Randomized, single blind trial of intravenous versus oral steroid monotherapy in Graves' orbitopathy.

Abstract

Glucocorticoids are effective for severe Graves' orbitopathy (GO), which causes substantial morbidity. The question at issue is how best to use them. The objective of this study was to optimize glucocorticoid application in GO. The study design was a randomized trial over 12 wk with 6-month follow-up. The study was performed at university joint thyroid and ophthalmic clinics. Seventy euthyroid out-patients with untreated, active, and severe GO were studied. Patients received either once weekly iv methylprednisolone (0.5 g, then 0.25 g, 6 wk each) or oral prednisolone starting with 0.1 g/d, then tapering the dose by 0.01 g/wk. At 3 months, the primary end point was a composite of improvements in proptosis, lid fissure width, and rate of diplopia in primary gaze, visual acuity, eye muscle thickness, and patient's quality of life. Intravenous glucocorticoid therapy resulted in rapid, significant, and sustained improvement. At 3 months, 27 of 35 patients (77%) in the iv group had a treatment response compared with 18 of 35 (51%) in the oral group (P < 0.01). Improvements over baseline values for disease severity (e.g. visual acuity; P = 0.01) and activity (e.g. chemosis; P < 0.01) and for quality of life (P < 0.001) were greater in the iv group. TSH receptor antibody titers decreased during iv steroid administration (P < 0.001), and smoking had a strong impact on the therapy response (P < 0.001). Additional treatment was required less frequently in the iv group. Intravenous steroids were safe, with different rates of adverse events between the two groups (P < 0.001). In patients with active and severe GO, iv glucocorticoids were more effective and better tolerated than oral steroids.