Abstract
Amiodarone is a benzofuran derivative approved for the treatment of cardiac arrhythmias. Traditionally classified as a class III antiarrhythmic agent, amiodarone possesses electrophysiologic properties of all four Vaughan–Williams classes. This drug, however, has high iodine content, and this feature plus the intrinsic effects on the body make amiodarone especially toxic to the thyroid gland. Treatment can result in a range of effects from mild derangements in thyroid function to overt hypothyroidism or thyrotoxicosis. The diagnosis and treatment of amiodarone-induced hypothyroidism is usually straightforward, whereas that of amiodarone-induced thyrotoxicosis and the ability to distinguish between the type 1 and type 2 forms of the disease are much more challenging. Dronedarone was approved in 2009 for the treatment of patients with atrial fibrillation. As amiodarone, dronedarone is a benzofuran derivative with similar electrophysiologic properties. In contrast to amiodarone, however, dronedarone is structurally devoid of iodine and has a notably shorter half-life. In studies reported before FDA approval, dronedarone proved to be associated with significantly fewer adverse effects than amiodarone, making it a more attractive choice for patients with atrial fibrillation or flutter, who are at risk of developing amiodarone-induced thyroid dysfunction.
Key Points
-
Amiodarone, an iodine-rich benzofuran derivative, is approved for the treatment of ventricular arrhythmias, but is often used in the treatment of atrial fibrillation
-
Amiodarone and its active metabolite desethylamiodarone have multiple electrophysiologic effects
-
Untoward effects associated with amiodarone use, including effects on the pulmonary, gastrointestinal, ophthalmologic, neurologic, dermatologic and thyroid systems, are prevalent and have resulted in decreased use of the drug
-
Amiodarone-induced thyroid dysfunction, including hypothyroidism and hyperthyroidism, may be due to iodine effects or to intrinsic drug effects
-
Treatment of amiodarone-induced thyrotoxicosis (AIT) varies depending on the type of AIT and does not necessarily include discontinuation of amiodarone treatment
-
Dronedarone, a benzofuran derivative that does not contain iodine, has been approved by the FDA for the treatment of atrial fibrillation and demonstrates less thyroid-related toxic effects than amiodarone
This is a preview of subscription content, access via your institution
Relevant articles
Open Access articles citing this article.
-
Critically ill severe hypothyroidism: a retrospective multicenter cohort study
Annals of Intensive Care Open Access 09 March 2023
Access options
Subscribe to this journal
Receive 12 print issues and online access
$209.00 per year
only $17.42 per issue
Rent or buy this article
Prices vary by article type
from$1.95
to$39.95
Prices may be subject to local taxes which are calculated during checkout



References
Fuster, V. et al. ACC/AHA/ESC 2006 guidelines for the management of patients with atrial fibrillation. Circulation 114, 700–752 (2006).
Han, T. S., Williams, G. R. & Vanderpump, M. P. J. Benzofuran derivatives and the thyroid. Clin. Endocrinol. (Oxf.) 70, 2–13 (2009).
Basaria, S. & Cooper, D. S. Amiodarone and the thyroid. Am. J. Med. 118, 706–714 (2005).
Nattel, S., Talajic, M., Fermini, B. & Roy, D. Amiodarone: pharmacology, clinical actions and relationships between them. J. Cardiovasc. Electrophysiol. 3, 266–280 (1992).
Singh, B. N. Amiodarone as paradigm for developing new drugs for atrial fibrillation. J. Cardiovasc. Pharmacol. 52, 300–305 (2008).
Bogazzi, F., Bartalena, L., Gaasperi, M., Braverman, L. E. & Martino, E. The various effects of amiodarone on thyroid function. Thyroid 11, 511–519 (2001).
Martino, E., Bartalena, L., Bogazzi, F. & Braverman, L. E. The effects of amiodarone on the thyroid. Endocr. Rev. 22, 240–254 (2001).
Miller, J. M. & Zipes, D. P. in Braunwald's Heart Disease: A Textbook of Cardiovascular Medicine 8th edn Ch. 33 (eds Libby, P., Zipes, D. P., Mann, D. P. & Bonow, R. O.) 779–830 (Elsevier Science, Philadelphia, 2007).
Zimetbaum, P. Amiodarone for atrial fibrillation. N. Engl. J. Med. 356, 935–941 (2007).
Vassallo, P. & Trohman, R. Prescribing amiodarone: an evidence-based review of clinical indications. JAMA 298, 1312–1322 (2007).
Levey, G. S. & Klein, I. in Stein's Textbook of Internal Medicine 2nd edn Ch. 297 (ed. Stein, J. H.) 1797–1817 (Little, Brown and Company, Boston, 1994).
Kopp, P. in The Thyroid: A Fundamental and Clinical Text, 9th edn Ch. 4B (eds Braverman, L. E. & Utiger, R. D.) 52–76 (Lippincott Williams & Wilkins, Philadelphia, 2005).
Braverman, L. E. & Ingbar, S. H. Changes in thyroidal function during adaptation to large doses of iodide. J. Clin. Invest. 42, 1216–1231 (1963).
