Thyroid Dysfunction Induced by Amiodarone Therapy Clinical Presentation

Updated: Mar 28, 2017
  • Author: Mini Gopalan, MD; Chief Editor: Romesh Khardori, MD, PhD, FACP  more...
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Presentation

History

The clinical presentation of AIH is usually subtle, while that of AIT can be dramatic, with life-threatening cardiac manifestations without antecedent subclinical biochemical findings. Suspect AIT in a patient who was previously stable while receiving amiodarone but who starts to show signs of cardiac decompensation, tachyarrhythmias, or angina. However, patients may lack cardiac manifestations because of amiodarone's intrinsic effect on the heart, and other signs of hyperthyroidism such as weight loss and fatigue may predominate. Thyrotoxicosis can occur while a patient receives amiodarone and even several months after discontinuation of treatment. Hypothyroidism is rare after the first 18 months of therapy.

  • Symptoms of AIT include the following:
    • Unexplained weight loss
    • Heat intolerance or increased perspiration
    • Profound muscle weakness
    • Unexplained fatigue
    • Emotional lability
    • Frequent stools
    • Oligomenorrhea
    • Anxiety, nervousness, or palpitations
  • Symptoms of AIH include the following:
    • Fatigue
    • Lethargy
    • Cold intolerance
    • Mental sluggishness
    • Weakness
    • Constipation
    • Menorrhagia
    • Dry skin
  • A family history of certain conditions can also be important. Consider the following:
    • Autoimmune disease
    • Thyroid disease
    • Medication history
    • Emigration from iodine-deficient areas
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Physical

The physical signs of thyrotoxicosis or hypothyroidism induced by amiodarone therapy do not differ from those observed in states of thyroid excess or deficiency attributable to other causes.

  • Signs of AIT include tremor, goiter, heart failure, sinus tachycardia, and atrial fibrillation.
  • The presence of proptosis or multinodular or diffuse goiter usually indicates type 1 AIT. A small, often tender, goiter occasionally develops in patients with type 2 AIT.
  • The clinical manifestations of AIH are similar to those of spontaneous hypothyroidism. Patients present with vague symptoms and signs such as fatigue, lethargy, cold intolerance, mental sluggishness, and dry skin. A goiter is found in 20% of patients with hypothyroidism who live in iodine-replete areas, but most of these goiters predate the start of amiodarone treatment. Myxedema coma has also been reported in a patient receiving long-term amiodarone therapy. In patients already receiving levothyroxine replacement therapy, the dose of levothyroxine may need to be increased to offset the amiodarone-induced inhibition of the T4-to-T3 conversion.
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Causes

The risk of developing hypothyroidism or thyrotoxicosis is independent of the daily or cumulative dose of amiodarone. However, some small studies show the contrary. Autoimmune thyroid disease is the principal risk factor for the development of hypothyroidism. High dietary intake and a positive family history of thyroid disease may also be predisposing factors. Females with thyroid peroxidase or thyroglobulin antibodies have a relative risk of 13.5% for the development of hypothyroidism.

A Japanese study, by Kinoshita et al, indicated that in patients receiving amiodarone, the presence of dilated cardiomyopathy and cardiac sarcoidosis are risk factors for amiodarone-induced hyperthyroidism, while higher baseline TSH levels and lower baseline free thyroxine levels are predictors for amiodarone-induced hypothyroidism. The investigators also stated that because the TSH and free thyroxine levels are apparent risk factors, subclinical hypothyroidism may be a predictor for amiodarone-induced hypothyroidism. [7]

A literature review by Zhong et al indicated that new-onset AIH is particularly likely to occur in older women and in regions with a high environmental iodine content. The incidence of AIH in women was reported to be 19.2%, compared with 13.3% in men, with mean age found to correlate positively with the percentage of women. In areas with a high iodine content, the incidence of AIH was 20.3%, compared with 8.7% in regions with a low iodine content. [8]

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