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Thyroid Dysfunction Induced by Amiodarone Therapy Treatment & Management

  • Author: Mini Gopalan, MD; Chief Editor: Romesh Khardori, MD, PhD, FACP  more...
 
Updated: Jul 12, 2016
 

Medical Care

AIT presents a therapeutic challenge because data on optimal treatment are limited because of the lack of randomized, controlled trials.

  • Differentiation of the 2 types of thyrotoxicosis is essential for determining the best management of the disease. However, one study in the United Kingdom found that the distinction between the 2 subtypes of AIT was not essential for treatment and found no difference in overall outcome between the 2 groups treated with thionamides alone. These results conflict with those of an Italian study, which found that type 2 AIT responds to steroids. This difference in results was attributed to the disparate levels of dietary iodine intake endemic to the 2 regions. The heterogeneity of patients with AIT (especially regarding iodine intake), the small number of patients studied in these trials, and the incomplete knowledge of the complex pathogenesis of the disease probably account for the contradictory results.
  • The initial management of AIT involves deciding whether to discontinue amiodarone therapy. This depends on the patient's cardiac condition, the availability of alternate therapies, and the type of AIT present in the patient. Continuation of amiodarone treatment does not alter the basic approach to the medical management of thyrotoxicosis, but it reduces the chances of a successful outcome. In type 1 thyrotoxicosis, the persistently raised levels of intrathyroidal and circulating iodide reduce the effectiveness of treatment with antithyroid drugs.
  • Mild AIT subsides spontaneously in up to 20% of cases upon discontinuation of amiodarone therapy. Many patients with type 2 AIT become euthyroid within 3-5 months after the discontinuation of amiodarone therapy. Occasionally, spontaneous remission occurs despite continued amiodarone use. Recurrences of type 2 AIT despite discontinuation of amiodarone have also been documented. Spontaneous remissions of type 1 AIT have not been documented.
    • Even if amiodarone therapy is stopped, thyrotoxicosis persists for up to 8 months because of the drug's long half-life. Discontinuation of the drug has no immediate benefit.
    • No randomized, controlled trials exist that determine the effect of stopping amiodarone therapy in patients with AIT. This decision is made in consultation with the cardiologist. Amiodarone therapy is usually continued unless it is ineffective in treating the arrhythmia or toxicity in other organs is evident. Moreover, stopping amiodarone therapy may exacerbate symptoms of thyrotoxicosis, as it blocks T4-to-T3 conversion and beta-adrenergic receptors. On the other hand, severe thyrotoxicosis may be incompatible with continuation of amiodarone treatment unless a thyroidectomy is performed.
  • Type 1 thyrotoxicosis
    • Type 1 thyrotoxicosis is treated with high doses of thionamides (eg, methimazole [40-60 mg/d] or propylthiouracil [600-800 mg/d]) to block thyroid hormone synthesis. Thionamides block hormone synthesis by blocking iodine organification and the coupling of iodotyrosines. Because of the large number of preformed thyroid hormones, the blocking effect is delayed and may take as long as 2-4 months.
    • Adding potassium perchlorate may block iodide uptake by the thyroid and deplete intrathyroidal iodine stores. Thus, perchlorate prevents further synthesis of thyroid hormones and improves the therapeutic efficacy of thionamides. Some studies have found good results with adding potassium perchlorate, and some have not. Potassium perchlorate has not been approved by the US Food and Drug Administration (FDA) for the treatment of thyrotoxicosis.
    • Because potassium perchlorate is a drug that potentially causes aplastic anemia, limit it to patients whose condition cannot be controlled by methimazole alone. The dose of perchlorate is 600-1000 mg/d. Do not administer potassium perchlorate for longer than 30 days because of serious adverse effects such as aplastic anemia, nephrotic syndrome, and agranulocytosis. Perform careful hematological examinations regularly during administration of potassium perchlorate.[7, 9]
    • Because all antithyroid drugs can cause bone marrow suppression, instruct patients to watch for signs such as fever, sore throat, or oral ulcers. The administration of thionamides is usually tapered to a low maintenance dose and is continued until amiodarone therapy is started. If amiodarone therapy is subsequently discontinued, the thionamides are continued until urine iodine levels return to normal (usually in 6-18 mo).
  • Type 2 thyrotoxicosis
    • Type 2 thyrotoxicosis is treated with a relatively long course of glucocorticoids. In addition to their membrane-stabilizing and anti-inflammatory effects, glucocorticoids reduce conversion of T4 to T3 by inhibiting type 1 5'-deiodinase activity. If the patient does not have any symptoms of thyrotoxicosis or a life-threatening arrhythmia that requires amiodarone therapy, the initial treatment would be discontinuation of amiodarone and continued monitoring of thyroid function.[7]
    • Administer prednisone at 30-40 mg/d and taper over a couple of months until free T4 levels are within the reference range. The symptoms may biochemically and clinically improve within 1 week following the start of therapy. Consider osteoporosis prophylaxis in patients at high risk for osteoporosis or in whom steroids are continued for more than 3 months.
  • When the mechanism of hyperthyroidism is uncertain, a combination of glucocorticoids and thionamides is used as initial therapy. A rapid response suggests type 2 AIT; thionamides can be tapered. A poor initial response suggests type 1 AIT; the steroids can be tapered and the patient can be treated for type 1 AIT.
  • Regardless of the chosen medical regimen, the toxic state invariably takes several weeks to control because of the large stores of preformed intrathyroidal hormones.
  • If thyrotoxicosis is exacerbated after initial control, it is usually treated with steroids. In type 1 AIT, this exacerbation may be due to mixed forms, which respond to the addition of steroids. In type 2 AIT, relapse can occur after discontinuation of corticosteroid treatment, and steroid treatment may need to be restarted.
  • If amiodarone therapy is discontinued, beta-blockers and iopanoic acid may be added to ameliorate hyperthyroid symptoms exacerbated by amiodarone withdrawal.
  • Radioactive iodine can be used in the rare patients with high radioactive iodine uptake; otherwise, the iodine of amiodarone inhibits uptake by the gland. Moreover, radioactive iodine often initially exacerbates the hyperthyroid state by releasing preformed hormone that is stored in the thyroid.
  • Plasmapheresis is an expensive treatment that has transient benefits and is usually followed by an exacerbation of AIT. The efficacy of lithium and iopanoic acid for the management of AIT has not been confirmed in large, randomized, controlled trials.
  • Thyroid ablation is a valid management option for type 1 AIT once euthyroidism has been restored, especially if amiodarone therapy must be restarted. Type 2 AIT requires strict follow-up because of possible progression to hypothyroidism, either spontaneously or after iodine re-exposure.
  • Hypothyroidism in patients with no preexisting thyroid disease often resolves after discontinuation of amiodarone therapy. However, hypothyroidism may persist after discontinuation of treatment in patients with underlying chronic autoimmune thyroiditis and high titers of anti-TPO antibodies. In this case, the patient may require permanent T4 replacement therapy. Amiodarone therapy is usually continued while T4 is used to normalize the TSH level. In view of the often-severe underlying cardiac disease, consider maintaining the serum TSH concentration in the upper half of the reference range. Levothyroxine is the drug of choice because it is not associated with the spikes in serum thyroid hormone concentrations observed in patients given L-T3, which also requires multiple daily doses. However, if amiodarone therapy is continued, larger doses of T4 are required to offset the inhibitory effects of amiodarone on the conversion of T4 to T3.
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Surgical Care

