Amiodarone and the thyroid: A 2012 update

Journal of Endocrinological Investigation

Volumn 35, Issue 3, 2012, Pages 340-348

  Bogazzi, F ^a   Tomisti, L ^a   Bartalena, L ^b   Aghini Lombardi, F ^a   Martino, E ^a  

^a UNIVERSITY OF PISA   (Italy)

^b UNIVERSITY OF INSUBRIA   (Italy)

Author keywords

Amiodarone; Amiodarone induced hypothyroidism; Amiodarone induced thyrotoxicosis; Hyperthyroidism; Iodine; Thyroid

Indexed keywords

ADENOSINE TRIPHOSPHATASE (POTASSIUM SODIUM); AMIODARONE; APOPTOSIS INDUCING FACTOR; CYTOCHROME C; DEETHYLAMIODARONE; DRONEDARONE; GLUCOCORTICOID; IODINE; PLACEBO; POTASSIUM PERCHLORATE; RADIOACTIVE IODINE; THIONAMIDE DERIVATIVE; THYROID HORMONE; THYROTROPIN; THYROXINE;

ANTIARRHYTHMIC ACTIVITY; AUTOIMMUNE THYROIDITIS; CARDIOVASCULAR RISK; CHEMICAL STRUCTURE; CLINICAL FEATURE; CYTOTOXICITY; DESTRUCTIVE THYROIDITIS; DIAGNOSTIC PROCEDURE; DRUG APPROVAL; DRUG EFFICACY; DRUG HALF LIFE; DRUG MECHANISM; DRUG SAFETY; DRUG UPTAKE; FREE THYROXINE INDEX; GRAVES DISEASE; HEART ATRIUM FIBRILLATION; HEART ATRIUM FLUTTER; HEART DISEASE; HORMONE DETERMINATION; HUMAN; HYPOTHYROIDISM; LIVER FAILURE; LUNG TOXICITY; PREVALENCE; REVIEW; RISK ASSESSMENT; THYROID DISEASE; THYROID FUNCTION TEST; THYROID HORMONE SYNTHESIS; THYROID TOXICITY; THYROIDECTOMY; THYROTOXICOSIS; TOXICITY;

AMIODARONE; ANTI-ARRHYTHMIA AGENTS; ATRIAL FIBRILLATION; HUMANS; HYPOTHYROIDISM; THYROXINE;

EID: 84862900325     PISSN: 03914097     EISSN: 17208386     Source Type: Journal    
DOI: 10.3275/8298     Document Type: Review

References (88)

