Best Practice & Research Clinical Endocrinology & Metabolism
Volume 23, Issue 6 , Pages 735-751 , December 2009

Amiodarone and thyroid

  • Silvia A. Eskes, MD (Staff Physician)
    • ,
  • Wilmar M. Wiersinga, MD, PhD, FRCP (London) (Professor of Endocrinology)

      Affiliations

    • Corresponding Author InformationCorresponding author. Tel.: +31 20 5666071; Fax: +31 20 6917682.

References 

  1. Singh BN. Amiodarone as paradigm for developing new drugs for atrial fibrillation. Journal of Cardiovascular Pharmacology. 2008;52:300–305
  2. Wiersinga WM. Amiodarone and the thyroid. In:  Weetman AP,  Grossman A editor. Pharmacotherapeutics of the thyroid gland. Berlin: Springer; 1997;p. 225–287
  3. Martino E, Bartalena L, Bogazzi F, et al. The effects of amiodarone on the thyroid. Endocrine Reviews. 2001;22:240–254
  4. Rabkin SW. Effect of amiodarone on phospholipid content and composition in heart, lung, kidney and skeletal muscle: relationship to alteration in thyroid function. Pharmacology. 2006;76:129–135
  5. Yamazaki K, Mitsubashi 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;17:1189–1200
  6. Wiersinga WM. Pharmacological effects of amiodarone and dronedarone on cardiac thyroid hormone receptors. In:  Iervasi G,  Pingitore A editor. Thyroid and heart failure. Italia: Springer-Verlag; 2009;p. 89–95
  7. Bakker O, van Beeren HC, Wiersinga WM. Desethylamiodarone is a noncompetitive inhibitor of the binding of thyroid hormone to the thyroid hormone β1-receptor protein. Endocrinology. 1994;134:1665–1670
  8. Van Beeren HC, Bakker O, Wiersinga WM. Desethylamiodarone is a competitive inhibitor of thyroid hormone binding to the thyroid hormone α1-receptor. Molecular and Cellular Endocrinology. 1995;112:15–19
  9. Van Beeren HC, Bakker O, Wiersinga WM. Desethylamiodarone interferes with the binding of co-activitor GRIP to the β1-thyroid hormone receptor. FEBS Letters. 1999;450:35–38
  10. Bogazzi F, Bartalena L, Brogioni S, et al. Desethylamiodarone antagonizes the effect of thyroid hormone at the molecular level. European Journal of Endocrinology. 2001;145:59–64
  11. Pantos C, Mourouzis I, Xinaris C, et al. Thyroid hormone and “cardiac metamorphosis”: potential therapeutic implications. Pharmacology & Therapeutics. 2008;118:277–294
  12. Wiersinga WM, Trip MD, van Beeren HC, et al. An increase in plasma cholesterol independent of thyroid function during long-term amiodarone therapy. A dose-dependent relationship. Annales of Internal Medicine. 1991;114:128–132
  13. 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;47:1052–1057
  14. Van Beeren HC, Jong WM, Kaptein E, et al. Dronedarone acts as a selective inhibitor of 3,5,31-triiodothyronine binding to thyroid hormone receptor α: in vitro and in vivo evidence. Endocrinology. 2003;144:552–558
  15. Rao RH, McReady VR, Spathis GS. Iodine kinetic studies during amiodarone treatment. The Journal of Clinical Endocrinology and Metabolism. 1986;62:563–567
  16. Melmed S, Nademanee K, Reed AW, et al. Hyperthyroxinemia with bradycardia and normal thyrotropin secretion after chronic amiodarone administration. The Journal of Clinical Endocrinology and Metabolism. 1981;53:997–1001
  17. Newman CM, Price A, Davies DW, et al. Amiodarone and the thyroid: a practical guide to the management of thyroid dysfunction induced by amiodarone therapy. Heart. 1998;79:121–127
  18. Basaria S, Cooper DS. Amiodarone and the thyroid. The American Journal of Medicine. 2005;118:706–714
  19. Tanda ML, Piantanida E, Lai A, et al. Diagnosis and management of amiodarone-induced thyrotoxicosis: similarities and differences between North American and European thyroidologists. Clinical Endocrinology. 2008;69:612–618
