FRI516 Low Dose Methimazole Induced Isolated Thrombocytopenia

Abstract

Abstract Disclosure: F. Amer: None. S. Ghaith: None. S. Kadiyala: None. M. Xhikola: None. Background: Thionamides can lead to agranulocytosis in 0.1 - 0.5% of patients. This is a severe adverse reaction due to inhibition of myelopoiesis. The proposed mechanism of bone marrow suppression is thought to be due to direct toxicity and/or immune mediated. For methimazole this side effect is seen with doses > 30 mg/day. This is a case of isolated thrombocytopenia in a patient treated with low dose methimazole. Clinical case: 69-year-old man diagnosed with Graves’ disease about 8 years ago was initially started on methimazole 20 mg/day. Later it was decreased to 10 mg/day or lower based on the thyroid function. Baseline platelet count was 140k/µl (130k - 440k/µl). Three years post initiation of methimazole, platelet count decreased compared to baseline but stayed stable between 80k - 115k/µl. Later, from 2018 - 2022 the platelet counts progressively decreased below 80k (as low as 25k/µl). In June 2022 patient was euthyroid on methimazole 10 mg/day but platelets had decreased to 51k/µl, almost half of what they were 6 months prior when the methimazole dose was averaging at 6.4 mg/day but was increased to 10 mg/day due to patient being biochemically hyperthyroid. Different doses of methimazole were attempted including 5 - 10 mg/day. Patient was able to become euthyroid only with 10 mg/day but with each methimazole dose escalation, platelet count would drop. Clinically there was no indication of bleeding. Further work up included unremarkable bone marrow aspirate, normal karyotype, normal flow cytometry, negative antiplatelet antibodies. A screen for antinuclear antibodies was negative, serum protein electrophoresis showed no monoclonal protein. Serum IgG and IgA were normal, but serum IgM was elevated to 499 mg/dl (57 – 359). Immunological studies show a decrease in C3 and C4, suggesting activation of the classical complement pathway. Alternative treatments for hyperthyroidism were discussed including radioactive iodine (RAI) and/or total thyroidectomy. At that time patient categorically refused to undergo any alternative option other than medical therapy. In late 2022 platelet count decreased to 25k/µl, but patient again refused RAI or thyroidectomy, and the decision was made to stop methimazole and start prednisone and cholestyramine to decrease free T4 and prevent further platelet decline. In 2 weeks, platelets improved to 93,000/µl. Currently, patient has agreed to proceed with RAI and will be treated soon. Of note, patient had mild degree of leukopenia with white cell count (WBC) of 4400-5000 /µL. Correlation between the WBC and the methimazole dose was not noted.Conclusion: This case shows selective significant thrombocytopenia in a patient treated with low-dose methimazole (5 - 10 mg/day). The underlying mechanism could be direct toxicity due to dose accumulation over the years in addition to immune mediated mechanisms considering the low C3 and C4 complements and serum IgM increase. Presentation: Friday, June 16, 2023