Official reprint from UpToDate®
www.uptodate.com ©2016 UpToDate®

Amiodarone and thyroid dysfunction

Douglas S Ross, MD
Section Editor
David S Cooper, MD
Deputy Editor
Jean E Mulder, MD


Amiodarone, a class III anti-arrhythmic drug, has multiple effects on myocardial depolarization and repolarization that make it an extremely effective antiarrhythmic drug. However, amiodarone is associated with a number of side effects, including thyroid dysfunction (both hypo- and hyperthyroidism), which is due to amiodarone's high iodine content and its direct toxic effect on the thyroid. This topic will review the major effects of amiodarone on thyroid function. The clinical use and other side effects of amiodarone are reviewed elsewhere. (See "Clinical uses of amiodarone" and "Major side effects of amiodarone".)


Amiodarone contains two iodine atoms. It is estimated that amiodarone metabolism in the liver releases approximately 3 mg of inorganic iodine into the systemic circulation per 100 mg of amiodarone ingested. The average iodine content in a typical American diet is about 0.3 mg/day. Thus, 6 mg of iodine associated with a 200 mg dose of amiodarone markedly increases the daily iodine load [1,2].

Amiodarone is very lipophilic and is concentrated in adipose tissue, cardiac and skeletal muscle, and the thyroid. Elimination from the body occurs with a half-life of about 100 days [3]. Amiodarone toxicity can therefore occur well after drug withdrawal [4].

The effects of amiodarone on thyroid function can be divided into those effects that are intrinsic properties of the drug, and those effects that are due to iodine.

Intrinsic drug effects

Amiodarone inhibits outer ring 5'-monodeiodination of thyroxine (T4), thus decreasing triiodothyronine (T3) production; reverse T3 accumulates since it is not metabolized to T2 [5].


