Amiodarone-induced thyrotoxicosis. A review.
Amiodarone (AM), a potent class III anti-arrhythmic drug, is an iodine-rich compound with a structural resemblance to thyroid hormones triiodothyronine (T3) and thyroxine (T4). At the commonly employed doses, AM causes iodine overload up to 50-100 times the optimal daily intake, which may be responsible of a spectrum of effects on thyroid function often counterbalancing its heart benefits. Although most patients on chronic AM treatment remain euthyroid, a consistent proportion may develop thyrotoxicosis (AM-induced thyrotoxicosis, AIT) or hypothyroidism. AIT is more prevalent in iodine-deficient areas and is currently subdivided in two different clinico-pathological forms (AIT I and AIT II). AIT I develops in subjects with underlying thyroid disease, and is caused by an exacerbation by iodine load of thyroid autonomous function; AIT II occurs in patients with no underlying thyroid disease and is probably consequent to a drug-induced destructive thyroiditis. Mixed or indeterminate forms of AIT encompassing several features of both AIT I and AIT II may be also observed. The differential diagnosis between AIT I and AIT II (which is important for the choice of the appropriate therapy) is currently made on radioiodine uptake (RAIU), which may be high, normal or low but detectable in AIT I, while is consistently very low or undetectable in AIT II and on colour-flow Doppler sonography (CFDS) showing normal or increased vascularity in AIT I and absent vascularity in AIT II. Quite recently, studies carried out in our Units at the University of Cagliari (Italy) showed that sestaMIBI thyroid scintigraphy may represent the best single test to differentiate AIT I (showing increased MIBI retention) from AIT II (displaying no significant uptake). Treatment of AIT is dependent from its etiology. AIT usually responds to combined thionamides and potassium perchlorate (KClO4) therapy, AIT II generally responds to glucocorticoids, while indeterminate forms may require both therapeutic approaches. In patients with AIT I definitive treatment of hyperthyroidism by administration of (131)I, initially not feasible for the low RAIU and/or the risk of thyrotoxicosis exacerbation, is advised after normalization of iodine overload. To control severe AIT additional treatment with lithium carbonate, the use of short course of iopanoic acid and plasmapheresis have been also proposed. In cases resistant to medical treatment and/or in patients with severe cardiac diseases who cannot interrupt AM or require quick AM reintroduction, total thyroidectomy (possibly carried out by minimally invasive video-assisted technique) may be proposed after rapid correction of thyrotoxicosis with combination of thionamides, KClO4, corticosteroids and a short course of iopanoic acid.
Department of Nuclear Medicine and Endocrinology, University Policlinic, University of Cagliari, Cagliari, Italy. pigam@medicina.unica.it
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D000638:Amiodarone / Q000009:adverse effects*; D000889:Anti-Arrhythmia Agents / Q000009:adverse effects*; D006801:Humans; D015850:Interleukin-6 / Q000097:blood; D007455:Iodine / Q000009:adverse effects / Q000172:deficiency; D007457:Iodine Radioisotopes / Q000627:therapeutic use; D007480:Iopanoic Acid / Q000627:therapeutic use; D016651:Lithium Carbonate / Q000627:therapeutic use; D010472:Perchlorates / Q000627:therapeutic use; D010956:Plasmapheresis; D017680:Potassium Compounds / Q000627:therapeutic use; D017256:Technetium Tc 99m Sestamibi; D013959:Thyroid Diseases / Q000150:complications; D013965:Thyroidectomy; D013971:Thyrotoxicosis / Q000139:chemically induced* / Q000145:classification / Q000175:diagnosis / Q000000981:diagnostic imaging / Q000188:drug therapy / Q000601:surgery; D018615:Ultrasonography, Doppler, Color
D000889:Anti-Arrhythmia Agents; C508600:IL6 protein, human; D015850:Interleukin-6; D007457:Iodine Radioisotopes; D010472:Perchlorates; D017680:Potassium Compounds; D016651:Lithium Carbonate; C009006:potassium perchlorate; D007455:Iodine; D017256:Technetium Tc 99m Sestamibi; D007480:Iopanoic Acid; D000638:Amiodarone