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

Context: Glucocorticoids are effective for severe Graves' orbitopathy ( GO), which causes substantial morbidity. The question at issue is how best to use them. Objective: The objective of this study was to optimize glucocorticoid application in GO. Design: The study design was a randomized trial over 12 wk with 6-month follow-up. Setting: The study was performed at university joint thyroid and ophthalmic clinics. Patients: Seventy euthyroid out-patients with untreated, active, and severe GO were studied. Intervention: 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. Main Outcome Measures: 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. Results: 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). Conclusions: In patients with active and severe GO, iv glucocorticoids were more effective and better tolerated than oral steroids.