Subscribers log in here

To continue reading this article, you must log in with your personal, hospital, or group practice subscription. For more information or to purchase a personal subscription, click below on the option that best describes you:
Literature review current through: Sep 2016. | This topic last updated: May 10, 2016.
The content on the UpToDate website is not intended nor recommended as a substitute for medical advice, diagnosis, or treatment. Always seek the advice of your own physician or other qualified health care professional regarding any medical questions or conditions. The use of this website is governed by the UpToDate Terms of Use ©2016 UpToDate, Inc.
  1. Basaria S, Cooper DS. Amiodarone and the thyroid. Am J Med 2005; 118:706.
  2. Kennedy RL, Griffiths H, Gray TA. Amiodarone and the thyroid. Clin Chem 1989; 35:1882.
  3. Latini R, Tognoni G, Kates RE. Clinical pharmacokinetics of amiodarone. Clin Pharmacokinet 1984; 9:136.
  4. Martino E, Aghini-Lombardi F, Mariotti S, et al. Amiodarone: a common source of iodine-induced thyrotoxicosis. Horm Res 1987; 26:158.
  5. Rao RH, McCready VR, Spathis GS. Iodine kinetic studies during amiodarone treatment. J Clin Endocrinol Metab 1986; 62:563.
  6. Franklyn JA, Davis JR, Gammage MD, et al. Amiodarone and thyroid hormone action. Clin Endocrinol (Oxf) 1985; 22:257.
  7. van Beeren HC, Bakker O, Wiersinga WM. Structure-function relationship of the inhibition of the 3,5,3'-triiodothyronine binding to the alpha1- and beta1-thyroid hormone receptor by amiodarone analogs. Endocrinology 1996; 137:2807.
  8. Roti E, Minelli R, Gardini E, et al. Thyrotoxicosis followed by hypothyroidism in patients treated with amiodarone. A possible consequence of a destructive process in the thyroid. Arch Intern Med 1993; 153:886.
  9. Braverman LE, Ingbar SH, Vagenakis AG, et al. Enhanced susceptibility to iodide myxedema in patients with Hashimoto's disease. J Clin Endocrinol Metab 1971; 32:515.
  10. Stanbury JB, Ermans AE, Bourdoux P, et al. Iodine-induced hyperthyroidism: occurrence and epidemiology. Thyroid 1998; 8:83.
  11. Harjai KJ, Licata AA. Effects of amiodarone on thyroid function. Ann Intern Med 1997; 126:63.
  12. Trip MD, Wiersinga W, Plomp TA. Incidence, predictability, and pathogenesis of amiodarone-induced thyrotoxicosis and hypothyroidism. Am J Med 1991; 91:507.
  13. Vorperian VR, Havighurst TC, Miller S, January CT. Adverse effects of low dose amiodarone: a meta-analysis. J Am Coll Cardiol 1997; 30:791.
  14. Batcher EL, Tang XC, Singh BN, et al. Thyroid function abnormalities during amiodarone therapy for persistent atrial fibrillation. Am J Med 2007; 120:880.
  15. Martino E, Safran M, Aghini-Lombardi F, et al. Environmental iodine intake and thyroid dysfunction during chronic amiodarone therapy. Ann Intern Med 1984; 101:28.
  16. Tsadok MA, Jackevicius CA, Rahme E, et al. Amiodarone-induced thyroid dysfunction: brand-name versus generic formulations. CMAJ 2011; 183:E817.
  17. Fradkin JE, Wolff J. Iodide-induced thyrotoxicosis. Medicine (Baltimore) 1983; 62:1.
  18. Dayan CM, Daniels GH. Chronic autoimmune thyroiditis. N Engl J Med 1996; 335:99.
  19. Bagchi N, Brown TR, Urdanivia E, Sundick RS. Induction of autoimmune thyroiditis in chickens by dietary iodine. Science 1985; 230:325.
  20. Dunn JT. Guarding our nation's thyroid health. J Clin Endocrinol Metab 2002; 87:486.
  21. Nademanee K, Singh BN, Callahan B, et al. Amiodarone, thyroid hormone indexes, and altered thyroid function: long-term serial effects in patients with cardiac arrhythmias. Am J Cardiol 1986; 58:981.
  22. Martino E, Aghini-Lombardi F, Mariotti S, et al. Amiodarone iodine-induced hypothyroidism: risk factors and follow-up in 28 cases. Clin Endocrinol (Oxf) 1987; 26:227.
  23. Bartalena L, Bogazzi F, Braverman LE, Martino E. Effects of amiodarone administration during pregnancy on neonatal thyroid function and subsequent neurodevelopment. J Endocrinol Invest 2001; 24:116.
  24. Nademanee K, Piwonka RW, Singh BN, Hershman JM. Amiodarone and thyroid function. Prog Cardiovasc Dis 1989; 31:427.
  25. Bartalena L, Brogioni S, Grasso L, et al. Treatment of amiodarone-induced thyrotoxicosis, a difficult challenge: results of a prospective study. J Clin Endocrinol Metab 1996; 81:2930.
  26. Martino E, Bartalena L, Bogazzi F, Braverman LE. The effects of amiodarone on the thyroid. Endocr Rev 2001; 22:240.
  27. Lambert M, Unger J, De Nayer P, et al. Amiodarone-induced thyrotoxicosis suggestive of thyroid damage. J Endocrinol Invest 1990; 13:527.
  28. Bartalena L, Grasso L, Brogioni S, et al. Serum interleukin-6 in amiodarone-induced thyrotoxicosis. J Clin Endocrinol Metab 1994; 78:423.
  29. Brennan MD, Erickson DZ, Carney JA, Bahn RS. Nongoitrous (type I) amiodarone-associated thyrotoxicosis: evidence of follicular disruption in vitro and in vivo. Thyroid 1995; 5:177.
