Amiodarone Thyroid Toxicity

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  •  Overview:
    • Iodine-rich compound with some structural similarity to thyroxine (T4)
    • Standard maintenance therapy with 200 mg amiodarone can provide more than 100 times the daily iodine requirement
    • Elimination half-life of amiodarone is highly variable, ranging from 50-100 days
    • Total body iodine stores remain increased for up to 9 months after discontinuation
  • Usual Effect of Amiodarone on Thyroid hormone levels
    • Serum T4 levels rise by 20-40% during the first month of therapy and then gradually fall toward high normal.
    • Serum T3 levels decrease by up to 30% within the first few weeks of therapy and remain slightly decreased or low normal.
    • TSH levels usually rise after the start of therapy but return to normal in 2-3 months. NOT an indication for T4 replacement.
  • Amiodarone Toxicity: can cause both hyperthyroidism and hypothyroidism
    • Thyrotoxicosis:
      • Type 1 usually affects patients with latent or preexisting thyroid disorders and is more common in areas of low iodine intake. Caused by iodine-induced excess thyroid hormone synthesis and release (Jod-Basedow phenomenon).
      • Type 2 occurs in patients with a previously normal thyroid gland and is caused by a destructive thyroiditis that leads to the release of preformed thyroid hormones.
    • Hypothyroidism: due to enhanced susceptibility to the inhibitory effect of iodine on thyroid hormone synthesis (Wolff-Chaikoff effect), combined with the inability to escape from this effect after an iodine load in patients with preexisting Hashimoto thyroiditis.
  • Diagnosis
    • Hyperthyroidism:
      • Elevated T4, elevated T3, undetectable TSH; (also commonly seen in the early phases of amiodarone therapy)
      • Check T3: T3 levels are increased in hyperthyroidism, while they are decreased in early phases of treatment with amiodarone.
      • Thyroid autoantibodies are generally absent in type 2 AIT. Autoantibodies supports the diagnosis of type 1 AIT.
      • An ultrasonogram of the thyroid that shows abnormalities such as hypoechoic or nodular patterns or increased gland size is more indicative of type 1
    • Hypothyroidism:
      • Similar to those for spontaneous hypothyroidism and include decreased levels of serum free T4 and increased levels of serum TSH
  • Treatment:
    • Stop amiodarone?
      • Continuation of amiodarone treatment does not alter the basic approach to the medical management of thyrotoxicosis, but it reduces the chances of a successful outcome.
      • Even if amiodarone therapy is stopped, thyrotoxicosis persists for up to 8 months because of the drug’s long half-life. Discontinuation of the drug has no immediate benefit.
      • Amiodarone therapy is usually continued unless it is ineffective in treating the arrhythmia or toxicity in other organs is evident.
    • Hyperthyroidism
      • Type 1 Thyrotoxicosis: high doses of thionamides (eg, methimazole [40-60 mg/d] or propylthiouracil [600-800 mg/d]
      • Type 2 Thyrotoxicosis: relatively long course of glucocorticoids (start at 40mg and taper over months, until T4 normalizes).
      • Unknown , type 1 v 2: combination of glucocorticoids and thionamides.
        • A rapid response suggests type 2 AIT; thionamides can be tapered.
        • A poor initial response suggests type 1 AIT; the steroids can be tapered.
      • RAIU?: not a great choice, as the iodine of amiodarone inhibits uptake by the gland
      • Thyroidectomy: can be considered for type 1 thyrotoxicosis, but only after the euthyroid state is established and if there is a need to restart amiodarone
    • Hypothyroidism
      • No preexisting thyroid disease: often resolves after discontinuation of amiodarone
      • Underlying thyroid disease: may require permanent T4 replacement therapy. Amiodarone therapy is usually continued while T4 is used to normalize the TSH level.