Are selective increases in serum thyroxine (t4)due to iodinated inhibitors of t4 monodeiodination indicative of hyperthyroidism?

Abstract

The term “T4 toxicosis” has been used to describe the selective increase in serum total and free T4 that has been noted in some patients during acute or chronic nonthyroidal illness. However, this term implies that the production rate (PR) of T4 in these patients is similar to that observed in patients with classical hyperthyroidism. Since it is unknown whether this situation pertains, we have performed measurements of the T4 MCR and PR in five such patients. Four of these subjects were being treated with amiodarone, an antiarrhythmic agent that also inhibits T4monodeiodination, and one patient had received a radiocontrast dye (ioxithalamic acid). The MCR (15.4 ± 0.9 ml/day/kg, mean ± SEM) and the half-life of T4(7.3 ± 0.3 days) were in the euthyroid range. The T4 PR was increased (191 ± 20 nmol/day) when compared with normal subjects on no medication but was significantly lower than the T4 PR measured in five patients with classical hyper-thyroidism (478 ± 68 nmol/day P < 0.005). In (a separate series of experiments, T4 and T3 kinetics were measured ina group of normal subjects receiving amiodarone for 21 days. This agent increased the half-life ofT4 from 6.6 ± 0.2 to 8.1 ± 0.4 days (P < 0.001) and decreased the T4 MCR from 18.8 ± 1.0 to 14.1 ± 0.9 ml/day/kg. The kinetic parameters of T3 were not significantly altered by the drug. From these results we conclude the following: 1) the selective increase in serum T4 concentrations induced by amiodarone and ioxithalamic acid is mainly due to a reduction in the T4 MCR; 2) amiodarone also causes a decrease in serum (T)3 concentrations and in some patients results in a compensatory rise i n T4PR; 3) when there has been a recent history of the aministration of amiodarone, the diagnostic value of an increased serum total and free T4 is limited, and therefore the exclusive reliance upon these parameters may lead to an erroneous diagnosis of hyperthyroidism. © 1982 by The Endocrine Society.