Comparison of Methimazole and Propylthiouracil in Patients with Hyperthyroidism Caused by Graves’ Disease
Abstract
CONTEXT: Although methimazole (MMI) and propylthiouracil (PTU) have long been used to treat hyperthyroidism caused by Graves' disease (GD), there is still no clear conclusion about the choice of drug or appropriate initial doses. OBJECTIVE: The aim of the study was to compare the MMI 30 mg/d treatment with the PTU 300 mg/d and MMI 15 mg/d treatment in terms of efficacy and adverse reactions. DESIGN, SETTING, AND PARTICIPANTS: Patients newly diagnosed with GD were randomly assigned to one of the three treatment regimens in a prospective study at four Japanese hospitals. MAIN OUTCOME MEASURES: Percentages of patients with normal serum free T(4) (FT4) or free T(3) (FT3) and frequency of adverse effects were measured at 4, 8, and 12 wk. RESULTS: MMI 30 mg/d normalized FT4 in more patients than PTU 300 mg/d and MMI 15 mg/d for the whole group (240 patients) at 12 wk (96.5 vs. 78.3%; P = 0.001; and 86.2%, P = 0.023, respectively). When patients were divided into two groups by initial FT4, in the group of the patients with severe hyperthyroidism (FT4, 7 ng/dl or more, 64 patients) MMI 30 mg/d normalized FT4 more effectively than PTU 300 mg/d at 8 and 12 wk and MMI 15 mg/d at 8 wk, respectively (P < 0.05). No remarkable difference between the treatments was observed in patients with initial FT4 less than 7 ng/dl. Adverse effects, especially mild hepatotoxicity, were higher with PTU and significantly lower with MMI 15 mg/d compared with MMI 30 mg/d. CONCLUSIONS: MMI 15 mg/d is suitable for mild and moderate GD, whereas MMI 30 mg/d is advisable for severe cases. PTU is not recommended for initial use.
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The MMI dose should be targeted to the degree of thyroid dysfunction because too low a dose will not restore a euthyroid state in severe disease and an excessive dose can cause iatrogenic hypothyroidism in mild disease.
“The dose of MMI should be targeted to the degree of thyroid dysfunction because too low a dose will not restore a euthyroid state in patients with severe disease (115) and an excessive dose can cause iatrogenic hypothyroidism in patients with mild disease (116).”
From 2016 American Thyroid Association Guidelines for Diagnosis and Management of Hyperthyroidism and Other Causes of Thyrotoxicosis (2016) · cites this paper as [115]
If not recognized, PTU-induced hepatotoxicity can lead to liver failure and death.
“If not recognized, it can lead to liver failure and death (115,157-159).”
From 2016 American Thyroid Association Guidelines for Diagnosis and Management of Hyperthyroidism and Other Causes of Thyrotoxicosis (2016) · cites this paper as [115]
Data in adults show only modest benefit of higher doses of MMI and only in severe thyrotoxicosis (free T4 > 7 ng/dL).
“Although there may be a tendency to use higher rather than lower doses of MMI at treatment onset, data in adults show only modest benefit of higher doses and only in severe thyrotoxicosis (free T 4 > 7 ng/dL [0.554 pmol/L]) (115).”
From 2016 American Thyroid Association Guidelines for Diagnosis and Management of Hyperthyroidism and Other Causes of Thyrotoxicosis (2016) · cites this paper as [115]
Only two studies have examined the MMI to PTU dosage ratio of 1:20 directly.
“A dosage ratio of MMI to PTU of 1:20 is recommended when changing from one drug to another (115,319,480), although only two studies have examined this dosage ratio directly (115,319).”
From 2016 American Thyroid Association Guidelines for Diagnosis and Management of Hyperthyroidism and Other Causes of Thyrotoxicosis (2016) · cites this paper as [115]
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Background
- Authors
- Nakamura, H., Noh, J. Y., Itoh, K., Fukata, S., Miyauchi, A., Hamada, N., & Working Group of the Japan Thyroid Association for the Guideline of the Treatment of Graves’ Disease
- Affiliations
- Hamamatsu University (JP)
- Ito Hospital (JP)
- Kuma Hospital (JP)
- Sumire Hospital (N.H.), Furuichi 1-20-85, Joto-ku, Osaka 536-0001, Japan
- Corresponding author
- Nakamura, Hirotoshi
- Venue
- The Journal of Clinical Endocrinology & Metabolism
- Publisher
- The Endocrine Society
- Published
- 2007-06-01
- Volume
- 92
- Issue
- 6
- Pages
- 2157-2162
- ISSN
- 0021-972X (ISSN-L)
- 1945-7197
- OpenAlex
- W2129829826
- Cited by
- 277
- References
- 16
- Citations by year
- 2026: 6 · 2025: 6 · 2024: 16 · 2023: 18 · 2022: 13 · 2021: 18 · 2020: 21 · 2019: 16 · 2018: 15 · 2017: 15 · 2016: 20 · 2015: 14 · 2014: 23 · 2013: 9 · 2012: 18
- FWCI
- 8.56
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- The Journal of Clinical Endocrinology & Metabolism (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Thyroid Disorders and Treatments
- Health Sciences › Medicine › Pathology and Forensic Medicine › Ophthalmology and Eye Disorders
- Health Sciences › Medicine › Surgery › Thyroid and Parathyroid Surgery
- Keywords
- Graves' disease, hyperthyroidism, methimazole, propylthiouracil, initial dose, hepatotoxicity, adverse drug reactions, treatment efficacy
- MeSH terms
- Adult, Female, Graves Disease, Humans, Hyperthyroidism, Male, Methimazole, Propylthiouracil, Prospective Studies, Antithyroid Agents, Thyroxine, Triiodothyronine, Treatment Outcome
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