the iv glucocorticoid group, P < 0.0001; and from 23 +/- 1.8 to 21.7 +/- 1.8 min in oral glucocorticoid group, P < 0.0001) and in lid width (from 1 3.3 +/- 2.5 to 11.8 +/- 2.2 mm, and from 13.6 +/- 2.0 to 11.5 +/- 1.9 mm, r espectively; P < 0.001 in both cases) occurred, with no difference between the two groups. Diplopia significantly improved in both groups: it disappea red in 13 of 27 (48.1%) iv glucocorticoid patients (P < 0.005) and in 12 of 33 (36.4%) oral glucocorticoid patients (P < 0.03). The degree of ameliora tion of diplopia did not significantly differ between the two groups (P = 0 .82). Optic neuropathy improved in 11 of 14 iv glucocorticoid (P < 0.01) an d only in 3 of 9 oral glucocorticoid (P = 0.57) patients, with no significa nt difference in these outcomes. The Clinical Activity Score decreased from 4.5 +/- 1.2 to 1.7 +/- 1.0 (P < 0.0001) in the iv glucocorticoid group and from 4.2 +/- 1.1 to 2.2 +/- 1.2 (P < 0.0001) in the oral glucocorticoid gr oup; final Clinical Activity Score was significantly lower in iv glucocorti coid than in oral glucocorticoid patients (P < 0.01). By self-assessment ev aluation, 35 (85.3%) iv glucocorticoid and 30 (73.2%) oral glucocorticoid p atients reported an improvement of ocular conditions (P = 0.27). Overall, b oth treatments produced favorable effects in most patients, but responders in the iv glucocorticoid group (36 of 41, 87.8%) were more than in the oral glucocorticoid group (26 of 41, 63.4%) (P < 0.02). Moreover, iv glucocorti coid treatment was better tolerated than oral glucocorticoid treatment. Sid e effects occurred in 23 (56.1%) iv glucocorticoid. and 35 (85.4%) oral glu cocorticoid patients (P < 0.01); in particular, cushingoid features develop ed in 5 of the former and 35 of the latter patients. One iv glucocorticoid patient had severe hepatitis of undetermined origin at the end of glucocort icoid treatment, followed by spontaneous recovery. In conclusion, high-dose iv glucocorticoid and oral glucocorticoid (associa ted with orbital radiotherapy) are effective in the management of severe Gr aves' ophthalmopathy, but the iv route seems to be more effective and bette r tolerated than the oral route and associated with a lower rate of side ef fects.