Methimazole-Induced Febrile Neutropenia

Abstract

Introduction: Antithyroid drugs (ATD) are commonly used for the treatment of thyrotoxicosis, particularly for the treatment of Grave’s disease. Methimazole is the first line ATD. A major fatal adverse effect of ATDs, if unrecognized and not treated on time, is agranulocytosis, which is defined as an absolute neutrophil count of <500/μL. The incidence of ATD-induced agranulocytosis is 0.1%–0.3% (1). In this study, we report on a patient who developed granulocytopenic febrile neutropenia at 3 months after treatment with methimazole (5 mg twice a day per os (BID PO)).Case report: A 51-year-old female patient presented to the emergency department with complaints of fever, fatigue, and productive cough. Her body temperature was 38.5°C; rales were heard on the mid and basal part of the left lung. Drug history revealed methimazole use (10 mg per day over the last 2 months). The WBC count was 1020/μL, and the neutrophil count was 200/μL. The patients’ baseline WBC differential count and immune status were normal. Following inpatient antibiotic treatment and discontinuation of methimazole, the patient became afebrile within 2 days. After 2 weeks of discontinuation of methimazole, we performed CBC and observed the following: WBC, 5180/μL and neutrophil count, 3280/μL.Conclusion: Patients visiting the emergency department with symptoms of a systemic infection and known to use ATDs should be thoroughly evaluated, and the possibility of drug-induced agranulocytosis developing because of the use of these medications should be considered. It is very important for emergency physicians to recognize this rare patient population and act in a timely manner

Keywords

• Methimazole, febrile neutropenia, agranulocytosis, antithyroid drugs, fever, emergency medicine

References

1. Melmed S, Polonsky KS, P. Larsen R, Kronenberg HM. Williams textbook of endocrinology. 13th edition. ed. Hyperthyroid Disorders, ed. T.F. Da- vies, P. Laurberg, and R.S. Bahn. 2016, Philadelphia, PA: Elsevier. xviii, 1916 pages.
2. Klastersky J, de Naurois J, Rolston K, Rapoport B, Maschmeyer G, Aapro M, et al. Management of febrile neutropaenia: ESMO Clinical Practice Guidelines. Ann Oncol 2016; 27(suppl 5): p. v111-v8. [CrossRef]
3. Weetman AP. The thyroid gland and disorders of thyroid function: Oxford Textbook of Medicine. Oxford University Press; 2010: 1826-44. [CrossRef]
4. Vicente N, Cardoso L, Barros L, Carrilho F. Antithyroid Drug-Induced Agranulocytosis: State of the Art on Diagnosis and Management. Drugs R D 2017; 17: 91-6. [CrossRef]
5. Yang J, Zhong J, Xiao XH, Zhou LZ, Chen YJ, Liu JH, et al. The relation- ship between bone marrow characteristics and the clinical prognosis of antithyroid drug-induced agranulocytosis. Endocr J 2013; 60: 185-9. [CrossRef]
6. Cheung CL, Sing CW, Tang CS, Cheng VK, Pirmohamed M, Choi CH, et al. HLA-B*38:02:01 predicts carbimazole/methimazole-induced agranulo- cytosis. Clin Pharmacol Ther 2016; 99: 555-61. [CrossRef]
7. Hallberg P, Eriksson N, Ibañez L, Bondon-Guitton E, Kreutz R, Carvajal A, et al. Genetic variants associated with antithyroid drug-induced agran- ulocytosis: a genome-wide association study in a European population. Lancet Diabetes Endocrinol 2016; 4: 507-16. [CrossRef]
8. Jabr FI. Methimazole-induced severe febrile neutropenia responding to recombinant human granulocyte colony stimulating factor. South Med J 2008; 101: 665. [CrossRef]