Background: Inflammation from oxygen free radical–production is believed to contribute to the development of Graves orbitopathy. Agents that reduce oxidation or the associated inflammation could improve symptoms of Graves orbitopathy. Selenium has antioxidant properties, and supplementation with an antioxidant has been shown to promote euthyroidism more quickly in patients with Graves disease taking methimazole (Tapazole). Preliminary evidence also has suggested that pentoxifylline (Trental) may benefit patients with Graves orbitopathy because of its anti-inflammatory and immunomodulatory effects. The European Group on Graves' Orbitopathy investigated whether selenium or pentoxifylline would benefit patients with mild Graves orbitopathy.
The Study: In this double-blind, placebo-controlled trial, patients were randomized to receive twice-daily doses of sodium selenite (100 mcg per dose), pentoxifylline (600 mg per dose), or placebo for six months. Patients were followed for a total of 12 months. Evaluations included periodic thyroid testing, as well as eye examinations performed by study-blinded ophthalmologists. A validated Graves orbitopathy–specific quality of life questionnaire also was administered. The two primary outcome measures were assessment of eye changes and quality of life based on responses to the questionnaire.
Results: A total of 152 patients (54 in the selenium group, 48 in the pentoxifylline group, and 50 in the placebo group) were included in the final analysis. Baseline traits, including thyroid status, quality of life, and severity of orbitopathy, were similar among groups. The selenium and pentoxifylline groups had significant reductions in thyroid peroxidase autoantibodies from baseline (P = .001 and .02, respectively), but the placebo group did not (P = .4).
Compared with those in the placebo group, significantly fewer patients in the selenium group reported decreased quality of life (17 versus 43 percent respectively; P = .004), and more patients showed improvements in eyelid aperture and soft-tissue involvement. These improvements persisted in the selenium group at 12 months (six months after treatment was stopped). In contrast, no benefit in quality of life or severity of orbitopathy occurred in the pentoxifylline group at any point. Seven patients in the pentoxifylline group had drug-related adverse effects (e.g., gastrointestinal symptoms, erythema, pruritus), whereas no adverse effects were noted in the selenium or placebo groups.
Conclusion: Selenium, but not pentoxifylline, resulted in significant improvements in quality of life and level of orbitopathy involvement in patients with mild Graves orbitopathy. The beneficial effects of selenium supplementation continued for at least six months after the treatment was discontinued.