Treatment with amiodarone is associated with changes in thyroid function tests, but also with thyroid dysfunction (amiodarone-induced hypothyroidism, AIH, and amiodarone-induced thyrotoxicosis, AIT). Both AIH and AIT may develop in apparently normal thyroid glands or in the presence of underlying thyroid abnormalities. AIH does not require amiodarone withdrawal, and is treated with levothyroxine replacement if overt, whereas subclinical forms may be followed without treatment. Two main types of AIT are recognized: type 1 AIT (AIT 1), a form of iodine-induced hyperthyroidism occurring in nodular goitres or latent Graves disease, and type 2 AIT (AIT 2), resulting from destructive thyroiditis in a normal thyroid gland. Mixed/indefinite forms exist due to both pathogenic mechanisms. AIT 1 is best treated with thionamides that may be combined for a few weeks with sodium perchlorate to make the thyroid gland more sensitive to thionamides. AIT 2 is treated with oral glucocorticoids. Once euthyroidism has been restored, AIT 2 patients are followed up without treatment, whereas AIT 1 patients should be treated with thyroidectomy or radioiodine. Mixed/indefinite forms of AIT are treated with thionamides. Oral glucocorticoids can be added from the beginning if a precise diagnosis is uncertain, or after a few weeks if response to thionamides alone is poor. The decision to continue or to stop amiodarone in AIT should be individualized in relation to cardiovascular risk stratification and taken jointly by specialist cardiologists and endocrinologists. In the presence of rapidly deteriorating cardiac conditions, emergency thyroidectomy may be required for all forms of AIT.

1.
Bogazzi F, Bartalena L, Martino E: Approach to the patient with amiodarone-induced thyrotoxicosis. J Clin Endocrinol Metab 2010; 95: 2529–2535.
2.
Martino E, Bartalena L, Bogazzi F, Braverman LE: The effects of amiodarone on the thyroid. Endocr Rev 2001; 22: 240–254.
3.
Tanda ML, Piantanida E, Lai A, Liparulo L, Sassi L, Bogazzi F, Wiersinga WM, Braverman LE, Braverman LE, Martino E, Bartalena L: Diagnosis and management of amiodarone-induced thyrotoxicosis: similarities and differences between North American and European thyroidologists. Clin Endocrinol (Oxf) 2008; 69: 812–818.
4.
Raghavan RP, Taylor PN, Bhake R, Vaidya B, Martino E, Bartalena L, Dayan CM, Bradley K: Amiodarone-induced thyrotoxicosis: an overview of UK management. Clin Endocrinol (Oxf) 2012; 77: 936–937.
5.
Ahmed S, Van Gelder IC, Wiesfeld ACP, Van Veldhuisen DJ, Links TP: Determinants and outcome of amiodarone-associated thyroid dysfunction. Clin Endocrinol (Oxf) 2011; 75: 388–394.
6.
Trip MD, Wiersinga W, Plomp TA: Incidence, predictability, and pathogenesis of amiodarone-induced thyrotoxicosis and hypothyroidism. Am J Med 1991; 91: 507–511.
7.
Swiglo BA, Murad MH, Schunemann HJ, Kunz R, Vigersky RA, Guyatt GH, Montori VM: A case for clarity, consistency and helpfulness: State-of-the-art clinical practice guidelines in endocrinology using the grading of recommendations, assessment, development, and evaluation system. J Clin Endocrinol Metab 2008; 93: 666–673.
8.
Lambert MJ, Burger AG, Galeazzi RL, Engler D: Are selective increases in serum thyroxine (T4) due to iodinated inhibitors of T4 monodeiodination indicative of hyperthyroidism? J Clin Endocrinol Metab 1982; 55: 1058–1065.
9.
Nademanee K, Singh BN, Callahan B, Hendrickson JA, Hershman JM: Amiodarone, thyroid indexes, and altered thyroid function: long-term serial effects in patients with cardiac arrhythmias. Am J Cardiol1986; 58: 981–986.
10.
Franklyn JA, Davis JR, Gammage MD, Littler WA, Ramsden DB, Sheppard MC: Amiodarone and thyroid hormone action. Clin Endocrinol (Oxf)1985; 22: 257–264.
11.
