Effect of Graves’ Disease and Methimazole on Warfarin Anticoagulation

Abstract

Objective: To describe a case of Graves’ disease treated with methimazole and examine the influence of thyroid hormone alteration on warfarin anticoagulation. Case Summary: A 54-year-old man presented to the emergency department with palpitations, fatigue, weight loss, and anxiety attacks. He was taking no medications at that time. An electrocardiogram showed new onset atrial fibrillation. His thyroid profile was consistent with hyperthyroidism. The patient was admitted to the intensive care unit and started on methimazole 30 mg/day, metoprolol, enoxaparin, and warfarin 5 mg/day. Postdischarge doses of warfarin and methimazole were adjusted over the next several months based on thyroid panel results indicative of hypothyroidism. Postdischarge changes in methimazole dose caused alterations in thyroid function and intensity of anticoagulation as measured by international normalized ratio. Discussion: Interactions between warfarin and drugs that alter thyroid hormone concentrations have been reported; however, the extent and significance of the interaction between methimazole and warfarin have been inadequately described. Thyroid hormone concentrations influence the metabolic rates of proteins and, thus, can alter the amount of vitamin K–dependent clotting factors, which in turn can alter the extent of inhibition by warfarin. This may lead to changes in the intensity of anticoagulation and thereby increase the risk of thromboembolic or hemorrhagic events. Conclusions: Changes in thyroid hormone concentrations have the potential to significantly alter the extent of warfarin-induced anticoagulation. Clinicians must be aware of the need for close anticoagulation monitoring and dosage adjustment in patients receiving concomitant warfarin and methimazole. The full extent of this interaction may be delayed following a change in methimazole dose.