The Paralysis That Wouldn’t Quit: A Hyperthyroid Crisis Resistant to Methimazole

Introduction: Graves' disease is an autoimmune condition causing excess thyroid hormone due to TSI stimulation. A rare complication, thyrotoxic periodic paralysis (TPP), typically affects young males and presents as painless muscle weakness from hypokalemia. It’s managed with potassium replacement, beta-blockers, and antithyroid medication. Methimazole is first-line, but resistance—though rare—can hinder treatment, requiring alternatives like Propylthiouracil or definitive therapy with iodine ablation or thyroidectomy. We report a case of recurrent TPP in a young male with suspected methimazole resistance and persistent thyrotoxicosis.


Description: A 22-year-old male with known history of Grave's Disease previously only on propranolol was admitted to the intensive care for thyroid storm with severe muscle weakness attributed to severe hypokalemia (1.6 mmol/L). The patient was treated with rapid potassium replacement and started on beta blockers, methimazole and hydrocortisone and eventually discharged. Patient had a subsequent readmission with similar presentation despite the use of methimazole with dose adjustment. Methimazole resistance was suspected and the decision to transition to propylthiouracil was made. His thyroid function tests normalized and definitive treatment with ablation or surgery was recommended.


Discussion: Thyrotoxic periodic paralysis (TPP) is a potentially life-threatening manifestation of thyrotoxicosis. It results from intracellular potassium shifts driven by elevated thyroid hormone levels and heightened adrenergic stimulation. Although more common in Asian populations, TPP can affect individuals of any ethnicity and occurs disproportionately in males. Our patient experienced multiple episodes of TPP despite adherence to methimazole which raised concerns for possible resistance. Methimazole resistance is rare with mechanisms not well understood but can involve impaired intrathyroidal drug accumulation or increased thyroid hormone turnover. Our patient's response to propylthiouracil further supports the case of methimazole resistance. Definitive therapy with surgery or iodine ablation should always be recommended in these cases. Prompt recognition of possible methimazole resistance is key to avoid recurrent thyrotoxicosis, including hypokalemic period paralysis.