What percentage of patients will suffer the complications of amiodarone therapy, and how reversible are the eye, lung, and liver changes?

What percentage of patients will suffer the complications of amiodarone therapy, and how
reversible are the eye, lung, and liver changes? How do I assess thyroid function in someone on amiodarone therapy?

Amiodarone therapy is associated with a number of serious toxicities which primarily involve the lung, heart, liver or thyroid gland. The drug is also associated with a wide array of other side effects involving the skin, eye, gastrointestinal tract and neurologic system. Drug discontinuance rates with amiodarone are closely related to its daily dose. The table summarises the cumulative incidence of adverse reactions reported in two separate meta-analyses.

Eye, lung, and liver toxicity are all potentially reversible if amiodarone is discontinued early after the development of toxicity. However, cases of permanent blindness, death from liver failure and death from respiratory failure have been rarely reported with amiodarone.

There are no adequate predictors of pulmonary toxicity, and serial lung function studies are usually not helpful. Dose and duration of treatment are no guide to risk. Clinical suspicion must remain high, especially in the elderly or those with co-existent pulmonary disease.

Amiodarone has been implicated as a cause of both hyperthyroidism and hypothyroidism. Hypothyroidism is a predictable response to the iodide load presented by amiodarone. Two types of hyperthyroidism have been reported to occur with amiodarone. Type I amiodarone-induced hyperthyroidism occurs in patients with underlying thyroid disease such as Graves disease. The iodide load in these patients accelerates thyroid hormone synthesis. Type II amiodarone-induced hyperthyroidism
occurs in patients with normal thyroids. Hyperthyroidism results from a direct toxic effect of amiodarone causing a subacute destructive thyroiditis with release of preformed thyroid hormone. Patients receiving amiodarone should have thyroid function evaluated at periodic intervals. A low TSH is indicative of hyperthyroidism, but does not distinguish between Type 1 and Type 2 hyperthyroidism. Radioactive iodine uptake may be low normal or elevated in Type 1 hyperthyroidism but is very low or
absent in Type 2 hyperthyroidism. Interleukin-6 levels are normal or moderately increased in Type 1, but markedly increased in Type 2 amiodarone-induced hyperthyroidism. In addition, colour flow Doppler ultrasound shows an absence of vascularity in Type 2 amiodarone-induced hyperthyroidism.

Amiodarone-induced hypothyroidism is characterised by an elevated TSH. Treatment of amiodarone-induced hypothyroidism is indicated if the free T4 is low or low normal and the TSH is greater than 20 microIU/ml.

As a complication of therapy, hyperthyroidism is more common where dietary iodine intake is low, whilst the reverse is true in areas of high intake.4 In patients with hyperthyroidism in whom amiodarone therapy is still warranted, thought should be given to concomitant treatment with carbimazole.