Yamazaki K, Mitsuhashi T, Yamada E, Yamada T, Kosaka S, Takano K, Obara T, Sato: Amiodarone reversibly decreases sodium-iodide symporter mRNA expression at therapeutic concentrations and induces antioxidant responses at supraphysiological concentrations in cultured human thyroid follicles. Thyroid 2007; 17: 1189–1200.
12.
Melmed S, Nademanee K, Reed AW, Hendrickson JA, Singh BN, Hershman JM: Hyperthyroxinemia with bradycardia and normal thyrotropin secretion after chronic amiodarone administration. J Clin Endocrinol Metab 1981; 53: 997–1001.
13.
Hershman JM, Nademanee K, Sugawara M, Pekary AE, Ross R, Singh BN, DiStefano JJ 3rd: Thyroxine and triiodothyronine kinetics in cardiac patients taking amiodarone. Acta Endocrinol (Copenh) 1986; 111: 193–199.
14.
Amico JA, Richardson V, Alpert B, Klein I: Clinical and chemical assessment of thyroid function during therapy with amiodarone. Arch Intern Med 1984; 144: 487–490.
15.
Unger J, Lambert M, Jonckheer MH, Denayer P: Amiodarone and the thyroid: pharmacological, toxic and therapeutic effects. J Intern Med 1993; 233: 435–443.
16.
Wiersinga WM, Trip MD: Amiodarone and thyroid hormone metabolism. Postgrad Med J 1986; 62: 909–914.
17.
Batcher EL, Tang XC, Singh BN, Singh SN, Reda DJ, Hershman JM; SAFE-T Investigators: Thyroid function abnormalities during amiodarone therapy for persistent atrial fibrillation. Am J Med 2007; 120: 880–885.
18.
Zhong B, Wang Y, Zhang G, Wang Z: Environmental iodine content, female sex and age are associated with new-onset amiodarone-induced hypothyroidism: a systematic review and meta-analysis of adverse reactions of amiodarone on the thyroid. Cardiology 2016; 134: 366–371.
19.
Bogazzi F, Tomisti L, Bartalena L, Aghini-Lombardi F, Martino E: Amiodarone and the thyroid: a 2012 update. J Endocrinol Invest 2012; 35: 340–348.
20.
Harjai K, Licata A: Effects of Amiodarone on thyroid function. Ann Intern Med 1997; 126: 63–73.
21.
Stott DJ, Rodondi N, Kearney PM, Ford I, Westendorp RGJ, Mooijaart SP, Sattar N, Aubert CE, Aujesky D, Bauer DC, Baumgartner C, Blum MR, Browne JP, Byrne S, Collet TH, Dekkers OM, denElzen WPJ, DuPuy RS, Ellis G, Feller M, Floriani C, Hendry K, Hurley C, Jukema JW, Kean S, Kelly M, Krebs D, Langhorne P, McCarthy G, McCarthy V, McConnachie A, McDade M, Messow M, O’Flynn A, O’Riordan D, Poortvliet RKE, Quinn TJ, Russell A, Sinnott C, Smit JWA, Van Dorland HA, Walsh KA, Walsh EK, Watt T, Wilson R, Gussekloo J; TRUST Study Group: Thyroid hormone therapy for older adults with subclinical hypothyroidism. N Engl J Med 2017; 376: 2534–2544.
22.
Benjamens S, Dullaart RPF,Sluiter WJ, Rienstra M, van Gelder IC, Links TP: The clinical value of regular thyroid function tests during amiodarone treatment. Eur J Endocrinol 2017; 177: 9–14.
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: 116–130.
24.
Theodoraki A, Vanderpump MPJ: Thyrotoxicosis associated with the use of amiodarone: the utility of ultrasound in patient management. Clin Endocrinol (Oxf) 2016; 84: 172–176.
25.
Bogazzi F, Bartalena L, Dell’Unto E, Tomisti L, Rossi G, Pepe P, Tanda ML, Grasso L, Macchia E, Aghini-Lombardi F, Pinchera A, Martino E: Proportion of type 1 and type 2 amiodarone-induced thyrotoxicosis has changed over a 27-year period in Italy. Clin Endocrinol (Oxf) 2007; 67: 533–537.
26.
