To the Editor:
We read with interest the letter by van Lieshout, et al1, describing a 70-year-old woman who developed Graves’ disease while being treated with anti-tumor necrosis factor-α (anti-TNF-α; adalimumab) for active rheumatoid arthritis (RA). They suggested an association of autoimmune thyroid disease with various autoimmune diseases including RA, but could not conclude whether there is a relationship between symptoms of Graves’ disease and anti-TNF-α1.
We previously reported an association of Henoch-Schonlein purpura and Graves’ disease2, but immunosuppression itself (e.g., cyclosporine) might also be a precipitating factor for the development of Graves’ disease3. Hofle, et al had also showed that immunosuppressive therapy consisting of cyclosporin A and prednisolone could cause development of Graves’ disease in a transplant recipient by abnormal modulation of the immune system4.
Although there are no extensive studies in patients with RA treated with anti-TNF-α, Allanore, et al5 recently described a 37-year-old woman who developed transient hyperthyroidism while being treated with anti-TNF-α (etanercept) for active RA, and this case may be very similar to that described by van Lieshout et al1. Allanore, et al speculated that the production of (1) non-neutralizing antibodies directed against the etanercept molecule (16% of patients taking the drug), (2) anti-double-stranded DNA antibodies (15% of treated patients) or antinuclear antibodies (11%), and (3) anti-animal antibodies might cause an autoimmune reaction through cross-reactive immunogenicity to the thyroid gland, which seems to be very sensitive to autoimmunity.5
Therefore, careful thyroid-function monitoring would be necessary during immunosuppressive or anti-TNF-α therapy, and further studies should be performed to elucidate the pathogenesis of Graves’ disease in patients receiving anti-TNF-α therapy.