How does amiodarone (antiarrhythmic medication) affect thyroid function tests?

From the Guidelines

Amiodarone can significantly interfere with thyroid function tests due to its high iodine content and direct effects on thyroid hormone metabolism, causing both falsely abnormal test results and actual thyroid dysfunction, as noted in studies such as 1 and 1.

Effects on Thyroid Function Tests

Amiodarone can increase T4 levels and decrease T3 levels even in euthyroid patients, making interpretation challenging. TSH may initially rise then normalize in patients without true thyroid disease.

• The drug's high iodine content is a factor in its effects on the thyroid gland, as discussed in 1.
• Amiodarone structurally resembles thyroid hormones and has a very long half-life (up to 100 days), meaning its impact on thyroid tests can persist for months after discontinuation, as mentioned in 1.

Monitoring Thyroid Function

When monitoring thyroid function in patients on amiodarone, it's essential to:

• Establish baseline thyroid tests before starting the medication, as suggested in 1.
• Monitor regularly (typically every 3-6 months) during treatment, considering the expected amiodarone effects: elevated T4, decreased T3, and potentially transient TSH abnormalities.
• Evaluate abnormal results in clinical context, as true amiodarone-induced thyroid dysfunction occurs in about 15-20% of patients, presenting as either hypothyroidism or thyrotoxicosis, as noted in 1 and 1.

Clinical Considerations

• The effects of amiodarone on thyroid function are due to its complex pharmacokinetics and multiple electrophysiologic effects, as discussed in 1.
• Laboratory studies to assess liver and thyroid function should be performed at least every six months, as recommended in 1.
• The dosage of amiodarone should be kept at the lowest effective level to minimize potential drug toxicity and interactions, as suggested in 1.

From the FDA Drug Label

Amiodarone inhibits peripheral conversion of thyroxine (T 4) to triiodothyronine (T 3) and may cause increased thyroxine levels, decreased T 3 levels, and increased levels of inactive reverse T 3 (rT 3) in clinically euthyroid patients. Because of the slow elimination of amiodarone and its metabolites, high plasma iodide levels, altered thyroid function, and abnormal thyroid-function tests may persist for several weeks or even months following amiodarone withdrawal. Hypothyroidism has been reported in 2 to 4% of patients in most series, but in 8 to 10% in some series This condition may be identified by relevant clinical symptoms and particularly by elevated serum TSH levels. Hyperthyroidism is best identified by relevant clinical symptoms and signs, accompanied usually by abnormally elevated levels of serum T 3 RIA, and further elevations of serum T 4, and a subnormal serum TSH level (using a sufficiently sensitive TSH assay)

Amiodarone can affect thyroid testing by:

• Inhibiting peripheral conversion of T4 to T3, leading to increased T4 levels and decreased T3 levels
• Increasing levels of inactive reverse T3 (rT3)
• Causing abnormal thyroid-function tests due to high plasma iodide levels and altered thyroid function
• Persisting for several weeks or months after amiodarone withdrawal, making it essential to monitor thyroid function periodically 2 Key points to consider:
• Elevated serum TSH levels may indicate hypothyroidism
• Abnormally elevated levels of serum T3 RIA and subnormal serum TSH level may indicate hyperthyroidism

From the Research

Effects of Amiodarone on Thyroid Testing

• Amiodarone can cause thyroid dysfunction, including amiodarone-induced thyrotoxicosis (AIT) and amiodarone-induced hypothyroidism (AIH) 3, 4, 5, 6.
• The drug's high iodine content and structural similarity to thyroid hormones may contribute to its effects on the thyroid gland and thyroid hormone metabolism 3, 6.
• Patients receiving amiodarone treatment should be monitored for signs of thyroid dysfunction, with initial tests including thyroid-stimulating hormone, thyroxine, triiodothyronine, and antithyroid antibodies 3.

Types of Amiodarone-Induced Thyroid Dysfunction

• AIT can be classified into two types: type 1, which occurs in patients with known or previously undiagnosed thyroid dysfunction or goiter, and type 2, which occurs in normal thyroid glands and results in destruction of thyroid tissue caused by thyroiditis 3, 5.
• AIH is diagnosed and managed in the same way as usual cases of hypothyroidism, with treatment involving thyroid hormone replacement therapy 4, 5.

Monitoring and Diagnosis

• Regular monitoring of thyroid function tests is recommended for patients receiving amiodarone treatment, although the yield of regular testing in predicting overt thyroid dysfunction is uncertain 7.
• Subclinical thyroid dysfunction may precede overt thyroid dysfunction in some patients, but not all cases of AIT or AIH are preceded by subclinical events 7.
• Diagnosis and management of amiodarone-induced thyroid dysfunction can be challenging, particularly in cases of mixed-type AIT 3, 4, 6.