Balzano S, Sau F, Bartalena L, Ruscazio M, Balestrieri A, Cherchi A, Martino E: Diagnosis of amiodarone-iodine-induced thyrotoxicosis (AIIT) associated with severe nonthyroidal illness. J Endocrinol Invest 1987; 10: 589–591.
27.
Tomisti L, Urbani C, Rossi G, Latrofa F, Sardella C, Manetti L, Lupi I, Marcocci C, Bartalena L, Curzio O, Martino E, Bogazzi F: The presence of anti-thyroglobulin (TgAb) and/or anti-thyroperoxidase antibodies (TPOAb) does not exclude the diagnosis of type 2 amiodarone-induced thyrotoxicosis. J Endocrinol Invest 2016; 39: 585–591.
28.
Piga M, Cocco MC, Serra A, Boi F, Loy M, Mariotti S: The usefulness of 99mTc-sestaMIBI thyroid scan in the differential diagnosis and management of amiodarone-induced thyrotoxicosis. Eur J Endocrinol 2008; 159: 423–429.
29.
Pattison DA, Westcott J, Lichtenstein M, Toh HB, Gunawardana D, Better N, Forehan S, Sivaratnam D: Quantitative assessment of thyroid-to-background ratio improves the interobserver reliability of technetium-99m sestamibi thyroid scintigraphy for investigation of amiodarone-induced thyrotoxicosis. Nucl Med Commun 2015; 36: 356–362.
30.
Loy M, Perra E, Melis A, Cianchetti ME, Piga M, Serra A, Pinna G, Mariotti S: Color-flow Doppler sonography in the differential diagnosis and management of amiodarone-induced thyrotoxicosis. Acta Radiol 2007; 48: 628–634.
31.
Yiu KH, Jim MH, Siu CW, Lee CH, Yuen M, Mok M, Shea YF, Fan K, Tse HF, Chow WH: Amiodarone-induced thyrotoxicosis is a predictor of adverse cardiovascular outcome. J Clin Endocrinol Metab 2009; 94: 109–114.
32.
O’Sullivan AJ, Lewis M, Diamond T: Amiodarone-induced thyrotoxicosis: left ventricular dysfunction is associated with increased mortality. Eur J Endocrinol 2006; 154: 533–536.
33.
Wang TJ, Evans JC, Benjamin EJ, Levy D, LeRoy EC, Vasan RS: Natural history of asymptomatic left ventricular systolic dysfunction in the community. Circulation 2003; 108: 977–982.
34.
Tomisti L, Del Re M, Bartalena L, Tanda ML, Pucci A, Pambianco M, Danesi R, Braverman LE, Martino E, Bogazzi F: Effects of amiodarone, thyroid hormones and CYP2C9 and VKORC1 polymorphisms on warfarin metabolism: a review of the literature. Endocr Pract 2013; 19: 1043–1049.
35.
Tomisti L, Materazzi G, Bartalena L, Rossi G, Marchello A, Moretti M, De Napoli L, Mariotti R, Miccoli P, Martino E, Bogazzi F: Total thyroidectomy in patients with amiodarone-induced thyrotoxicosis and severe left ventricular systolic dysfunction. J Clin Endocrinol Metab 2012; 97: 3515–3521.
36.
Pierret C, Tourtier JP, Pons Y, Merat S, Duverger V, Perrier E: Total thyroidectomy for amiodarone-associated thyrotoxicosis: should surgery always be delayed for pre-operative medical preparation? J Laryngol Otol 2012; 126: 701–705.
37.
Kaderli RM, Fahrner R, Christ ER, Stettler C, Fuhrer J, Martinelli M, Vogt A, Seiler CA: Total thyroidectomy for amiodarone-induced thyrotoxicosis in the hyperthyroid state. Exp Clin Endocrinol Diabetes 2016; 124: 45–48.
38.
Zhu L, Zainudin SB, Kaushik M, Khor LY, Chng CL: Plasma exchange in the treatment of thyroid storm secondary to type II amiodarone-induced thyrotoxicosis. Endocrinol Diabetes Metab Case Rep 2016; 2016: 160039.
39.
Eskes SA, Endert E, Fliers E, GerskusRB, Dullaart RP, Links TP, Wiersinga WM: Treatment of amiodarone-induced thyrotoxicosis type 2: a randomized clinical trial. J Clin Endocrinol Metab 2012; 87: 499–506.
