Hepatotoxicity and cutaneous reactions after antithyroid drug administration
Abstract
Summary: Objective: Use of the antithyroid drugs (ATD s) thiamazole (MMI) and propylthiouracil (PTU) is associated with a high frequency of side effects. When patients experience side effects with one (the 1st) ATD, it is usually discontinued and another is administered (the 2nd ATD). We investigated side effects associated with the 1st and 2nd ATD s. Design and Patients: Four hundred forty‐nine patients with untreated Graves' disease (GD) were randomly assigned to three groups according to ATD type and/or dosage: 15 mg/day MMI, 30 mg/day MMI and 300 mg/day PTU. The type, frequency and onset of side effects were assessed. We also studied the side effects associated with the 2nd ATD after cessation of the 1st ATD. Measurements: Cutaneous reactions, liver dysfunction and other side effects were examined every 2 weeks after starting ATD administration. Results: The overall frequency of side effects in patients taking 15 mg/day MMI was low. The frequencies of cutaneous reactions in patients taking 30 mg/day MMI and hepatotoxicity in those taking 300 mg/day PTU were high. Hepatotoxicity developed later than cutaneous reactions with PTU. Hepatotoxicity developed earlier in the 30 mg/day MMI group than in the other two groups. The frequency of side effects did not differ between the 2nd and 1st ATD s. Hepatotoxicity occurred at a higher frequency in patients who were switched from MMI to PTU because of hepatotoxicity of the former. Conclusion: Attention to the onset times of side effects and cross‐reactivity of ATD s can lead to safer treatment of GD.
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Cutaneous reactions appeared after a median of 18-22 days of treatment, significantly earlier than transaminase elevations at a median of 28 days.
“Cutaneous reactions appeared after a median of 18-22 days of treatment, significantly earlier than transaminase elevations (median 28 days).”
From 2016 American Thyroid Association Guidelines for Diagnosis and Management of Hyperthyroidism and Other Causes of Thyrotoxicosis (2016) · cites this paper as [123]
The percentage of patients discontinuing ATD therapy was 17% in the low-dose MMI group, 29% in the high-dose MMI group, and 34% in the PTU group.
“The percentage of patients discontinuing ATD therapy was 17% in the low-dose MMI group, 29% in the high-dose MMI group, and 34% in the PTU group (123).”
From 2016 American Thyroid Association Guidelines for Diagnosis and Management of Hyperthyroidism and Other Causes of Thyrotoxicosis (2016) · cites this paper as [123]
In a separate study of 449 Graves' disease patients receiving MMI or PTU, 24% developed a cutaneous reaction, 3.8% developed transaminase elevations more than 3-fold above normal, and 0.7% developed agranulocytosis with absolute neutrophil count less than 500.
“In a separate study of 449 GD patients receiving MMI or PTU, 24% developed a cutaneous reaction, 3.8% developed transaminase elevations more than 3-fold above normal, and 0.7% developed agranulocytosis (absolute neutrophil count <500) (123).”
From 2016 American Thyroid Association Guidelines for Diagnosis and Management of Hyperthyroidism and Other Causes of Thyrotoxicosis (2016) · cites this paper as [123]
Hepatotoxicity was more common with PTU.
“Hepatotoxicity was more common with PTU.”
From 2016 American Thyroid Association Guidelines for Diagnosis and Management of Hyperthyroidism and Other Causes of Thyrotoxicosis (2016) · cites this paper as [123]
Cutaneous reactions were more common with PTU or higher-dose MMI (30 mg/d) compared with lower-dose MMI (15 mg/d).
“Cutaneous reactions were more common with PTU or higher dose MMI (30 mg/d) compared with lower dose MMI (15 mg/d).”
From 2016 American Thyroid Association Guidelines for Diagnosis and Management of Hyperthyroidism and Other Causes of Thyrotoxicosis (2016) · cites this paper as [123]
In 71 patients with an adverse event from either MMI or PTU who switched to the other ATD, 34% of patients switched to PTU and 30% of patients switched to MMI developed side effects, generally the same type as occurred on the original ATD, while the remaining patients tolerated the second ATD without complications.
“Thirty-four percent of patients switched to PTU and 30% of patients switched to MMI developed side effects, generally the same type as occurred on the original ATD, while the remaining patients tolerated the second ATD without complications (123).”
From 2016 American Thyroid Association Guidelines for Diagnosis and Management of Hyperthyroidism and Other Causes of Thyrotoxicosis (2016) · cites this paper as [123]
Switching from one ATD to the other is safe in the case of minor side effects, although patients may develop similar side effects with the second ATD.
“A recent study provided evidence that switching from one ATD to the other is safe in the case of minor side effects, although patients may develop similar side effects with the second ATD (123).”
From 2016 American Thyroid Association Guidelines for Diagnosis and Management of Hyperthyroidism and Other Causes of Thyrotoxicosis (2016) · cites this paper as [123]
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- Authors
- Otsuka, F., Noh, J. Y., Chino, T., Shimizu, T., Mukasa, K., Ito, K., Ito, K., & Taniyama, M.
- Affiliations
- Ito Hospital (JP)
- SHOWA Medical University Fujigaoka Hospital (JP)
- Corresponding author
- Otsuka, Fumiko
- Venue
- Clinical Endocrinology
- Publisher
- Wiley
- Published
- 2012-07-10
- Volume
- 77
- Issue
- 2
- Pages
- 310-315
- ISSN
- 0300-0664 (ISSN-L)
- 1365-2265
- OpenAlex
- W1990677808
- Cited by
- 63
- References
- 15
- Citations by year
- 2026: 5 · 2025: 5 · 2024: 4 · 2023: 4 · 2022: 4 · 2021: 7 · 2020: 4 · 2019: 5 · 2018: 6 · 2017: 4 · 2016: 4 · 2015: 3 · 2014: 5 · 2013: 2 · 2012: 1
- FWCI
- 2.82
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Clinical Endocrinology (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Thyroid Disorders and Treatments
- Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmacology › Drug-Induced Hepatotoxicity and Protection
- Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Toxicology › Pharmacovigilance and Adverse Drug Reactions
- Keywords
- antithyroid drugs, hepatotoxicity, skin reactions, Graves' disease, methimazole, propylthiouracil, adverse drug reactions, drug switching, drug dosing, liver dysfunction, drug cross-reactivity
- MeSH terms
- Adolescent, Adult, Aged, Drug Administration Schedule, Female, Graves Disease, Humans, Liver, Male, Methimazole, Middle Aged, Propylthiouracil, Skin, Antithyroid Agents, Young Adult
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