Eng, P. H. et al. Escape from the acute Wolff–Chaikoff effect is associated with a decrease in thyroid sodium/iodide symporter messenger ribonucleic acid and protein. Endocrinology 140, 3404–3410 (1999).
Daniels, G. H. Amiodarone-induced thyrotoxicosis. J. Clin. Endocrinol. Metab. 86, 3–8 (2001).
Koenig, R. J. Regulation of type 1 iodothyronine deiodinase in health and disease. Thyroid 15, 835–840 (2005).
Newman, C. M., Price, A., Davies, D. W., Gray, T. A. & Weetman, A. P. Amiodarone and the thyroid: a practical guide to the management of thyroid dysfunction induced by amiodarone therapy. Heart 79, 121–127 (1998).
Bogazzi, F. et al. Desethylamiodarone antagonizes the effect of thyroid hormone at the molecular level. Eur. J. Endocrinol. 145, 59–64 (2001).
Chiovato, L. et al. Studies on the in vitro cytotoxic effect of amiodarone. Endocrinology 134, 2277–2282 (1994).
Advisory Committee Meeting of the Cardiovascular and Renal Drug Division of the US Food and Drug Administration. Multaq (Dronedarone) Briefing Document http://www.fda.gov/downloads/AdvisoryCommittees/CommitteesMeetingMaterials/Drugs/CardiovascularandRenalDrugsAdvisoryCommittee/UCM134981.pdf (2009).
Trip, M. D., Wiersinga, W. & Plomp, T. A. Incidence, predictability, and pathogenesis of amiodarone-induced thyrotoxicosis and hypothyroidism. Am. J. Med. 91, 507–511 (1991).
Martino, E. et al. Environmental iodine intake and thyroid dysfunction during chronic amiodarone therapy. Ann. Intern. Med. 101, 28–34 (1984).
Martino, E. et al. Amiodarone iodine-induced hypothyroidism: risk factors and follow-up in 28 cases. Clin. Endocrinol. (Oxf.) 26, 227–237 (1987).
Tedelind, S. et al. Amiodarone inhibits thyroidal iodide transport in vitro by a cyclic adenosine 5′-monophosphate- and iodine-independent mechanism. Endocrinology 147, 2936–2943 (2006).
Schenck, J. B., Rizvi, A. A. & Lin, T. Severe primary hypothyroidism manifesting with torsades de pointes. Am. J. Med. Sci. 331, 154–156 (2006).
Luciani, R., Falcone, C., Principe, F., Punzo, G. & Menè, P. Acute renal failure due to amiodarone-induced hypothyroidism. Clin. Nephrol. 72, 79–80 (2009).
Klein, I. & Danzi, S. Thyroid disease and the heart. Circulation 116, 1725–1735 (2007).
Surks, M. I. et al. Subclinical thyroid disease: scientific review and guidelines for diagnosis and management. JAMA 291, 228–238 (2004).
Klein, I. & Ojamaa, K. Thyroid hormone and the cardiovascular system. N. Engl. J. Med. 344, 501–509 (2001).
Polikar, R. et al. Effect of oral triiodothyronine during amiodarone treatment for ventricular premature complexes. Am. J. Cardiol. 58, 987–991 (1986).
Stanbury, J. B. et al. Iodine-induced hyperthyroidism: occurrence and epidemiology. Thyroid 8, 83–100 (1998).
Harjai, K. J. & Licata, A. A. Effects of amiodarone on thyroid function. Ann. Intern. Med. 126, 163–173 (1997).
Sidhu, J. & Jenkins, D. Men are at increased risk of amiodarone-associated thyrotoxicosis in the UK. QJM 96, 949–950 (2003).
Bogazzi, F. et al. Proportion of type 1 and type 2 amiodarone-induced thyrotoxicosis has changed over a 27-year period in Italy. Clin. Endocrinol. (Oxf.) 67, 533–537 (2007).
Kurnik, D. et al. Complex drug-drug-disease interactions between amiodarone, warfarin, and the thyroid gland. Medicine (Baltimore) 83, 107–113 (2004).
Amico, J. A., Richardson, V., Alpert, B. & Klein, I. Clinical and chemical assessment of thyroid function during therapy with amiodarone. Arch. Intern. Med. 144, 487–490 (1984).
Bartalena, L. et al. Interleukin-6: a marker of thyroid destructive processes? J. Clin. Endocrinol. Metab. 79, 1424–1427 (1994).
Eaton, S. E., Euinton, H. A., Newman, C. M., Weetman, A. P. & Bennet, W. M. Clinical experience of amiodarone-induced thyrotoxicosis over a 3-year period: role of colour-flow Doppler sonography. Clin. Endocrinol. (Oxf.) 56, 33–38 (2002).
Tanda, M. L., Bogazzi, F., Martino, E. & Bartalena, L. Amiodarone-induced thyrotoxicosis: something new to refine the initial diagnosis? Eur. J. Endocrinol. 159, 359–361 (2008).