40.
Uzan L, Guignat L, Meune C, Mouly S, Weber S, Bertagna X, Bertherat J, Thomopoulos P, Duboc D: Continuation of amiodarone therapy despite type II amiodarone-induced thyrotoxicosis. Drug Saf 2006; 29: 231–236.
41.
Sato K, Shiga T, Matsuda N, Onoda N, Takano K, Hagiara N, Kasanuki H: Mild and short recurrence of type II amiodarone-induced thyrotoxicosis in three patients receiving amiodarone continuously for more than 10 years. Endocrine J 2006; 53: 531–538.
42.
Bogazzi F, Bartalena L, Tomisti L, Rossi G, Brogioni S, Martino E: 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: 3374–3380.
43.
Eskes SA, Wiersinga WM: Amiodarone and thyroid. Best Pract Res Clin Endocrinol Metab 2009; 23: 735–751.
44.
Jabrocka-Hybel A, Bednarczuk T, Bartalena L, Pach D, Ruchała M, Kamiński G, Kostecka-Matyja M, Hubalewska-Dydejczyk A: Amiodarone and the thyroid. Endokrynol Pol 2015; 66: 176–186.
45.
Bogazzi F, Tomisti L, Rossi G, Dell’Unto E, Pepe P, Bartalena L, Martino E: 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: 3757–3762.
46.
Bogazzi F, Bartalena L, Cosci C, Brogioni S, Dell’Unto E, Grasso L, Aghini-Lombardi F, Rossi G, Pinchera A, Braverman LE, Martino E: Treatment of type II amiodarone-induced thyrotoxicosis by either iopanoic acid or glucocorticoids: a prospective, randomized study. J Clin Endocrinol Metab 2003; 88: 1999–2002.
47.
Dickstein G, Shechner C, Adawi F, Kaplan J, Baron E, Ish-Shalom S: Lithium treatment in amiodarone-induced thyrotoxicosis. Am J Med 1997; 102: 454–458.
48.
Han TS, Williams GR, Vanderpump MPJ: Benzofuran derivatives and the thyroid. Clin Endocrinol (Oxf) 2009; 70: 2–13.
49.
Bogazzi F, Bartalena L, Tomisti L, Rossi G, Tanda ML, Dell’Unto E, Aghini-Lombardi F, Martino E: 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: 556–562.
50.
Vanderpump MPJ: Use of glucocorticoids in amiodarone-induced thyrotoxicosis. Nat Rev Endocrinol 2009; 5: 650–651.
51.
Albino CC, Paz-Filho G, Graf H: Recombinant human TSH as an adjuvant to radioiodine for the treatment of type 1 amiodarone-induced thyrotoxicosis (AIT). Clin Endocrinol (Oxf) 2009; 70: 810–811.
52.
Bogazzi F, Tomisti L, Ceccarelli C, Martino E: Recombinant human TSH as an adjuvant to radioiodine for the treatment of type 1 amiodarone-induced thyrotoxicosis: a cautionary note. Clin Endocrinol (Oxf) 2010; 72: 133–134.
53.
Houghton SG, Farley DR, Brennan MD, van Heerden JA, Thompson GB, Grant CS: Surgical management of amiodarone-associated thyrotoxicosis: Mayo Clinic experience. World J Surg 2004; 28: 1083–1087.
54.
Gough J, Gough IR: Total thyroidectomy for amiodarone-associated thyrotoxicosis in patients with severe cardiac disease. World J Surg 2006; 30: 1957–1961.
55.
Maqdasy S, Batisse-Lignier M, Auclair C, Desbiez F, Citron B, Thieblot P, Roche B, Lusson JR, Tauveron I: Amiodarone-induced thyrotoxicosis recurrence after amiodarone reintroduction. Am J Cardiol 2016; 117: 1112–1116.
56.
Ryan LE, Braverman LE, Cooper DS, Ladenson PW, Kloos RT: Can amiodarone be restarted after amiodarone-induced thyrotoxicosis? Thyroid 2004; 14: 149–153.
Copyright / Drug Dosage / Disclaimer
Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.
You do not currently have access to this content.