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A Case of Methimazole-Induced Acute Pancreatitis With an HLA Allele Causing Antithyroid Drug-Induced Agranulocytosis
Yusuke Yoshimura1, Keita Tatsushima1, Yukiko Goshima1
1Department of Endocrinology and Metabolism, Toranomon Hospital, Minato-ku, Tokyo 105-8470, Japan.
Abstract:
Among the side effects of methimazole (MMI) for the treatment of Graves' disease, MMI-induced acute pancreatitis (MIP) is a rare adverse reaction, with only 7 cases being reported to date. However, 2 large-scale population-based studies recently revealed that the risk of MIP was significantly higher, ranging from 0.02% to 0.56%. Although MIP is common in middle-aged and elderly Asian women, its pathogenesis remains largely unknown. We herein present a case of a 72-year-old Japanese woman with Graves' disease who developed MIP 12 days after the initiation of MMI. The MMI was discontinued, the patient was switched to propylthiouracil (PTU) therapy, and pancreatitis gradually resolved. Serological human leukocyte antigen (HLA) typing identified HLA-DRB1*08:03:02. This HLA allele was previously detected in a patient with MIP and is one of the major risk factors for agranulocytosis induced by antithyroid drugs, including PTU as well as MMI. In cases of MIP, PTU is being considered as an alternative to MMI; however, its safety needs further investigation and patients require close monitoring after the switch to PTU. Further studies are warranted, particularly on the relationship between MIP and the presence of HLA alleles causing antithyroid drug-induced agranulocytosis.
Insights
Methimazole can cause rare acute pancreatitis in Graves' disease patients. A specific human leukocyte antigen (HLA) allele, HLA-DRB1*08:03:02, may increase this risk, necessitating careful monitoring when switching treatments.
Area of Science:
- Endocrinology
- Pharmacology
- Immunogenetics
Background:
- Graves' disease is commonly treated with methimazole (MMI).
- MMI-induced acute pancreatitis (MIP) is a rare but significant adverse reaction.
- The pathogenesis of MIP, particularly in relation to genetic factors, is not well understood.
Observation:
- A 72-year-old Japanese woman with Graves' disease developed acute pancreatitis 12 days after starting MMI.
- Pancreatitis resolved after discontinuing MMI and switching to propylthiouracil (PTU).
- Genetic analysis revealed the patient possessed the HLA-DRB1*08:03:02 allele.
Findings:
- The identified HLA-DRB1*08:03:02 allele has been previously associated with MIP.
- This HLA allele is also a known risk factor for agranulocytosis induced by antithyroid drugs like MMI and PTU.
- The case suggests a potential genetic predisposition to MIP linked to specific HLA alleles.
Implications:
- Propylthiouracil (PTU) may be considered as an alternative to MMI for patients with Graves' disease who develop MIP.
- The safety of switching to PTU in patients with MIP requires further investigation and close monitoring.
- Further research into the association between MIP, HLA alleles, and antithyroid drug-induced agranulocytosis is warranted.
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