Amiodarone and the Thyroid

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Amiodarone is the most effective antiarrhythmic drug that has ever been developed. Unfortunately, it is also the most toxic.

Among the many problems seen with amiodarone, thyroid disorders are some of the most common. Amiodarone-induced thyroid disease can be quite consequential, and can be difficult to recognize. Furthermore, amiodarone-induced thyroid disorders are often more difficult to treat than other kinds of thyroid disease.

How Does Amiodarone Cause Thyroid Toxicity?

Amiodarone causes thyroid problems in two main ways. First, amiodarone has a very high iodine content, and when certain people ingest large amounts of iodine they can develop thyroid disease. Second, amiodarone can have a direct toxic effect on the thyroid gland itself (producing a kind of thyroiditis), and the drug can also diminish the function of the thyroid hormones (specifically, it can reduce the conversion of T4 to T3, and can reduce the binding - and therefore the effectiveness - of T3). 

What Thyroid Problems Can Amiodarone Produce?

Amiodarone can produce either hypothyroidism (under-active thyroid) or hyperthyroidism (over-active thyroid). Various studies have given different estimates of the frequency of thyroid problems with amiodarone, but it appears that up to 30% of patients treated with amiodarone can develop hypothyroidism, and up to 10% can develop hyperthyroidism.

Because amiodarone remains in the body for many months (or even years) after the drug is stopped, thyroid problems can develop even after amiodarone is discontinued - and doctors need to remain vigilant regarding this possibility.

Amiodarone Hypothyroidism

The symptoms of hypothyroidism caused by amiodarone are very similar to those seen with other kinds of hypothyroidism, and commonly include fatigue, weight gain, foggy thinking, swelling, constipation, and depression.

Diagnosing hypothyroidism in patients taking amiodarone can be tricky. Amiodarone causes an elevation in TSH levels in almost everyone for up to 6 months, so experts recommend not making a diagnosis of amiodarone-induced hypothyroidism until it is shown that elevated TSH levels persist, or that T4 levels are low. However, if hypothyroidism is present (even if it’s subclinical hypothyroidism), it is important to make the diagnosis - especially in people with underlying heart disease.

Treating amiodarone-induced hypothyroidism is fundamentally the same as treating any other kind of hypothyroidism (that is, with oral thyroid hormone replacement), but, again, it can be relatively tricky because amiodarone can change the effectiveness of the thyroid hormones. In many cases, higher-than-usual doses of thyroid replacement medication are required to treat hypothyroid patients taking amiodarone. For this reason, many of these patients will be well-served to see an experienced endocrinologist to help manage their treatment.

Amiodarone Hyperthyroidism

There are two different mechanisms by which amiodarone causes hyperthyroidism. In some patients (those with underlying goiters, or with latent Graves’ disease), any increase in iodine ingestion can cause the thyroid to begin producing excessive amounts of thyroid hormone. And taking amiodarone presents the thyroid with a truly massive iodine load.

Second, in some individuals amiodarone can be toxic to the thyroid tissue itself, producing a destructive thyroiditis. In this condition, the destruction of thyroid tissue releases large amounts of thyroid hormone into the bloodstream. This thyroiditis eventually “burns itself out” when there is no remaining thyroid tissue to be destroyed. The patient then becomes hypothyroid. But in the meantime - a meantime that can last for months or years - hyperthyroidism is the problem.

The clinical manifestations of amiodarone-induced hyperthyroidism can differ from hyperthyroidism not caused by this drug. Because amiodarone has beta-blocking effects, and because the drug can also reduce the action of thyroid hormone, many of the typical symptoms of hyperthyroidism (such as jitteriness, nervousness, anxiety, heat sensitivity, or excessive sweating), are masked. So the doctor may not think of the diagnosis right away.

Patients with amiodarone-induced hyperthyroidism are more likely to experience worsening of cardiac symptoms. (Many patients taking this drug are taking it as a result of underlying heart disease.) So they often have worsening arrhythmias (often, the arrhythmias for which amiodarone was prescribed in the first place), worsening heart failure, worsening symptoms of coronary artery disease, low-grade fever, or weight loss for no apparent reason. Doctors who are not alert may not think of thyroid problems when such symptoms develop.

The treatment of amiodarone-induced hyperthyroid disease can be quite challenging. Thionamide drugs that block the synthesis of thyroid hormone (such as propylthiouracil - PTU), are often used. Perchlorate, which reduces the uptake of iodine by the thyroid gland, may be helpful. However, the doses of these medications needed to reduce the production of thyroid hormone are often quite high in patients taking amiodarone, and it can be a challenge to use these drugs effectively. Worse, if the hyperthyroidism is caused by amiodarone-induced thyroiditis, drugs aimed at reducing the production of thyroid hormones usually do not work at all, and a thyroidectomy (surgical thyroid-removal) is the only recourse.

Thyroid ablation with radioactive iodine - a noninvasive procedure that works quite well in typical hyperthyroidism - is generally not an option in the patient taking amiodarone. This is because the thyroid gland in these patients is already so overloaded with iodine that the thyroid’s uptake of the radioactive iodine is greatly diminished.

If the hyperthyroidism is causing heart failure, ​unstable angina, or life-threatening arrhythmias, it may become an emergency to achieve effective treatment as rapidly as possible - which is made much more difficult by the greatly reduced treatment options.  In any case, treating amiodarone-induced hyperthyroidism is complicated enough that an endocrinology specialist should almost always be involved.

Bottom Line

Thyroid disorders are common in patients taking amiodarone. These disorders can be difficult to recognize, difficult to treat, and can occasionally be life-threatening. It is important to be vigilant for the possibility of thyroid problems in anyone taking amiodarone.

The potential for thyroid side effects is just one more reason why doctors should always be reluctant to prescribe amiodarone. If they find it necessary to do so, then they should feel obligated to carefully follow these patients, for years if necessary, in order to monitor for thyroid side effects, as well as all the other side effects seen with this drug.

Sources:

Basaria S, Cooper DS. Amiodarone and the thyroid. Am J Med 2005; 118:706.

Bogazzi F, Bartalena L, Martino E. Approach to the patient with amiodarone-induced thyrotoxicosis. J Clin Endocrinol Metab 2010; 95:2529.

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