Treatment of Amiodarone-Induced Thyrotoxicosis Type 2: A Randomized Clinical Trial
Abstract
CONTEXT: Amiodarone-induced thyrotoxicosis (AIT) type 2 is self-limiting in nature, but most physicians are reluctant to continue amiodarone. When prednisone fails to restore euthyroidism, possibly due to mixed cases of AIT type 1 and 2, perchlorate (ClO(4)) might be useful because ClO(4) reduces the cytotoxic effect of amiodarone on thyrocytes. OBJECTIVES: Our objectives were to demonstrate the feasibility of continuation of amiodarone in AIT type 2 and to evaluate the usefulness of ClO(4) (given alone or in combination with prednisone) in AIT type 2. DESIGN AND SETTING: A randomized multicenter study was conducted in 10 Dutch hospitals. METHODS: Patients with AIT type 2 were randomized to receive prednisone 30 mg/d (group A, n = 12), sodium perchlorate 500 mg twice daily (group B, n = 14), or prednisone plus perchlorate (group C, n = 10); all patients continued amiodarone and were also treated with methimazole 30 mg/d. Follow-up was 2 yr. MAIN OUTCOME MEASURES: Treatment efficacy (defined as TSH values ≥ 0.4 mU/liter under continuation of amiodarone) and recurrent thyrotoxicosis were evaluated. RESULTS: Initial therapy was efficacious in 100, 71, and 100% of groups A, B, and C, respectively (P = 0.03). The 29% failures in group B became euthyroid after addition of prednisone. Neither the time to reach TSH of 0.4 mU/liter or higher [8 wk (4-20), 14 wk (4-32), and 12 wk (4-28) in groups A, B, and C respectively] nor the time to reach free T(4) of 25 pmol/liter or below [4 wk (4-20), 12 wk (4-20), and 8 wk (4-20) in groups A, B, and C) were significantly different between groups (values as median with range). Recurrent thyrotoxicosis occurred in 8.3%. CONCLUSION: Euthyroidism was reached despite continuation of amiodarone in all patients. Prednisone remains the preferred treatment modality of AIT type 2, because perchlorate given alone or in combination with prednisone had no better outcomes.
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Type 2 AIT typically responds to treatment even if amiodarone therapy is continued, but continuation may lead to a more prolonged time to recovery and a higher rate of future recurrences of AIT.
“In addition, type 2 AIT typically responds to treatment even if amiodarone therapy is continued (585-587), but continuation may lead to a more prolonged time to recovery and a higher rate of future recurrences of AIT (588).”
From 2016 American Thyroid Association Guidelines for Diagnosis and Management of Hyperthyroidism and Other Causes of Thyrotoxicosis (2016) · cites this paper as [586]
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- Authors
- Eskes, S. A., Endert, E., Fliers, E., Geskus, R. B., Dullaart, R. P. F., Links, T. P., & Wiersinga, W. M.
- Affiliations
- Amsterdam UMC Location University of Amsterdam (NL)
- University of Amsterdam (NL)
- University Medical Center Groningen (NL)
- Corresponding author
- Eskes, Silvia A.
- Venue
- The Journal of Clinical Endocrinology & Metabolism
- Publisher
- The Endocrine Society
- Published
- 2012-02
- Volume
- 97
- Issue
- 2
- Pages
- 499-506
- ISSN
- 0021-972X (ISSN-L)
- 1945-7197
- OpenAlex
- W2054823284
- Cited by
- 78
- References
- 23
- Citations by year
- 2026: 7 · 2025: 1 · 2024: 4 · 2023: 4 · 2022: 6 · 2021: 7 · 2020: 7 · 2019: 5 · 2018: 6 · 2017: 4 · 2016: 6 · 2014: 7 · 2013: 6 · 2012: 7
- FWCI
- 5.25
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- The Journal of Clinical Endocrinology & Metabolism (publishedVersion)
- PubMed (publishedVersion)
- Pure Amsterdam UMC (publishedVersion)
- University of Groningen research database (University of Groningen / Centre for Information Technology) (publishedVersion)
- Data Archiving and Networked Services (DANS) (submittedVersion)
- University of Groningen research database (University of Groningen / Centre for Information Technology) (submittedVersion)
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Thyroid Disorders and Treatments
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Adrenal Hormones and Disorders
- Health Sciences › Medicine › Pathology and Forensic Medicine › Ophthalmology and Eye Disorders
- Keywords
- amiodarone-induced thyrotoxicosis, sodium perchlorate, prednisone, methimazole, thyroid-stimulating hormone, free thyroxine, antithyroid drug therapy, drug-induced thyroid dysfunction, antithyroid drug withdrawal
- MeSH terms
- Adult, Aged, Amiodarone, Anti-Arrhythmia Agents, Feasibility Studies, Female, Follow-Up Studies, Humans, Male, Middle Aged, Perchlorates, Recurrence, Antithyroid Agents, Thyroid Function Tests, Thyrotoxicosis, Treatment Outcome, Endocrine Disruptors
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