  20. Diehl LA, Romaldini JH, Graf H, et al. Management of amiodarone-induced thyrotoxicosis in Latin America: an electronic survey. Clinical Endocrinology. 2006;65:433–438
  21. Bongard V, Delay M, Vigreux P, et al. Incidence rate of adverse drug reactions during long-term follow-up of patients newly treated with amiodarone. American Journal of Therapeutics. 2006;13:315–319
  22. Batcher EL, Tang C, Singh BN, et al. Thyroid function abnormalities during amiodarone therapy for persistent atrial fibrillation. The American Journal of Medicine. 2007;120:880–885
  23. Hofmann A, Nawara C, Ofluoglu S, et al. Incidence and predictability of amiodarone-induced thyrotoxicosis and hypothyroidism. Wiener Klinische Wochenschrift. 2008;120:493–498
  24. Goldschlager N, Epstein AE, Narcarelli G, et al. Practical guidelines for clinicians who treat patients with amiodarone. Archives of Internal Medicine. 2000;160:1741–1748
  25. Stelfox HT, Ahmed SB, Fiskio J, et al. Monitoring amiodarone's toxicities: recommendations, evidence, and clinical practice. Clinical Pharmacology & Therapeutics. 2004;75:110–122
  26. Trip MD, Wiersinga WM, Plomp TA. Incidence, predictability, and pathogenesis of amiodarone-induced thyrotoxicosis and hypothyroidism. The American Journal of Medicine. 1991;91:507–511
  27. Burgess C, Blaikic A, Ingham T, et al. Monitoring the use of amiodarone: compliance with guidelines. Internal Medicine Journal. 2006;36:289–293
  28. Bickford CL, Spencer AP. Adherence to the NASPE guideline for amiodarone monitoring at a medical university. Journal of Managed Care Pharmacy. 2006;12:254–259
  29. Raebel NA, Carroll NM, Simon SR, et al. Liver and thyroid monitoring in ambulatory patients prescribed amiodarone in 10 HMOs. Journal of Managed Care Pharmacy. 2006;12:656–664
  30. Bogazzi F, Bartalena L, Tomisti L, et al. Potassium perchlorate only temporarily restores euthyroidism in patients with amiodarone-induced hypothyroidism who continue amiodarone therapy. Journal of Endocrinological Investigation. 2008;31:515–519
  31. Wiersinga WM, Touber JL, Trip MD, et al. Uninhibited thyroidal uptake of radioiodine despite iodine excess in amiodarone-induced hypothyroidism. The Journal of Clinical Endocrinology and Metabolism. 1986;63:485–491
  32. Pitsiavas V, Smerdely P, Boyages SC. Amiodarone compared with iodine exhibits a potent and persistent inhibitory effect on TSH-stimulated cAMP production in vivo: a possible mechanism to explain amiodarone-induced hypothyroidism. European Journal of Endocrinology. 1999;140:241–249
  33. Tedelind S, Larsson F, Johanson C, et al. Amiodarone inhibits thyroidal iodide transport in vitro by a cyclic adenosine 51-monophosphate- and iodine-independent mechanism. Endocrinology. 2006;147:2936–2943
  34. Martino E, Mariotti S, Aghini-Lombardi F, et al. Short term administration of potassium perchlorate restores euthyroidism in amiodarone iodine-induced hypothyroidism. The Journal of Clinical Endocrinology and Metabolism. 1986;63:1233–1236
  35. Van Dam EWCM, Prummel MF, Wiersinga WM, et al. Treatment of amiodarone-induced hypothyroidism with potassium perchlorate. The Netherlands Journal of Medicine. 1993;42:21–24
  36. Fradkin JE, Wolff J. Iodide-induced thyrotoxicosis. Medicine. 1983;62:1–20
  37. Chiovato L, Martino E, Tonacchera M, et al. Studies on the in vitro cytotoxic effect of amiodarone. Endocrinology. 1994;134:2272–2282
  38. Pitsiavas V, Smerdely P, Li M, et al. 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. European Journal of Endocrinology. 1997;137:89–98