Bogazzi, F. et al. Color flow Doppler sonography rapidly differentiates type I and type II amiodarone-induced thyrotoxicosis. Thyroid 7, 541–545 (1997).
Martino, E. et al. Twenty-four hour radioactive iodine uptake in 35 patients with amiodarone associated thyrotoxicosis. J. Nucl. Med. 26, 1402–1407 (1985).
Yiu, K. H. et al. Amiodarone-induced thyrotoxicosis is a predictor of adverse cardiovascular outcome. J. Clin. Endocrinol. Metab. 94, 109–114 (2009).
Bartalena, L., Bogazzi, F. & Martino, E. Amiodarone-induced thyrotoxicosis: a difficult diagnostic and therapeutic challenge. Clin. Endocrinol. (Oxf.) 56, 23–24 (2002).
Bartalena, L. et al. Treatment of amiodarone-induced thyrotoxicosis, a difficult challenge: results of a prospective study. J. Clin. Endocrinol. Metab. 81, 2930–2933 (1996).
Osman, F., Franklyn, J. A., Sheppard, M. C. & Gammage, M. D. Successful treatment of amiodarone-induced thyrotoxicosis. Circulation 105, 1275–1277 (2002).
Bogazzi, F. et al. Treatment of type II amiodarone-induced thyrotoxicosis by either iopanoic acid or glucocorticoids: a prospective, randomized study. J. Clin. Endocrinol. Metab. 88, 1999–2002 (2003).
Bogazzi, F. et al. Glucocorticoids are preferable to thionamides as first-line treatment for amiodarone-induced thyrotoxicosis due to destructive thyroiditis: a matched retrospective cohort study. J. Clin. Endocrinol. Metab. 10.1210/jc.2009–0940.
Farwell, A. P., Abend, S. L., Huang, S. K., Patwardhan, N. A. & Braverman, L. E. Thyroidectomy for amiodarone-induced thyrotoxicosis. JAMA 263, 1526–1528 (1990).
Gough, J. & Gough, I. R. Total thyroidectomy for amiodarone-induced thyrotoxicosis in patients with severe cardiac disease. World J. Surg. 30, 1957–1961 (2006).
Wolff, J. Perchlorate and the thyroid gland. Pharm. Rev. 50, 89–105 (1998).
Martino, E., Aghini-Lombardi, F., Mariotti, S., Lenziardi, M. & Baschieri, L. Treatment of amiodarone associated thyrotoxicosis by simultaneous administration of potassium perchlorate and methimazole. J. Endocrinol. Invest. 9, 201–207 (1986).
Bartalena, L. et al. Diagnosis and management of amiodarone-induced thyrotoxicosis in Europe: results of an international survey among members of the European Thyroid Association. Clin. Endocrinol. (Oxf.) 61, 494–502 (2004).
Uzan, L. et al. Continuation of amiodarone therapy despite type II amiodarone-induced thyrotoxicosis. Drug Saf. 29, 231–236 (2006).
Hohnloser, S. H. et al. Effect of dronedarone on cardiovascular events in atrial fibrillation. N. Engl. J. Med. 360, 668–678 (2009).
Singh, B. N. et al. Dronedarone for maintenance of sinus rhythm in atrial fibrillation or flutter. N. Engl. J. Med. 357, 987–999 (2007).
Davy, J. M. et al. Dronedarone for the control of ventricular rate in permanent atrial fibrillation: the Efficacy and safety of dRonedArone for The cOntrol of ventricular rate during atrial fibrillation (ERATO) study. Am. Heart J. 156, 527.e1–527.e9 (2008).
Kathofer, S., Thomas, D. & Karle, C. A. The novel antiarrhythmic drug dronedarone: comparison with amiodarone. Cardiovasc. Drug Rev. 23, 217–230 (2005).
Touboul, P. et al. Dronedarone for prevention of atrial fibrillation: a dose-ranging study. Eur. Heart J. 24, 1481–1487 (2003).
Hohnloser, S. H. New pharmacological options for patients with atrial fibrillation: the ATHENA trial. Rev. Esp. Cardiol. 62, 479–481 (2009).
Tschuppert, Y. et al. Effect of dronedarone on renal function in healthy subjects. Br. J. Clin. Pharmacol. 64, 785–791 (2007).
Author information
Authors and Affiliations
Corresponding author
Ethics declarations
Competing interests
The authors, the Journal Editor V. Heath and the CME questions author Désirée Lie declare no competing interests.
Rights and permissions
About this article
Cite this article
Cohen-Lehman, J., Dahl, P., Danzi, S. et al. Effects of amiodarone therapy on thyroid function. Nat Rev Endocrinol 6, 34–41 (2010). https://doi.org/10.1038/nrendo.2009.225
Published:
Issue Date:
DOI: https://doi.org/10.1038/nrendo.2009.225
This article is cited by
-
Critically ill severe hypothyroidism: a retrospective multicenter cohort study
Annals of Intensive Care (2023)
-
SchilddrĂĽse und Herz
Der Internist (2018)
-
Arrhythmia and thyroid dysfunction
Herz (2015)