Thyroxine metabolism in the rat: effect of varying doses of exogenous thyroxine.

Experiments were performed to determine quantitatively the peripheral metabolism of exogenous thyroxine (T4) in rats brought to isotopic equilibrium with doses of -131I-T4 ranging from 1 to 20 mug/100 g body weight/day. It was found that, although the absolute amount of T4 either deiodinated and excreted as iodide in urine or excreted as T4 in faeces increased as the dose of T4 increased, the percentage of hormone excreted by either pathway at each dose level was relatively constant. In other words, the fractional rate of deiodination is not greatly influenced by the amount of T4 administered. A 20-fold increase in the dose of T4 resulted in only a 4-fold increase in serum T4 concentration measured 24 h after injection, but serum T4 levels were elevated considerably more than this for several hours between injections. Nevertheless, the highest dose of T4 was not greatly thyrotoxic. The implications of these findings in relation to the possible association between the metabolism and action of T4 are discussed.