Antithyroid drug‐related hepatotoxicity in hyperthyroidism patients: a population‐based cohort study
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Aims: The evidence of hepatotoxicity of antithyroid drugs (ATDs) is limited to case reports or spontaneous reporting. This study aimed to quantify the incidence and comparative risks of hepatotoxicity for methimazole (MMI)/carbimazole (CBM) vs. propylthiouracil (PTU) in a population‐based manner. Methods: We conducted a cohort study of hyperthyroidism patients initially receiving MMI/CBM or PTU between 1 January 2004 and 31 December 2008 using the T aiwan National Health Insurance Research Database. The examined hepatotoxicity consisted of cholestasis, non‐infectious hepatitis, acute liver failure and liver transplant, with the incidences and relative risks being quantified by Poisson exact methods and Cox proportional hazard models, respectively. Results: The study cohort comprised 71 379 ATD initiators, with a median follow‐up of 196 days. MMI/CBM vs. PTU users had a higher hepatitis incidence rate (3.17/1000 vs. 1.19/1000 person‐years) but a lower incidence of acute liver failure (0.32/1000 vs. 0.68/1000 person‐years). The relative risk analysis indicated that any use of MMI/CBM was associated with a 2.89‐fold (95% CI 1.81, 4.60) increased hepatitis risk compared with PTU, with the risk increasing to 5.08‐fold for high dose MMI/CBM (95% CI 3.15, 8.18). However, any MMI/CBM use vs. PTU was not related to an increased risk of cholestasis (adjusted hazard ratio [HR] 1.14, 95% CI 0.40, 3.72) or acute liver failure (adjusted HR 0.54, 95% CI 0.24, 1.22). Conclusions: MMI/CBM and PTU exert dissimilar incidence rates of hepatotoxicity. Compared to PTU, MMI/CBM are associated in a dose‐dependent manner with an increased risk for hepatitis while the risks are similar for acute liver failure and cholestasis.
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A diagnosis of liver failure was more common after PTU (0.048% vs. 0.026% in MMI-treated patients).
“A diagnosis of liver failure was more common after PTU (0.048% vs. 0.026% in MMI-treated patients).”
From 2016 American Thyroid Association Guidelines for Diagnosis and Management of Hyperthyroidism and Other Causes of Thyrotoxicosis (2016) · cites this paper as [134]
Among 71,379 new users of ATDs with a median follow-up of 196 days, MMI was associated with a higher rate of diagnosis of noninfectious hepatitis than PTU (0.25% vs. 0.08%), whereas cholestasis was not different (0.019% vs. 0.016%).
“Among 71,379 new users of ATDs with a median follow-up of 196 days, MMI was associated with a higher rate of a diagnosis of noninfectious hepatitis than PTU (0.25% vs. 0.08%, respectively), whereas cholestasis was not different (0.019% vs. 0.016%).”
From 2016 American Thyroid Association Guidelines for Diagnosis and Management of Hyperthyroidism and Other Causes of Thyrotoxicosis (2016) · cites this paper as [134]
A recent pharmacoepidemiologic study from Taiwan challenges the concept that MMI hepatotoxicity is usually cholestatic while PTU hepatotoxicity is most often hepatocellular.
“A recent pharmacoepidemiologic study from Taiwan challenges the concept that MMI hepatotoxicity is usually cholestatic, while PTU hepatotoxicity is most often hepatocellular (134).”
From 2016 American Thyroid Association Guidelines for Diagnosis and Management of Hyperthyroidism and Other Causes of Thyrotoxicosis (2016) · cites this paper as [134]
There have been reports of hepatocellular toxicity with MMI in adults.
“However, there have been reports of hepatocellular toxicity with MMI in adults (134).”
From 2016 American Thyroid Association Guidelines for Diagnosis and Management of Hyperthyroidism and Other Causes of Thyrotoxicosis (2016) · cites this paper as [134]
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Ross, D. S., Burch, H. B., Cooper, D. S., Greenlee, M. C., Laurberg, P., Maia, A. L., Rivkees, S. A., Samuels, M., Sosa, J. A., Stan, M. N., et al. (2016) · Thyroid® · doi:10.1089/thy.2016.0229 · Cited by 2,938 · see citing works
“A recent pharmacoepidemiologic study from Taiwan challenges the concept that MMI hepatotoxicity is usually cholestatic, while PTU hepatotoxicity is most often hepatocellular (134).”
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Antithyroid Drug Side Effects in the Population and in Pregnancy
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- Authors
- Wang, M., Lee, W., Huang, T., Chu, C., & Hsieh, C.
- Affiliations
- School of Pharmacy National Defense Medical Center Taipei Taiwan
- University of Illinois Chicago (US)
- Tri-Service General Hospital (TW)
- National Defense Medical Center (TW)
- Venue
- British Journal of Clinical Pharmacology
- Publisher
- Wiley
- Published
- 2014-08-21
- Volume
- 78
- Issue
- 3
- Pages
- 619-629
- ISSN
- 0306-5251 (ISSN-L)
- 1365-2125
- PMC
- PMC4243912
- OpenAlex
- W1497976777
- Cited by
- 114
- References
- 43
- Citations by year
- 2026: 6 · 2025: 11 · 2024: 8 · 2023: 9 · 2022: 5 · 2021: 13 · 2020: 17 · 2019: 13 · 2018: 8 · 2017: 10 · 2016: 9 · 2015: 4 · 2014: 1
- FWCI
- 9.19
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- British Journal of Clinical Pharmacology (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Taiwan National Science Council (NSC100-2320-B-016-002)
- Topics
- Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmacology › Drug-Induced Hepatotoxicity and Protection
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Thyroid Disorders and Treatments
- Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Toxicology › Pharmacovigilance and Adverse Drug Reactions
- Keywords
- antithyroid drugs, drug-induced liver injury, hyperthyroidism, methimazole, carbimazole, propylthiouracil, cholestasis, acute liver failure, liver transplantation, dose-dependent risk
- MeSH terms
- Adolescent, Adult, Aged, Carbimazole, Dose-Response Relationship, Drug, Female, Follow-Up Studies, Humans, Hyperthyroidism, Male, Methimazole, Middle Aged, Propylthiouracil, Retrospective Studies, Taiwan, Antithyroid Agents, Cohort Studies, Incidence, Proportional Hazards Models, Databases, Factual, Young Adult, Chemical and Drug Induced Liver Injury
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