SUN-572 Hyperthyroidism Refractory to Methimazole

Abstract

Background: Methimazole (MMI) inhibits oxidation and organic binding of thyroid iodine and therefore produces intrathyroidal hormone deficiency. The half-life of MMI is 6 hours but the anti-thyroidal effect lasts longer than 24 hours due to accumulation in the thyroid gland. We present a case of hyperthyroidism refractory to MMI therapy. Clinical Case: A 65-year old male with medical history of coronary artery disease and ischemic cardiomyopathy who presented to the hospital with inappropriate AICD firings in the setting of new onset Atrial fibrillation with RVR. On presentation, he endorsed 20 pounds weight loss in 3 months, palpitations and diarrhea. Physical exam revealed a slightly enlarged thyroid with rubbery texture in addition to tremors without any stigmata of Grave’s disease. Labs were remarkable for a suppressed TSH 0.03 mIU/L (reference 0.44-3.98 mIU/L), elevated free T4 4 ng/dl (reference 0.78-1.48 ng/dl), total T3 280 ng/dl (60-200 ng/dl), anti- TG ab 44 IU/ml (0-40 IU/ml), anti-TPO 12 IU/ml ( 0-34 IU/ml), undetectable TSI and normal ESR/CRP. US of the thyroid gland revealed diffuse heterogeneity as well as 2 subcentimetric nodules. Patient was treated with IV amiodarone for his atrial fibrillation and was started on MMI 20 mg bid and discharged with endocrinology follow up. He presented 10 days later with AICD firing in the setting of ventricular tachycardia resulting in cardiac arrest. Labs were significant for persistent hyperthyroidism TSH< 0.01 mIU/L, free T4 6.28 ng/dl, and total T3 330 ng/dl. Over the course of his hospital stay which lasted 4 weeks his MMI was titrated to 80 mg TID in addition to adjunctive beta blockers, prednisone, and cholestyramine; without significant clinical or biochemical improvement of hyperthyroidism. At that point, his serum MMI was checked post 60 mg dose at 1 and 2 hours which were 1.6 mcg/ml and 1.4 mcg/ml, respectively (reference 0.5-2.5 mcg/ml 1-3 hours following a single 60 mg dose) which indicated appropriate absorption. He eventually underwent total thyroidectomy. Free T4 2 days prior to surgery was 5.41 ng/dl. Pathology revealed a 30 gram multinodular goiter. Intrathyroidal MMI level was sent during surgery which was undetectable despite having serum MMI level of 1.7 mcg/ml 12 hours before surgery. Conclusion: We present a case of MMI resistant therapy after 6 weeks of treatment in a high risk cardiac patient. We postulate that the patient did not respond to MMI due to impaired intrathyroidal drug accumulation. This is a different mechanism compared to amiodarone induced resistance where enrichment of thyroid gland with iodine delays response to anti-thyroid agents. Other possible mechanisms of refractory thyrotoxicosis are drug malabsorption, rapid drug metabolism, and antidrug antibodies.