1. Martino E, Bartalena L, Bogazzi F, Braverman LE. The effects of amiodarone on the thyroid. Endocr Rev 2001, 22: 240-54.
2. Bogazzi F, Bartalena L, Gasperi M, Braverman LE, Martino E. The various effects of amiodarone on thyroid function. Thyroid 2001, 11: 511-9.
3. rd, Waldo AL, Prystowsky EN, DiBianco R. A consensus report on antiarrhythmic drug use. Clin Cardiol 1994, 17: 103-16.
4. Burger A, Dinichert D, Nicod P, Jenny M, Lemarchand-Beraud T, Vallotton MB. Effect of amiodarone on serum triiodothyronine, reverse triiodothyronine, thyroxin, and thyrotropin. A drug influencing peripheral metabolism of thyroid hormones. J Clin Invest 1976, 58: 255-9.
5. 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.
6. Stoykov I, van Beeren HC, Moorman AF, Christoffels VM,Wiersinga WM, Bakker O. Effect of amiodarone and dronedarone administration in rats on thyroid hormone-dependent gene expression in different cardiac components. Eur J Endocrinol 2007, 156: 695-702.
7. Kahaly GJ, Dillmann WH. Thyroid hormone action in the heart. Endocr Rev 2005, 26: 704-28.
8. Bogazzi F, Bartalena L, Brogioni S, et al. Desethylamiodarone antagonizes the effect of thyroid hormone at the molecular level. Eur J Endocrinol 2001, 145: 59-64.
9. Hudig F, Bakker O, Wiersinga WM. Amiodarone decreases gene expression of low-density lipoprotein receptor at both the mRNA and the protein level. Metabolism 1998, 47: 1052-7.
10. Bakker O, van Beeren HC, Wiersinga WM. Desethylamiodarone is a noncompetitive inhibitor of the binding of thyroid hormone to the thyroid hormone beta 1-receptor protein. Endocrinology 1994, 134: 1665-70.
11. van Beeren HC, Bakker O, Wiersinga WM. Desethylamiodarone is a competitive inhibitor of the binding of thyroid hormone to the thyroid hormone alpha 1-receptor protein. Mol Cell Endocrinol 1995, 112: 15-9.
12. Rao RH, McCready VR, Spathis GS. Iodine kinetic studies during amiodarone treatment. J Clin Endocrinol Metab 1986, 62: 563-8.
13. Plomp TA, van Rossum JM, Robles de Medina EO, van Lier T, Maes RA. Pharmacokinetics and body distribution of amiodarone in man. Arzneimittelforschung 1984, 34: 513-20.
14. Doval HC, Nul DR, Grancelli HO, Perrone SV, Bortman GR, Curiel R. Randomised trial of low-dose amiodarone in severe congestive heart failure. Grupo de Estudio de la Sobrevida en la Insuficiencia Cardiaca en Argentina (GESICA). Lancet 1994, 344: 493-8.
15. Aanderud S, Sundsfjord J, Aarbakke J. Amiodarone inhibits the conversion of thyroxine to triiodothyronine in isolated rat hepatocytes. Endocrinology 1984, 115: 1605-8.
16. Hershman JM, Nademanee K, Sugawara M, et al. Thyroxine and triiodothyronine kinetics in cardiac patients taking amiodarone. Acta Endocrinol (Copenh) 1986, 111: 193-9.
17. Wolff J, Chaikoff IL, Goldberg RC, Meier JR. The temporary nature of the inhibitory action of excess iodine on organic iodine synthesis in the normal thyroid. Endocrinology 1949, 45: 504-13.
18. Tedelind S, Larsson F, Johanson C, et al. Amiodarone inhibits thyroidal iodide transport in vitro by a cyclic adenosine 5′-monophosphate-and iodine-independent mechanism. Endocrinology 2006, 147: 2936-43.
19. Yamazaki K, Mitsuhashi T, Yamada E, et al. 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: 1189-200.
20. 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: 227-37.
21. Bogazzi F, Bartalena L, Tomisti L, et al. Potassium perchlorate only temporarily restores euthyroidism in patients with amiodarone-induced hypothyroidism who continue amiodarone therapy. J Endocrinol Invest 2008, 31: 515-9.
22. Beddows SA, Page SR, Taylor AH, et al. Cytotoxic effects of amiodarone and desethylamiodarone on human thyrocytes. Biochem Pharmacol 1989, 38: 4397-403.
23. Vitale M, Di Matola T, D'Ascoli F, et al. Iodide excess induces apoptosis in thyroid cells through a p53-independent mechanism involving oxidative stress. Endocrinology 2000, 141: 598-605.
24. Di Matola T, D'Ascoli F, Fenzi G, et al. Amiodarone induces cytochrome c release and apoptosis through an iodine-independent mechanism. J Clin Endocrinol Metab 2000, 85: 4323-30.
25. Chiovato L,Martino E, TonaccheraM, et al. Studies on the in vitro cytotoxic effect of amiodarone. Endocrinology 1994, 134: 2277-82.
26. Pitsiavas V, Smerdely P, Li M, Boyages SC. Amiodarone induces a different pattern of ultrastructural change in the thyroid to iodine excess alone in both the BB/W rat and the Wistar rat. Eur J Endocrinol 1997, 137: 89-98.
27. 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: 177-83.
28. Trip MD, Wiersinga W, Plomp TA. Incidence, predictability, and pathogenesis of amiodarone-induced thyrotoxicosis and hypothyroidism. Am J Med 1991, 91: 507-11.