  30. Bouvy ML, Heerdink ER, Hoes AW, Leufkens HG. Amiodarone-induced thyroid dysfunction associated with cumulative dose. Pharmacoepidemiol Drug Saf 2002; 11:601.
  31. Bogazzi F, Bartalena L, Dell'Unto E, et al. Proportion of type 1 and type 2 amiodarone-induced thyrotoxicosis has changed over a 27-year period in Italy. Clin Endocrinol (Oxf) 2007; 67:533.
  32. Yiu KH, Jim MH, Siu CW, et al. Amiodarone-induced thyrotoxicosis is a predictor of adverse cardiovascular outcome. J Clin Endocrinol Metab 2009; 94:109.
  33. O'Sullivan AJ, Lewis M, Diamond T. Amiodarone-induced thyrotoxicosis: left ventricular dysfunction is associated with increased mortality. Eur J Endocrinol 2006; 154:533.
  34. Tomisti L, Rossi G, Bartalena L, et al. The onset time of amiodarone-induced thyrotoxicosis (AIT) depends on AIT type. Eur J Endocrinol 2014; 171:363.
  35. Daniels GH. Amiodarone-induced thyrotoxicosis. J Clin Endocrinol Metab 2001; 86:3.
  36. Martino E, Bartalena L, Mariotti S, et al. Radioactive iodine thyroid uptake in patients with amiodarone-iodine-induced thyroid dysfunction. Acta Endocrinol (Copenh) 1988; 119:167.
  37. Eaton SE, Euinton HA, Newman CM, et al. Clinical experience of amiodarone-induced thyrotoxicosis over a 3-year period: role of colour-flow Doppler sonography. Clin Endocrinol (Oxf) 2002; 56:33.
  38. Bogazzi F, Martino E, Dell'Unto E, et al. Thyroid color flow doppler sonography and radioiodine uptake in 55 consecutive patients with amiodarone-induced thyrotoxicosis. J Endocrinol Invest 2003; 26:635.
  39. Piga M, Cocco MC, Serra A, et al. The usefulness of 99mTc-sestaMIBI thyroid scan in the differential diagnosis and management of amiodarone-induced thyrotoxicosis. Eur J Endocrinol 2008; 159:423.
  40. Bogazzi F, Bartalena L, Tomisti L, et al. Continuation of amiodarone delays restoration of euthyroidism in patients with type 2 amiodarone-induced thyrotoxicosis treated with prednisone: a pilot study. J Clin Endocrinol Metab 2011; 96:3374.
  41. Eskes SA, Endert E, Fliers E, et al. Treatment of amiodarone-induced thyrotoxicosis type 2: a randomized clinical trial. J Clin Endocrinol Metab 2012; 97:499.
  42. Osman F, Franklyn JA, Sheppard MC, Gammage MD. Successful treatment of amiodarone-induced thyrotoxicosis. Circulation 2002; 105:1275.
  43. Bogazzi F, Bartalena L, Martino E. Approach to the patient with amiodarone-induced thyrotoxicosis. J Clin Endocrinol Metab 2010; 95:2529.
  44. Martino E, Aghini-Lombardi F, Mariotti S, et al. Treatment of amiodarone associated thyrotoxicosis by simultaneous administration of potassium perchlorate and methimazole. J Endocrinol Invest 1986; 9:201.
  45. Dickstein G, Shechner C, Adawi F, et al. Lithium treatment in amiodarone-induced thyrotoxicosis. Am J Med 1997; 102:454.
  46. Maqdasy S, Batisse-Lignier M, Auclair C, et al. Amiodarone-Induced Thyrotoxicosis Recurrence After Amiodarone Reintroduction. Am J Cardiol 2016; 117:1112.
  47. Hermida JS, Jarry G, Tcheng E, et al. Radioiodine ablation of the thyroid to allow the reintroduction of amiodarone treatment in patients with a prior history of amiodarone-induced thyrotoxicosis. Am J Med 2004; 116:345.
  48. Bogazzi F, Miccoli P, Berti P, et al. Preparation with iopanoic acid rapidly controls thyrotoxicosis in patients with amiodarone-induced thyrotoxicosis before thyroidectomy. Surgery 2002; 132:1114.
  49. Houghton SG, Farley DR, Brennan MD, et al. Surgical management of amiodarone-associated thyrotoxicosis: Mayo Clinic experience. World J Surg 2004; 28:1083.
  50. Tomisti L, Materazzi G, Bartalena L, et al. Total thyroidectomy in patients with amiodarone-induced thyrotoxicosis and severe left ventricular systolic dysfunction. J Clin Endocrinol Metab 2012; 97:3515.
  51. Bogazzi F, Tomisti L, Rossi G, 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 2009; 94:3757.
  52. Uzan L, Guignat L, Meune C, et al. Continuation of amiodarone therapy despite type II amiodarone-induced thyrotoxicosis. Drug Saf 2006; 29:231.
  53. Bogazzi F, Bartalena L, Tomisti L, et al. Glucocorticoid response in amiodarone-induced thyrotoxicosis resulting from destructive thyroiditis is predicted by thyroid volume and serum free thyroid hormone concentrations. J Clin Endocrinol Metab 2007; 92:556.
  54. Bogazzi F, Bartalena L, Cosci C, et al. Treatment of type II amiodarone-induced thyrotoxicosis by either iopanoic acid or glucocorticoids: a prospective, randomized study. J Clin Endocrinol Metab 2003; 88:1999.
  55. Yagishita A, Hachiya H, Kawabata M, et al. Amiodarone-induced thyrotoxicosis late after amiodarone withdrawal. Circ J 2013; 77:2898.
  56. Kurnik D, Loebstein R, Farfel Z, et al. Complex drug-drug-disease interactions between amiodarone, warfarin, and the thyroid gland. Medicine (Baltimore) 2004; 83:107.