Total or near-total thyroidectomy is performed in cases of AIT that fail to respond to combination therapy with thionamides, perchlorate, and corticosteroids. Thyroidectomy is also performed in patients who need amiodarone therapy but whose resulting hyperthyroidism does not respond to medical treatment and for immediate control of a thyrotoxic state (eg, during thyroid storm) or in those with intractable arrhythmias. Treat the resulting hypothyroidism with thyroid hormone replacement. Despite the minimally elevated risk due to underlying heart disease, surgery is reasonably safe in these patients and can even be performed with local anesthesia.

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Consultations

Consultation with an endocrinologist is recommended. Consult with a cardiologist to decide whether or not to continue amiodarone therapy.

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Diet

No dietary restrictions apply, but excess amounts of iodide found in some expectorants, contrast dyes, seaweed tablets, and health food supplements should be avoided.

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Activity

Restriction of activity is prudent in elderly persons or in patients with severe thyrotoxicosis with cardiovascular symptoms. Otherwise, no activity restrictions are necessary.

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Complications

Complications include the following:

  • Hyperthyroidism, thyroid storm
  • Hypothyroidism, myxedema coma
  • Aplastic anemia secondary to perchlorate use
  • Agranulocytosis or hepatitis secondary to thionamides
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Prevention

Test baseline thyroid function in all patients starting amiodarone therapy to exclude underlying gland dysfunction that may predispose them to thyroid abnormalities after therapy begins. The serum levels of TSH, free T4, and free T3 may be reassessed after 3 months of amiodarone therapy. In patients with euthyroidism, thyroid function results may be used as reference for future comparisons. Periodically monitor serum TSH levels and other thyroid indices if TSH levels are abnormal or clinical suspicion of thyroid dysfunction exists. The threshold for performing thyroid function tests should be low in patients who are taking amiodarone or who have in the past, as type 2 AIT has an abrupt onset. Continue to measure thyroid function for at least a year after amiodarone therapy is discontinued.

Research indicates that another benzofuran-derived drug, dronedarone (Multaq), may be a useful alternative treatment for arrhythmia. Although apparently not as effective an antiarrhythmic as amiodarone, dronedarone seems to be less toxic to the thyroid.[10]  Dronedarone was approved by the FDA on July 2, 2009.

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Long-Term Monitoring

Prolonged monitoring of thyroid function tests is necessary in patients with AIT, even if they become euthyroid, as they may become hypothyroid. Recurrences are common in type 2 AIT.

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Contributor Information and Disclosures
Author

Mini Gopalan, MD Clinical Assistant Professor, Department of Medicine, Texas Tech University; Consulting Physician, Department of Internal Medicine, Midland Community Healthcare Services

Mini Gopalan, MD is a member of the following medical societies: American College of Physicians, American Medical Association, Endocrine Society, Texas Medical Association

Disclosure: Nothing to disclose.