  39. Wiersinga WM. Towards an animal model of amiodarone-induced thyroid dysfunction. European Journal of Endocrinology. 1997;137:15–17
  40. Smyrk TC, Goellner JR, Brennan MD, et al. Pathology of the thyroid in amiodarone-associated thyrotoxicosis. The American Journal of Surgical Pathology. 1987;11:197–204
  41. Brennan MD, Erickson DL, Carney JA, et al. Nongoitrous (type II) amiodarone-associated thyrotoxicosis: evidence of follicular disruption in vitro and in vivo. Thyroid. 1995;5:177–183
  42. Bogazzi E, Dell'Unto E, Tanda ML, et al. Long-term outcome of thyroid function after amiodarone-induced thyrotoxicosis, as compared to subacute thyroiditis. Journal of Endocrinological Investigation. 2006;29:694–699
  43. 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. Clinical Endocrinology. 2007;67:533–537
  44. O'Sullivan AJ, Lewis M, Diamond T. Amiodarone-induced thyrotoxicosis: left ventricular dysfunction is associated with increased mortality. European Journal of Endocrinology. 2006;154:533–536
  45. Conen D, Melly L, Kaufmann C, et al. Amiodarone-induced thyrotoxicosis. Clinical course and predictors of outcome. Journal of the American College of Cardiology. 2007;49:2350–2355
  46. Kurt IH, Yigit T, Karademir BM. Atrial fibrillation due to late amiodarone-induced thyrotoxicosis. Clinical Drug Investigation. 2008;28:527–531
  47. Bartalena L, Grasso L, Brogioni S, et al. Serum IL-6 in amiodarone-induced thyrotoxicosis. The Journal of Clinical Endocrinology and Metabolism. 1994;78:423–427
  48. Daniels GH. Amiodarone-induced thyrotoxicosis. The Journal of Clinical Endocrinology and Metabolism. 2001;86:3–8
  49. 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. Clinical Endocrinology. 2002;56:33–38
  50. Erdogan MF, Gülec S, Tutar E. Başkal N, Erdogan G. A stepwise approach to the treatment of amiodarone-induced thyrotoxicosis. Thyroid. 2003;13:205–209
  51. Pearce EN, Bogazzi F, Martino E, et al. The prevalence of elevated serum C-reactive protein levels in inflammatory and noninflammatory thyroid disease. Thyroid. 2003;13:643–648
  52. Bogazzi F, Bartalena L, Brogioni S, et al. Color flow Doppler sonography rapidly differentiates type I and type II amiodarone-induced thyrotoxicosis. Thyroid. 1997;7:541–545
  53. Loy M, Perra E, Melis A, et al. Color-flow Doppler sonography in the differential diagnosis and management of amiodarone-induced thyrotoxicosis. Acta Radiologica. 2007;48:628–634
  54. Macedo TAA, Chammas MC, Jorge PT, et al. Differentiation between the two types of amiodarone-associated thyrotoxicosis using duplex and amplitude Doppler sonography. Acta Radiologica. 2007;48:412–421
  55. 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. European Journal of Endocrinology. 2008;159:423–429
  56. Kuzaik D, Loebstein R, Farfel Z, et al. Complex drug-drug-disease interactions between amiodarone, warfarin, and the thyroid gland. Medicine. 2004;83:107–113
  57. Trip MD, Duren DR, Wiersinga WM. Two cases of amiodarone-induced thyrotoxicosis successfully treated with a short course of antithyroid drugs while amiodarone was continued. British Heart Journal. 1994;72:266–268
  58. Dickstein G, Shechner C, Adawi F, et al. Lithium treatment in amiodarone-induced thyrotoxicosis. The American Journal of Medicine. 1997;102:454–458
  59. 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. The Journal of Clinical Endocrinology and Metabolism. 2003;88:1999–2002
  60. Houghton SG, Farley DR, Brennan MD, et al. Surgical management of amiodarone-associated thyrotoxicosis: Mayo Clinic experience. World Journal of Surgery. 2004;28:1083–1087