29. Martino E, Safran M, Aghini-Lombardi F, et al. Environmental iodine intake and thyroid dysfunction during chronic amiodarone therapy. Ann Intern Med 1984, 101: 28-34.
30. Martino E, Aghini-Lombardi F, Mariotti S, Bartalena L, Braverman L, Pinchera A. Amiodarone: a common source of iodine-induced thyrotoxicosis. Horm Res 1987, 26: 158-71.
31. Eskes SA, Wiersinga WM. Amiodarone and thyroid. Best Pract Res Clin Endocrinol Metab 2009, 23: 735-51.
32. Bartalena L, Wiersinga WM, Tanda ML, 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) 2004, 61: 494-502.
33. Diehl LA, Romaldini JH, Graf H, et al. Management of amiodarone-induced thyrotoxicosis in Latin America: an electronic survey. Clin Endocrinol (Oxf) 2006, 65: 433-8.
34. Tanda ML, Piantanida E, Lai A, et al. Diagnosis and management of amiodarone-induced thyrotoxicosis: similarities and differences between North American and European thyroidologists. Clin Endocrinol (Oxf) 2008, 69: 812-8.
35. 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: 533-7.
36. Newnham HH, Topliss DJ, Le Grand BA, Chosich N, Harper RW, Stockigt JR. Amiodarone-induced hyperthyroidism: assessment of the predictive value of biochemical testing and response to combined therapy using propylthiouracil and potassium perchlorate. Aust N Z J Med 1988, 18: 37-44.
37. Nademanee K, Singh BN, Callahan B, Hendrickson JA, Hershman JM. Amiodarone, thyroid hormone indexes, and altered thyroid function: long-term serial effects in patients with cardiac arrhythmias. Am J Cardiol 1986, 58: 981-6.
38. Mariotti S, Loviselli A, Murenu S, et al. High prevalence of thyroid dysfunction in adult patients with beta-thalassemia major submitted to amiodarone treatment. J Endocrinol Invest 1999, 22: 55-63.
39. Stelfox HT, Ahmed SB, Fiskio J, Bates DW. Monitoring amiodarone's toxicities: recommendations, evidence, and clinical practice. Clin Pharmacol Ther 2004, 75: 110-22.
40. Burgess C, Blaikie A, Ingham T, Robinson G, Narasimhan S. Monitoring the use of amiodarone: compliance with guidelines. Intern Med J 2006, 36: 289-93.
41. Bickford CL, Spencer AP. Adherence to the NASPE guideline for amiodarone monitoring at a medical university. J Manag Care Pharm 2006, 12: 254-9.
42. Raebel MA, Carroll NM, Simon SR, et al. Liver and thyroid monitoring in ambulatory patients prescribed amiodarone in 10 HMOs. J Manag Care Pharm 2006, 12: 656-64.
43. Safran M, Martino E, Aghini-Lombardi F, et al. Effect of amiodarone on circulating antithyroid antibodies. BMJ 1988, 297: 456-7.
44. Foresti V, Pepe R, Parisio E, Scolari N, Zubani R, Bianco M. Anti-thyroid antibodies during amiodarone treatment. Acta Endocrinol (Copenh) 1989, 121: 203-6.
45. Basaria S, Cooper DS. Amiodarone and the thyroid. Am J Med 2005, 118: 706-14.
46. Hawthorne GC, Campbell NP, Geddes JS, et al. Amiodarone-induced hypothyroidism. A common complication of prolonged therapy: a report of eight cases. Arch Intern Med 1985, 145: 1016-9.
47. Wiersinga WM, Touber JL, Trip MD, van Royen EA. Uninhibited thyroidal uptake of radioiodine despite iodine excess in amiodarone- induced hypothyroidism. J Clin Endocrinol Metab 1986, 63: 485-91.
48. Eaton SE, Euinton HA, Newman CM, Weetman AP, Bennet WM. Clinical experience of amiodarone-induced thyrotoxicosis over a 3-year period: role of colour-flow Doppler sonography. Clin Endocrinol (Oxf) 2002, 56: 33-8.
49. Franklyn JA, Gammage MD. Treatment of amiodarone-associated thyrotoxicosis. Nat Clin Pract Endocrinol Metab 2007, 3: 662-6.
50. Daniels GH. Amiodarone-induced thyrotoxicosis. J Clin Endocrinol Metab 2001, 86: 3-8.
51. Erdogan MF, Güleç S, Tutar E, Baskal N, Erdogan G. A stepwise approach to the treatment of amiodarone-induced thyrotoxicosis. Thyroid 2003, 13: 205-9.
52. 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: 167-73.
53. Martino E, Aghini-Lombardi F, Lippi F, et al. Twenty-four hour radioactive iodine uptake in 35 patients with amiodarone associated thyrotoxicosis. J Nucl Med 1985, 26: 1402-7.
54. Bogazzi F, Bartalena L, Brogioni S, et al. Color flow Doppler sonography rapidly differentiates type I and type II amiodarone-induced thyrotoxicosis. Thyroid 1997, 7: 541-5.
55. Loy M, Perra E, Melis A, et al. Color-flow Doppler sonography in the differential diagnosis and management of amiodarone-induced thyrotoxicosis. Acta Radiol 2007, 48: 628-34.
56. Macedo TA, Chammas MC, Jorge PT, et al. Differentiation between the two types of amiodarone-associated thyrotoxicosis using duplex and amplitude Doppler sonography. Acta Radiol 2007, 48: 412-21.
57. 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: 423-9.
