Is Recombinant Human TSH a Trigger for Graves' Orbitopathy?

The pathogenesis of Graves' orbitopathy (GO) remains unknown. The hypothesis of a causal relationship between autoimmunity against the TSH receptor (TSHR) and GO is supported by clinical studies. Radioiodine treatment is associated with worsening or new onset of GO, possibly via antigen shedding or by inducing hypothyroidism. The coexistence of thyroid cancer with Graves' disease (GD) and GO is rare. Here we report 3 cases of reactivation of GO in patients who underwent treatment with recombinant human TSH (rhTSH) and radioiodine ablation. In each case, a thyroidectomy was performed to treat the GD, and an incidental thyroid cancer was discovered. In all 3 cases, reactivation of GO was observed 3-6 weeks after administration of rhTSH, despite maintaining euthyroidism, which was unaccompanied by a rise in serum TSHR antibodies after radioiodine and despite steroids in 1 of the 3 patients. These observations suggest that binding of either TSH or TSHR antibodies to the TSHR, independently of thyroid status, may be causally related to deterioration of GO. Clinicians should be aware of a possible association between rhTSH administration and reactivation of GO, which should be taken into account before prescribing rhTSH in patients with GO. Prophylactic steroids may need to be considered for patients at high risk of exacerbation of GO.