Effects of amiodarone on thyroid iodine metabolism in vitro

Since alterations of thyroid function have been reported in patients treated with amiodarone, 2-butyl,3-(4-diethylaminoethoxy-3,4-diiodo, benzoyl) benzufuran, the effects of this drug on the active iodide transport, organic iodine formation, thyroid peroxidase and the enzymatic iodotyrosine deiodination, were studied. In pig thyroid slices the iodide transport was affected by amiodarone at concentrations of 10(-4) M and 10(-5) M, showing a decrease of T/M (tissue/medium) ratios of 20% and 23%, respectively. Lower concentrations produced no significant differences from the controls. Iodotyrosine synthesis was only, but poorly, affected by 10(-4) M and 10(-5) M amiodarone. Inhibition of the DIT formation was greater than that produced for MIT. Thyroid peroxidase activity, as measured by the tyrosine-iodinase assay, showed a 20% decrease at 10(-3) M amiodarone. None of the other concentrations have affected the activity of the enzyme, except for 7% at a concentrations of 10(-4) M. The iodotyrosine deiodination was affected by amiodarone only at a concentration of 10(-3) M and 10(-4) M. The inhibitions were of 22.5% and 16.8%, respectively. We have concluded that, under the conditions of our study, amiodarone per se does not affect the intrathyroidal iodine metabolism in concentrations which are usually present in the sera of patients treated with this drug. However, it is not possible to rule out an in vivo direct action, if amiodarone is substantially concentrated in the human thyroid gland.