58. Tanda ML, Bogazzi F, Martino E, Bartalena L. Amiodarone-induced thyrotoxicosis: something new to refine the initial diagnosis? Eur J Endocrinol 2008, 159: 359-61.
59. Conen D, Melly L, Kaufmann C, et al. Amiodarone-induced thyrotoxicosis: clinical course and predictors of outcome. J Am Coll Cardiol 2007, 49: 2350-5.
60. Keidar S, Grenadier E, Palant A. Amiodarone-induced thyrotoxicosis: four cases and a review of the literature. Postgrad Med J 1980, 56: 356-8.
61. Lu Y,Won KA, Nelson BJ, Qi D, Rausch DJ, Asinger RW. Characteristics of the amiodarone-warfarin interaction during long-term follow- up. Am J Health Syst Pharm 2008, 65: 947-52.
62. Kurnik D, Loebstein R, Farfel Z, Ezra D, Halkin H, Olchovsky D. Complex drug-drug-disease interactions between amiodarone, warfarin, and the thyroid gland. Medicine (Baltimore) 2004, 83: 107-13.
63. 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: 3757-62.
64. 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: 556-62.
65. Lorberboym M, Schachter P. Drug-induced thyrotoxicosis: the surgical option. Isr Med Assoc J 2007, 9: 79-82.
66. Hamoir E, Meurisse M, Defechereux T, Joris J, Vivario J, Hennen G. Surgical management of amiodarone-associated thyrotoxicosis: too risky or too effective? World J Surg 1998, 22: 537-42.
67. Franzese CB, Fan CY, Stack BC Jr. Surgical management of amiodarone-induced thyrotoxicosis. Otolaryngol Head Neck Surg 2003, 129: 565-70.
68. Gough J, Gough IR. Total thyroidectomy for amiodarone-associated thyrotoxicosis in patients with severe cardiac disease. World J Surg 2006, 30: 1957-61.
69. Wiersinga W. Amiodarone and the thyroid. In: Grossman A. Pharmacotherapeutics of the thyroid gland. Berlin: Springer. 1997, 129-35.
70. 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: 3374-80.
71. 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: 1999-2002.
72. Bogazzi F, Dell'Unto E, Tanda ML, et al. Long-term outcome of thyroid function after amiodarone-induced thyrotoxicosis, as compared to subacute thyroiditis. J Endocrinol Invest 2006, 29: 694-9.
73. 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: 201-7.
74. Gursoy A, Tutuncu NB, Gencoglu A, Anil C, Demirer AN, Demirag NG. Radioactive iodine in the treatment of type-2 amiodarone-induced thyrotoxicosis. J Natl Med Assoc 2008, 100: 716-9.
75. Osman F, Franklyn JA, Sheppard MC, Gammage MD. Successful treatment of amiodarone-induced thyrotoxicosis. Circulation 2002, 105: 1275-7.
76. 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: 499-506.
77. Albino CC, Paz-Filho G, Graf H. Recombinant human TSH as an adjuvant to radioiodine for the treatment of type 1 amiodaroneinduced thyrotoxicosis (AIT). Clin Endocrinol (Oxf) 2009, 70: 810-1.
78. 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: 133-4.
79. Yiu KH, Jim MH, Siu CW, et al. Amiodarone-induced thyrotoxicosis is a predictor of adverse cardiovascular outcome. J Clin Endocrinol Metab 2009, 94: 109-14.
80. O'Sullivan AJ, Lewis M, Diamond T. Amiodarone-induced thyrotoxicosis: left ventricular dysfunction is associated with increased mortality. Eur J Endocrinol 2006, 154: 533-6.
81. 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: 1114-8.
82. Bogazzi F, Aghini-Lombardi F, Cosci C, et al. Iopanoic acid rapidly controls type I amiodarone-induced thyrotoxicosis prior to thyroidectomy. J Endocrinol Invest 2002, 25: 176-80.
83. Berti P, Materazzi G, Bogazzi F, Ambrosini CE, Martino E, Miccoli P. Combination of minimally invasive thyroid surgery and local anesthesia associated to iopanoic acid for patients with amiodarone-induced thyrotoxicosis and severe cardiac disorders: a pilot study. Langenbecks Arch Surg 2007, 392: 709-13.
84. Langley RW, Burch HB. Perioperative management of the thyrotoxic patient. Endocrinol Metab Clin North Am 2003, 32: 519-34.
85. Zimetbaum PJ. Dronedarone for atrial fibrillation - an odyssey. N Engl J Med 2009, 360: 1811-3.
86. Le Heuzey JY, De Ferrari GM, Radzik D, Santini M, Zhu J, Davy JM. A short-term, randomized, double-blind, parallel-group study to evaluate the efficacy and safety of dronedarone versus amiodarone in patients with persistent atrial fibrillation: the DIONYSOS study. J Cardiovasc Electrophysiol 2010, 21: 597-605.
87. Van Beeren HC, Jong WM, Kaptein E, Visser TJ, Bakker O, Wiersinga WM. Dronerarone acts as a selective inhibitor of 3,5,3′- triiodothyronine binding to thyroid hormone receptor-alpha1: in vitro and in vivo evidence. Endocrinology 2003, 144: 552-8.
88. Singh BN, Connolly SJ, Crijns HJ, et al; EURIDIS and ADONIS Investigators. Dronedarone for maintenance of sinus rhythm in atrial fibrillation or flutter. N Engl J Med 2007, 357: 987-99.