Coauthor(s)

James Burks, MD, FACP, FACE Professor of Medicine, Program Director, Department of Medicine, Texas Tech University Health Sciences Center

James Burks, MD, FACP, FACE is a member of the following medical societies: American Association of Clinical Endocrinologists, American Diabetes Association, Endocrine Society

Disclosure: Nothing to disclose.

Specialty Editor Board

Francisco Talavera, PharmD, PhD Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Received salary from Medscape for employment. for: Medscape.

Arthur B Chausmer, MD, PhD, FACP, FACE, FACN, CNS Professor of Medicine (Endocrinology, Adj), Johns Hopkins School of Medicine; Affiliate Research Professor, Bioinformatics and Computational Biology Program, School of Computational Sciences, George Mason University; Principal, C/A Informatics, LLC

Arthur B Chausmer, MD, PhD, FACP, FACE, FACN, CNS is a member of the following medical societies: American Association of Clinical Endocrinologists, American College of Nutrition, American Society for Bone and Mineral Research, International Society for Clinical Densitometry, American College of Endocrinology, American College of Physicians, American College of Physicians-American Society of Internal Medicine, American Medical Informatics Association, Endocrine Society

Disclosure: Nothing to disclose.

Chief Editor

Romesh Khardori, MD, PhD, FACP Professor of Endocrinology, Director of Training Program, Division of Endocrinology, Diabetes and Metabolism, Strelitz Diabetes and Endocrine Disorders Institute, Department of Internal Medicine, Eastern Virginia Medical School

Romesh Khardori, MD, PhD, FACP is a member of the following medical societies: American Association of Clinical Endocrinologists, American College of Physicians, American Diabetes Association, Endocrine Society

Disclosure: Nothing to disclose.

Acknowledgements

Robert A Gabbay, MD, PhD Associate Professor of Medicine, Division of Endocrinology, Diabetes and Metabolism, Laurence M Demers Career Development Professor, Penn State College of Medicine; Director, Diabetes Program, Penn State Milton S Hershey Medical Center; Executive Director, Penn State Institute for Diabetes and Obesity

Robert A Gabbay, MD, PhD is a member of the following medical societies: American Association of Clinical Endocrinologists, American Diabetes Association, and Endocrine Society

Disclosure: Novo Nordisk Honoraria Speaking and teaching; Merck Honoraria Speaking and teaching

References
  1. Tsadok MA, Jackevicius CA, Rahme E, Essebag V, Eisenberg MJ, Humphries KH, et al. Amiodarone-induced thyroid dysfunction: brand-name versus generic formulations. CMAJ. 2011 Sep 6. 183(12):E817-23. [Medline]. [Full Text].

  2. Ahmed S, Van Gelder IC, Wiesfeld AC, Van Veldhuisen DJ, Links TP. Determinants and outcome of amiodarone-associated thyroid dysfunction. Clin Endocrinol (Oxf). 2011 Sep. 75(3):388-94. [Medline].

  3. Mosher MC. Amiodarone-induced hypothyroidism and other adverse effects. Dimens Crit Care Nurs. 2011 Mar-Apr. 30(2):87-93. [Medline].

  4. Hofmann A, Nawara C, Ofluoglu S, et al. Incidence and predictability of amiodarone-induced thyrotoxicosis and hypothyroidism. Wien Klin Wochenschr. 2008. 120(15-16):493-8. [Medline].

  5. Diederichsen SZ, Darkner S, Chen X, et al. Short-term amiodarone treatment for atrial fibrillation after catheter ablation induces a transient thyroid dysfunction: results from the placebo-controlled, randomized AMIO-CAT trial. Eur J Intern Med. 2016 Apr 26. [Medline].

  6. 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(3):366-71. [Medline].

  7. Piga M, Serra A, Boi F, et al. Amiodarone-induced thyrotoxicosis. A review. Minerva Endocrinol. 2008 Sep. 33(3):213-28. [Medline].

  8. 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 Oct. 159(4):423-9. [Medline].

  9. 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 Jun. 31(6):515-9. [Medline].

  10. Han TS, Williams GR, Vanderpump MP. Benzofuran derivatives and the thyroid. Clin Endocrinol (Oxf). 2009 Jan. 70(1):2-13. [Medline].

  11. 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 Jan. 56(1):33-8. [Medline].

  12. Hermida JS, Jarry G, Tcheng E, Moullart V, Arlot S, Rey JL. 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 Mar 1. 116(5):345-8. [Medline].

  13. Jabrocka-Hybel A, Bednarczuk T, Bartalena L, Pach D, Ruchała M, et al. Amiodarone and the thyroid. Endokrynol Pol. 2015. 66 (2):176-86. [Medline].

  14. Costache L, Mogos V, Preda C, Vulpoi C, Ungureanu MC. Therapeutic particularities in amiodarone induced thyroid disorder in patients with underlying cardiac condition. Rev Med Chir Soc Med Nat Iasi. 2014 Oct-Dec. 118 (4):959-64. [Medline].

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