How are amiodarone-induced thyrotoxicosis (AIT) and amiodarone-induced hypothyroidism (AIH) treated?

Updated: Aug 28, 2020
  • Author: Mini Gopalan, MD; Chief Editor: Romesh Khardori, MD, PhD, FACP  more...
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Answer

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. [6, 13]

    • 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. [6]

    • 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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