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Previously, we described a case of ipilimumab-induced orbital inflammatory syndrome resembling euthyroid inflammatory Graves disease1,2 Subsequently, others have described similar cases3,4 The original case was associated with positive antithyroid antibodies despite the euthyroid states. This patient, 2 years after the diagnosis and with continued exposure to ipilimumab, developed anxiety, palpitations, and 14-pound weight loss without anorexia, diarrhea, lethargy, and heat intolerance. The T3 was highly elevated at 244 and T4 at 4.8; thyroid peroxidase antibodies were elevated at 2,047 and with elevated antithyroglobulin antibodies at 64.Development of full-blown systemic hyperthyroidism in the original patient described with ipilimunab-associated inflammatory orbitopathy provides further evidence of CTLA-4 suppression in the mechanism of Graves disease. Patients with this syndrome should be followed for systemic hyperthyroidism after the orbital inflammatory presentation.Gary E. Borodic, M.D.David Hinkle, M.D.