Amiodarone alters thyroxine transfer and distribution in humans

Previous studies indicate that increased serum total and free T 4 levels may be secondary to a proportionally greater decrease in serum T 4 clearance rates than in production rates after short-term amiodarone administration, to increased T 4 production rates as well as reduced serum clearance rates in selective hyperthyroxinemia without overt hyperthyroidism following chronic amiodarone administration, and to a relatively greater increase in T 4 production rates than in clearance rates in classical hyperthyroidism. To further evaluate amiodarone-induced alterations of T 4 metabolism, serum T 4 transfer and distribution were evaluated by compartmental analysis of T 4 kinetic studies from eight normal subjects receiving short-term amiodarone or an equivalent amount of iodide, five patients with selective hyperthyroxinemia induced by chronic amiodarone therapy (n = 4) or ioxithalamic acid (n = 1), and five with classical hyperthyroidism. The model consisted of rapidly and slowly equilibrating pools exchanging with serum, with all losses occurring from the tissue pools. Short-term amiodarone administration reduced the fractional T 4 transfer rates between serum and the rapidly equilibrating pool to 82% of baseline. In selective hyperthyroxinemia the fractional rates of T 4 transfer between serum and both extravascular pools were increased sixfold, whereas minimal alterations were present in the hyperthyroid group. The serum equivalent volume of T 4 distribution in the slow pool was significantly reduced following short-term amiodarone, whereas serum and rapid pool volumes were reduced in selective hyperthyroxinemia and slow pool volume was increased in hyperthyroidism. The total mean residence times were increased in the serum and rapid pools following short-term amiodarone, increased in the slow pool in selective hyperthyroxinemia, and decreased in the serum pool with hyperthyroidism. The single-pass mean transit times were increased in the serum and rapid pools after short-term amiodarone, reduced in all three pools with selective hyperthyroxinemia, and reduced only in the rapid pool in the hyperthyroid patients. The reduced bidirectional fractional transfer rates of T 4 between serum and rapidly equilibrating tissues after short-term amiodarone administration may be secondary to amiodarone-induced inhibition of the T 4 transfer process. The decreased serum clearance and disappearance rates may be related to an inhibitory effect of amiodarone on the T 4 degr