Kenya Kasahara, Hanako Nakajima, Hiroshi Okada, Masahide Hamaguchi, Michiaki Fukui
Graves' disease can be managed with antithyroid drugs (ATDs), radioactive iodine (RAI), or surgery. When ATDs are ineffective or poorly tolerated, RAI or surgery may be indicated. Methimazole (MMI) and propylthiouracil (PTU) are commonly used, sometimes with adjunctive agents such as potassium iodide (KI), β-blockers, or corticosteroids. Although ATDs are essential in management, rare but severe allergic reactions may occur, necessitating careful monitoring. We report a case of refractory Graves' disease with a history of ATD-induced hemophagocytic syndrome and multiple drug allergies. A 43-year-old woman was diagnosed with Graves' disease after presenting with thyrotoxicosis and was treated with MMI and KI. Following an increase in the MMI dosage, she developed a rash and was switched to PTU. Although the rash resolved, she developed fever requiring hospitalization. During admission, shock and abnormal vital signs prompted suspicion of PTU-induced hemophagocytic lymphohistiocytosis. Immunosuppressive therapy, plasma exchange, temporary hemodialysis, and corticosteroids led to improvement. She was discharged on corticosteroids, but thyroid function worsened during tapering, making ATDs unsuitable. Sixteen months later, RAI therapy was attempted; thyroid function worsened, and KI was continued. Eighteen months later, she was rehospitalized for fatigue; increasing corticosteroids improved thyroid hormone levels. Due to multiple drug allergies, a drug-induced lymphocyte stimulation test was performed preoperatively and was positive for levothyroxine (LT4), although patch and oral provocation tests were negative, confirming LT4 safety. After stabilization, total thyroidectomy was performed; postoperatively, she received powdered LT4 and calcium supplementation. The course was uneventful, without allergic manifestations, and she was discharged in good condition. This case highlights the risk of severe hematologic complications from PTU and demonstrates that, with careful preoperative evaluation and individualized perioperative management, safe surgical treatment of refractory Graves' disease is possible.