Amiodarone-Induced Thyrotoxicosis

Amiodarone induced thyrotoxicosis is thyrotoxicosis caused by amiodarone and its iodine content. Type 1 is iodine induced excess hormone synthesis in an abnormal thyroid. Type 2 is destructive thyroiditis in a normal thyroid. Mixed forms occur.

It affects about 3% of treated patients in iodine sufficient regions and up to 10% in iodine deficient regions. Type 2 is more common where iodine intake is adequate.

Amiodarone is about 37% iodine by weight, and a 200 mg tablet releases roughly 6 to 7 mg of free iodine daily. Its half life is 40 to 55 days, so thyrotoxicosis can start months after starting and up to a year after stopping.

Pathophysiology.

Type 1: the iodine load drives synthesis in nodular goitre or latent Graves disease, with failure of the normal escape from iodine inhibition.

Type 2: amiodarone and its metabolite are directly toxic to follicular cells, releasing preformed hormone. Uptake is low in type 2 and low, normal or high in type 1.

• Palpitations, tremor, weight loss, sweating and heat intolerance. Features may be masked by amiodarone and beta blockers.
• Recurrent or worsening arrhythmia, new atrial fibrillation or ventricular tachycardia, heart failure, and weight loss in a patient with heart disease.

Red flags.

• Recurrent arrhythmia, falling ejection fraction or heart failure.
• Fever, agitation, delirium or vomiting (thyroid storm).

• Suppressed thyroid stimulating hormone with raised free thyroxine and free triiodothyronine. Free triiodothyronine may be disproportionately low in type 2 because amiodarone blocks conversion.
• Thyrotropin receptor antibodies and thyroid peroxidase antibodies (positive favours type 1).
• Colour flow Doppler ultrasound: normal or increased flow and a nodular or diffuse goitre in type 1; absent flow in type 2.
• Radioiodine or technetium uptake: very low in type 2, and low, normal or high in type 1. Interleukin-6 and ESR are raised in type 2.
• Mixed forms are common, and the distinction is often unclear.

Differential diagnosis.

• Graves disease and toxic nodular goitre not caused by amiodarone.
• Recurrence of the arrhythmia from another cause.
• Painless thyroiditis from another drug and non-thyroidal illness.

• Cardiology review. Stopping amiodarone rarely shortens the illness because of its long half life, and arrhythmia control takes priority. Stop it only if another antiarrhythmic is safe.
• Beta blocker: propranolol 10 to 40 mg three to four times daily. Watch for additive bradycardia and conduction block.
• Type 1: carbimazole 40 mg daily (up to 60 mg), responding slowly. Potassium perchlorate 200 mg four times daily for up to 4 weeks (not over 1 g daily) can be added, with blood count checks for agranulocytosis and aplastic anaemia.
• Type 2: prednisolone 30 to 40 mg daily for 2 to 4 weeks, then reduce over 2 to 3 months.
• Mixed or uncertain type: carbimazole plus prednisolone, then adjust to response.
• Urgent thyroidectomy for refractory disease, severe heart failure or arrhythmia, in a centre with experience of high risk anaesthesia. Plasma exchange can prepare a patient for surgery.
• Hypothyroidism after type 2 is common: treat with levothyroxine (about 1.6 micrograms/kg daily; start 25 to 50 micrograms in older adults or heart disease).

Special groups. Pregnancy: amiodarone is avoided because of foetal goitre and hypothyroidism. Thyroid function in the neonate needs review.

Monitoring. Free thyroxine and thyroid stimulating hormone every 4 weeks until stable, then every 6 to 8 weeks. Thyroid stimulating hormone can stay suppressed for weeks after recovery. Check an electrocardiogram and ejection fraction.

Referral and escalation. Endocrinology and cardiology together for every case; surgery referral for refractory disease.