Amiodarone and thyroid dysfunction

Amiodarone and thyroid dysfunction

Abstract: Amiodarone causes thyroid dysfunction by virtue of the high iodine content. Hypothyroidism occurs in iodine sufficient areas and hyperthyroidism occurs in iodine deficient areas.

Amiodarone is one of the most widely used anti arrhythmic drug. It is well known that amiodarone can induce both hypothyroidism and hyperthyroidism due to the iodine content of the drug. 200 milligrams of amiodarone daily would deliver twenty to forty times the usual daily iodine intake. Amiodarone reduces 5-deiodinase activity and thereby the mono deiodination of T4 to T3. There is decreased generation of T3 and reduced clearance of rT3 (reverse T3), which accumulates. Destructive thyroiditis is due to the direct toxic effect of amiodarone and its metabolite on the thyroid follicular cells.¹

It has been mentioned that during amiodarone treatment, hypothyroidism occurs in iodine sufficient areas and hyperthyroidism occurs in iodine deficient areas.² Screening for pre-existing thyroid disease and thyroid function prior to initiating amiodarone are ideal in cases where the drug is being started on an elective basis. Thyroid scan results may not be interpretable once a significant dose of iodine in the form of amiodarone has been delivered into the system, especially after an initial intravenous initiation of therapy in life threatening situations. Periodic follow up with thyroid function tests are also recommended while on long term amiodarone therapy. Thyroid stimulating hormone (TSH) level is one of the earliest to rise with amiodarone and can occur as early as 48 hours, reaching nearly three times the normal levels by 10th day.

Amiodarone induced thyrotoxicosis

Amiodarone induced hyperthyroidism is less common than hypothyroidism. Amiodarone induced hyperthyroidism (thyrotoxicosis) has been classified into two types:³

1. Type I due to excessive iodine induced synthesis of thyroid hormone
2. Type II is due to amiodarone induced destructive thyroiditis

Type I amiodarone induced hyperthyroidism can be treated with withdrawal of amiodarone if the clinical condition permits. It may be noted that due to the long half life of amiodarone, stopping of the drug may not bring any immediate relief of hyperthyroidism. Moreover there can even be an initial worsening as amiodarone blocks peripheral conversion of T4 to T3. Very often, the clinical condition may not permit withdrawal of amiodarone as it is often used for life threatening cardiac arrhythmias.
If withdrawal of amiodarone is not an option, treatment with thioamide drugs like Carbimazole, Methimazole or Propylthiouracil may be needed. Higher doses of these drugs may be needed due to the high iodine levels in the body. Though Propylthiouracil was initially preferred for amiodarone induced thyrotoxicosis as it reduces peripheral deiodinase activity, a safety warning has been issued due to its potential liver toxicity.

Amiodarone induced thyroiditis (type II amiodarone induced thyrotoxicosis) may be treated with corticosteroids. Antithyroid drugs may be needed in certain cases. Some of these cases of amiodarone induced thyroiditis with hyperthyroidism may eventually become hypothyroid.
Other therapeutic measures like thyroidectomy, plasmapheresis, lithium, and radioiodine ablation of thyroid, are reserved for refractory cases of amiodarone induced thyrotoxicosis and seldom needed.

Amiodarone induced hypothyroidism

Amiodarone versus Sotalol for Atrial Fibrillation trial (SAFE-T) sub study involving more than 612 patients, documented subclinical hypothyroidism with TSH levels between 4.5-10 mU/L in 25.8% of those treated with amiodarone.⁴ TSH levels above 10 mU/L were noted in 5%. In older males, hypothyroidism developed in about 30.8% of cases. Permanent hypothyroidism is likely to occur in those with thyroid antibodies indicating thyroiditis.

Amiodarone induced hypothyroidism can be treated with levothyroxine supplementation if the clinical condition does not permit withdrawal of amiodarone. Those without pre-existing thyroid disease may become euthyroid within two to four months of stopping amiodarone in clinically permissible situations.

References

1. Narayana SK, Woods DR, Boos CJ. Management of Amiodarone-Related Thyroid Problems. Therapeutic Advances in Endocrinology and Metabolism 2011;2(3):115-126.
2. Basaria S, Cooper DS. Amiodarone and the thyroid. Am J Med. 2005 Jul;118(7):706-14.
3. Padmanabhan H. Amiodarone and thyroid dysfunction. South Med J. 2010 Sep;103(9):922-30.
4. Elizabeth L Batcher, X Charlene Tang, Bramah N Singh, Steven N Singh, Domenic J Reda, Jerome M Hershman, SAFE-T Investigators. Thyroid function abnormalities during amiodarone therapy for persistent atrial fibrillation. Am J Med. 2007 Oct;120(10):880-5.