Oral selenium significantly improves patients’ quality of life and slows the progression of mild Graves’ orbitopathy, according to the findings of a year-long randomized controlled trial.
In an international randomized clinical trial comparing the drug with placebo and pentoxifylline tablets, only selenium improved both visual functioning and appearance, mainly by ameliorating soft-tissue changes and reducing eyelid aperture, said the department of endocrinology and metabolism at the University of Pisa (Italy) in the European group on Graves’ orbitopathy.
Selenium (an antioxidant) and pentoxifylline (an anti-inflammatory) were chosen as potentially therapeutic agents to test in this trial because in vitro and small pilot studies have suggested that they might be beneficial in Graves’ orbitopathy.
In all, 152 patients in Italy, Netherlands, Germany, Greece and Switzerland were randomly assigned to receive selenium (54 subjects), pentoxifylline (48 subjects), or placebo (50 subjects) for six months and were followed at intervals for one year to assess outcomes. Selenium and placebo tablets were prepared to look the same as pentoxifylline.
The study subjects had only mild signs or symptoms of orbitopathy at baseline, and had been affected for less than 18 months. Scores on the Graves’ orbitopath-specific quality of life (QOL) questionnaire were similar among the groups at baseline, showing mild to moderate impairment. Scores on measures of visual functioning and appearance also were comparable at baseline.
At six months, QOL scores improved significantly only in the patients who received selenium. Visual functioning improved significantly in 62% and appearance improved significantly in 75% of that group. No such improvements were reported in the other two study groups.
Moreover, the patients who were treated with selenium had a substantially lower rate of worsening of QOL (9 of 53 patients, or 17%) compared with those given placebo (20 of 46 patients, or 43%).
“The overall ophthalmic outcome at the 6-month evaluation was significantly better in the selenium group than in the placebo group (P=. 01), whereas there was no significant difference between the pentoxifylline and placebo groups (P = .12).”
Improvements in eyelid aperture and in soft-tissue involvement, rather than changes in proptosis and eye motility were the major determinants of the overall ophthalmic outcome in patients treated with selenium,”
The median reduction in eyelid aperture was two mm at six months and 3 mm at one year.
Although the Clinical Activity Score was significantly lower in the selenium group than in the other two groups at 6 months, this score declined in all three groups, “probably reflecting the natural history of mild Graves’ orbitopathy, which becomes less active or inactive in most cases .”
“The beneficial effect of selenium on QOL and the overall eye evaluation persisted for 6 months after therapy was withdrawn.”
There were no drug-related adverse effects reported for either selenium or placebo.
However, seven patients who were taking pentoxifylline reported skin and gastrointestinal disorders, and four of them dropped out of the study during the first months.
The precise mechanism by which selenium exerted these benefits is not yet known, but “we speculate that an intervention aimed at improving the antioxidant-oxidant balance might be helpful in both hyperthyroidism and Graves’ orbitopathy.”
The study was limited in that there were no data on actual changes in serum selenium levels.