Endocrine Abstracts

Introduction: The treatment of Graves’ disease is represented principally by anti-thyroid drugs, radioiodine ablation or thyroidectomy. Methimazole is the most used drug for the initial treatment. It is rare to encounter patients with resistant hyperthyroidism despite high doses of MMI.

Case presentation: A 41-year-old woman was referred to our unit for resistant thyrotoxicosis. She had a confirmed Graves’ disease with positive serum Trab. Whilst her MMI dose had been increased to 60 mg/day, in adjunction with prednisone therapy (70 mg/day), her serum free thyroxin concentration was too high to be measured (> 100 pmol/l). No adverse effects were noted. The patient did not show any symptoms or signs of gastrointestinal or liver disease, and had good drug compliance. Additional therapy with inorganic iodine (Lugol solution 10 drops 3 times /day) was initiated and she underwent a therapeutic plasma exchange. After 10 days, the patient’s serum free thyroxin concentration normalized, and total thyroidectomy was then performed.

Discussion: It is rarely reported that cases of Graves’ disease show no response to a very high dose of MMI and corticosteroid therapy. By preventing the iodination of tyrosine residues in thyroglobulin by thyroid peroxidase, MMI inhibits thyroid hormone synthesis. A previous clinical study showed that a high dose of MMI (120 mg/day) reduces thyroid hormone concentration more rapidly than standard doses of MMI in patients with hyperthyroidism. However, such a high dose of MMI may increase the risks of severe adverse effects. Therefore, we decide to maintain the MMI dose of 60 mg/day for our patient. Although previous cases of Graves’ disease with resistance to antithyoid drugs has been reported, the underlying mechanisms remain unclear. Inorganic iodine inhibits the release of thyroid hormone from the thyroid gland, and corticosteroids work by suppressing the conversion of T4 to T3 in peripheral tissues. The Japan Thyroid Association and the Japan Endocrine Society recommended strategy is combination of MMI with corticosteroid and inorganic iodine in preparation for a thyroidectomy.

Conclusion: We reported a rare case of Graves’ disease that was resistant to MMI. Combination therapy of MMI with corticosteroid, inorganic iodine and therapeutic plasma exchanges may represent a therapeutic option for the preoperative preparation.

References: Wiberg-JJ et al. Methimazole toxicity from high doses. Ann Intern Med 1972;77:414–416. Yusaku-Mori et al. Very rare case of Graves’ disease with resistance to methimazole: a case report and literature review. 2021 Journal of International Medical Research 49(3)1–9.