  61. Gough J, Gough IR. Total thyroidectomy for amiodarone-associated thyrotoxicosis in patients with severe cardiac disease. World Journal of Surgery. 2006;30:1957–1961
  62. Berti P, Materazzi G, Bogazzi F, et al. Combination of minimally invasive thyroid surgery and local anaesthesia associated to iopanoic acid for patients with amiodarone-induced thyrotoxicosis and severe cardiac disorders: a pilot study. Langenbecks Archive Surgery. 2007;392:709–713
  63. 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). Clinical Endocrinology. 2009;70:810–811
  64. Bogazzi F, Tomisti L, Ceccarelli C, et al. Recombinant human TSH as an adjuvant to radioiodine for the treatment of type 1 amiodarone-induced thyrotoxicosis: a cautionary note. Clinical Endocrinology. 2009 Mar 30;[Epub ahead of print]
  65. Gursoy A, Tutuncu NB, Gencoglu A, et al. Radioactive iodine in the treatment of type 2 amiodarone-induced thyrotoxicosis. Journal of the National Medical Association. 2008;100:706–719
  66. Osman F, Franklyn JA, Sheppard MC, et al. Successful treatment of amiodarone-induced thyrotoxicosis. Circulation. 2002;105:1275–1277
  67. Uzan L, Guignat L, Meune C, et al. Continuation of amiodarone therapy despite type II amiodarone-induced thyrotoxicosis. Drug Safety. 2006;29:231–236
  68. Franklyn JA, Gammage MD. Treatment of amiodarone-associated thyrotoxicosis. Nature Clinical Practice. Endocrinology & Metabolism. 2007;3:662–666
  69. Bogazzi F, Bartalena L, Tomisti L, et al. Glucocorticoid response in amiodarone-induced thyrotoxicosis resulting from destructive thyroditis is predicted by thyroid volume and serum free thyroid hormone concentrations. The Journal of Clinical Endocrinology and Metabolism. 2007;92:556–562
  70. Han TS, Williams GR, Vanderpump MPJ. Benzofuran derivatives and the thyroid. Clinical Endocrinology. 2009;70:2–13
  71. Ryan LE, Braverman LE, Cooper DS, et al. Can amiodarone be restarted after amiodarone-induced thyrotoxicosis?. Thyroid. 2004;14:149–153
  72. Sato K, Shiga T, Matsuda N, et al. Mild and short recurrence of type II amiodarone-induced thyrotoxicosis in three patients receiving amiodarone continuously for more than 10 years. Endocrine Journal. 2006;53:531–538
  73. Yiu K-H, Jim M-H, Siu C-W, et al. Amiodarone-induced thyrotoxicosis is a predictor of adverse cardiovascular outcome. The Journal of Clinical Endocrinology and Metabolism. 2009;94:109–114
  74. Bartalena L, Bogazzi F, Braverman LE, et al. Effects of amiodarone administration during pregnancy on neonatal thyroid function and subsequent neurodevelopment. Journal of Endocrinological Investigation. 2001;24:116–130
  75. Wegener FT, Ehrlich JR, Hohnloser SH. Dronedarone: an emerging agent with rhythm- and rate-controlling effects. Journal of Cardiovascular Electrophysiology. 2006;17(S2):17–20
  76. Pantos C, Mourouzis I, Malliopoulou V, et al. Dronedarone administration prevents body weight gain and increases tolerance of the heart to ischemic stress: a possible involvement of thyroid hormone receptor α1. Thyroid. 2005;15:16–23
  77. Singh BN, Connolly SJ, Crijns HJGM, et al. Dronedarone for maintenance of sinus rhythm in atrial fibrillation or flutter. The New England Journal of Medicine. 2007;357:987–999
  78. Hohnloser SH, Crijns HJGM, van Eickels M, et al. Effect of dronedarone on cardiovascular events in atrial fibrillation. The New England Journal of Medicine. 2009;360:668–678

PII: S1521-690X(09)00077-3

doi: 10.1016/j.beem.2009.07.001

Best Practice & Research Clinical Endocrinology & Metabolism
Volume 23, Issue 6 , Pages 735-751 , December 2009

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