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Thyroid Biology and Disease

SAT-323 - Methimazole Resistance in Graves' Disease with Concomitant Papillary Thyroid Carcinoma: A Rare Case Report

Saturday, June 13, 2026
9:30 AM - 4:30 PM CT
Location: ENDOExpo; Poster Floor
Disclosure(s):
May Shar, M.B.,B.S: No financial relationships to disclose
Background
Graves’ disease is the most common cause of thyrotoxicosis, typically managed with antithyroid drugs such as methimazole (MMI). Resistance to MMI is rare and poses a significant therapeutic challenge, particularly when thyroid malignancy coexists.

Case presentation
A 43-year-old male with untreated underlying hyperthyroidism presented with hoarseness, weight loss, diarrhea, and eye bulging. Physical examination showed a diffuse goiter with a dominant right thyroid nodule. He has a maternal family history of thyroid cancer. Thyroid function tests confirmed thyrotoxicosis with positive thyroid-stimulating immunoglobulin, consistent with Graves’ disease. Fine-needle aspiration of the nodule revealed papillary thyroid carcinoma (Bethesda VI). Despite high-dose MMI therapy (up to 40 mg/day) and good compliance, the patient remained persistently hyperthyroid, suggesting MMI resistance. Switching to propylthiouracil (PTU) resulted in significant improvement, and biochemical euthyroidism was achieved in ten weeks. He subsequently underwent an uncomplicated total thyroidectomy, and final histopathology confirmed papillary thyroid carcinoma (pT2N0aMx).

Discussion
Resistance to MMI is rare, and its underlying mechanisms remain unclear. Possible contributing factors include impaired drug absorption, rapid metabolism, and reduced intrathyroidal uptake. Clinicians should consider MMI resistance in patients with persistent hyperthyroidism despite adherence to therapy. The successful use of PTU in this context highlights the importance of considering alternative treatment options when standard treatment fails.

Conclusion
This case emphasizes an extremely rare case of papillary thyroid carcinoma coexisting with MMI-resistant Graves’ disease. Early recognition of antithyroid drug resistance and timely switch to alternative therapy are crucial to achieve euthyroidism and enable safe definitive management. Additionally, this case draws attention to the rare incidence of antithyroid drug resistance in Graves’ disease and the potential association with thyroid neoplasia, warranting further study.

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