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Amiodarone-induced thyrotoxicosis (AIT) is a potentially life-threatening complication of amiodarone therapy, particularly hazardous in patients with underlying structural heart disease. We report the case of a man in his mid-60s with severe cardiomyopathy and recurrent ventricular tachycardia who developed refractory thyrotoxicosis following amiodarone exposure. Overlapping features of type 1 and 2 AIT suggested mixed-type disease, posing a significant diagnostic challenge. Despite aggressive conventional therapy with high-dose thionamides and glucocorticoids, supplemented by adjunctive agents, including lithium and cholestyramine, thyrotoxicosis remained refractory and life-threatening arrhythmias persisted. Given the high cardiac risk and refractory disease course, total thyroidectomy was undertaken as definitive management; therapeutic plasma exchange was used as bridging therapy to achieve rapid biochemical improvement and minimise perioperative risk. This case highlights the complexity of managing severe, treatment-refractory AIT and underscores the value of multidisciplinary care and plasmapheresis as a bridging strategy prior to definitive surgical management.