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Selenium Found to Improve Mild Graves’ Orbitopathy

Treating Milder Forms of Graves’ Orbitopathy

The most common form of hyperthyroidism is Graves’ disease, and about 1/2 of patients with this disease have ocular involvement in the form of Graves’ orbitopathy (GO). An autoimmune inflammatory disorder affecting the orbit around the eye, GO is characterized by upper eyelid retraction, swelling, redness, conjunctivitis, and bulging eyes. Moderately severe and active forms of this disease can be effectively treated with glucocorticoids and/or orbital irradiation.

Since milder forms may improve spontaneously, the usual treatment is use of artificial tears, ointments, and prisms simply to control symptoms. However, a ‘wait-and-see’ strategy in which patients are monitored until symptoms worsen, can be challenged.

First, many patients with even mild forms of GO have a substantial decrease in their quality of life, as assessed by a Graves’ orbitopathy-specific quality-of-life questionnaire. Second, a natural history study of mild GO, found that spontaneous improvement occurred in about 20% of patients, while the disease remained static in 65% and progressed in 15%. Thus, some believe that therapy would be justified.

Oxidative Stress, Selenium and Graves’

A number of in vitro studies have suggested that increased generation of oxygen free radicals and cytokines play a role in GO. Because the trace mineral selenium is a co-factor for antioxidant enzymes and has an important effect on the immune system, researchers representing the European Group on Graves’ Orbitopathy investigated whether selenium or the anti-inflammatory agent pentoxifylline might be beneficial in patients with mild GO. Their findings, published in the May 19th issue of NEJM, indicate that selenium is clinically useful in this condition.

Design

This randomized, double-blind, placebo-controlled trial was carried out in 159 patients with mild Graves’ orbitopathy. The patients received 2x daily: selenium (100 μg), pentoxifylline (600 mg), or placebo for 6 months and were then followed for 6 months after treatment was withdrawn. Primary outcomes at 6 months were evaluated by means of an overall ophthalmic assessment, conducted by an ophthalmologist who was unaware of the treatment assignments, & a GO–specific quality-of-life questionnaire, completed by the patient.

Results

At the 6-month evaluation, treatment with selenium, but not with pentoxifylline, was associated with an improved quality of life (p<0.001), less eye involvement (p = 0.01), and slower disease progression (p = 0.01), compared with placebo. The Clinical Activity Score decreased in all groups, but the change was significantly greater in the selenium-treated patients. Exploratory evaluations at 12 months confirmed the results seen at 6 months.

Two patients assigned to placebo and 1 assigned to pentoxifylline required immunosuppressive therapy for deterioration in their condition. No adverse events were evident with selenium, whereas pentoxifylline was associated with frequent gastrointestinal problems.

Comments

In this study, supplemental selenium significantly improved quality of life, reduced ocular involvement, and slowed progression of the disease, suggesting clinical utility of this mineral in treating milder forms of GO.

Reference: Marcocci C, et al. Selenium and the course of mild Graves’ Orbitopathy. NEJM 364:1920-31, 2011.