Can Amiodarone (antiarrhythmic medication) cause hypothyroidism (thyroid hypoactivity)?

Amiodarone and Thyroid Dysfunction

Yes, amiodarone commonly causes hypothyroidism, with hypothyroidism occurring two to four times more frequently than hyperthyroidism in patients taking this medication. 1

Mechanism of Amiodarone-Induced Hypothyroidism

Amiodarone affects thyroid function through several mechanisms:

• It inhibits peripheral conversion of thyroxine (T4) to triiodothyronine (T3)
• It releases large amounts of inorganic iodine (each 200 mg tablet contains 75 mg of iodine)
• It may cause direct thyroid tissue damage 2

These effects can result in:

• Increased thyroxine (T4) levels
• Decreased T3 levels
• Increased levels of inactive reverse T3 (rT3) 2

Epidemiology

• Hypothyroidism occurs in approximately 2-4% of patients in most studies, but rates of 8-10% have been reported in some series 2
• Hypothyroidism is more common than hyperthyroidism, occurring 2-4 times more frequently 1
• Risk is higher in areas with sufficient dietary iodine intake 3
• Patients with underlying thyroid abnormalities, especially Hashimoto's thyroiditis, are at increased risk 3, 4
• Presence of thyroid autoantibodies represents a significant risk factor 4

Clinical Presentation

Hypothyroidism due to amiodarone presents similarly to other forms of hypothyroidism:

• Elevated TSH levels
• Clinical symptoms of hypothyroidism (fatigue, cold intolerance, weight gain, constipation)
• In some clinically hypothyroid patients, free thyroxine index values may remain normal 2

Monitoring and Management

Monitoring

• Thyroid function should be monitored prior to starting amiodarone and periodically thereafter 2
• More vigilant monitoring is recommended for:
  • Elderly patients
  • Patients with history of thyroid nodules, goiter, or other thyroid dysfunction
  • Patients with thyroid autoantibodies 2, 4

Management

1. Hypothyroidism is best managed by:

   • Amiodarone dose reduction if possible
   • Thyroid hormone supplementation (levothyroxine) 2, 3

2. Continuation of amiodarone:

   • In hypothyroid patients with strong clinical indications for amiodarone, the drug may often be continued with appropriate thyroid hormone supplementation 1
   • Therapy must be individualized, and discontinuation of amiodarone may be necessary in some patients 2

3. Duration of hypothyroidism:

   • Patients without underlying thyroid disease often have transient hypothyroidism that resolves after amiodarone withdrawal
   • Patients with underlying thyroid abnormalities, especially those with thyroid autoantibodies, may develop persistent hypothyroidism 4

Important Considerations

• Due to amiodarone's long half-life, altered thyroid function and abnormal thyroid function tests may persist for several weeks or even months following amiodarone withdrawal 2
• Regular monitoring of thyroid function is essential throughout treatment with amiodarone
• The frequency of adverse effects relates to total amiodarone exposure (dosage and duration of treatment) 1

Comparison with Amiodarone-Induced Hyperthyroidism

While hypothyroidism is more common, hyperthyroidism (occurring in about 2% of patients) generally poses a greater hazard due to:

• Possibility of thyrotoxicosis
• Arrhythmia breakthrough or aggravation
• Potential for death associated with amiodarone-induced thyrotoxicosis 2

When thyroid dysfunction occurs, determining whether it's hypothyroidism or hyperthyroidism is crucial for appropriate management, as the treatments differ significantly.