Metabolism of phenolic- and tyrosyl-ring labeled l-thyroxine in human beings and rats

The metabolism of L-thyroxine (T₄) labeled with radioiodine in the phenolic (T₄-3',5'-¹³¹I) and tyrosyl (T₄-3,5-¹²⁵I) rings was studied simultaneously both in human subjects and groups of rats. A similar study was carried out using T₄ labeled uniformly with ¹⁴C in the tyrosyl ring (T₄-tyr-¹⁴C) in one group of rats. No significant differences in the plasma fractional disappearance rate, total distribution volume, or in the metabolic clearance rate were observed between the 2 radioiodinated T₄ preparations in either the human subjects or rats. The daily and cumulative urinary excretion of radioiodine derived from either ring was the same in the human subjects whereas the urinary excretion rate of phenolic ring iodine slightly exceeded the tyrosyl ring iodine in the rat. Since, in the same rats, no corresponding decrease in the fecal excretion of phenolic ring iodine or any systematic differences in plasma values between the 2 isotopes occurred, the small increase in urinary phenolic iodine was attributed to an undefined methodologic error. The plasma fractional disappearance rate of T₄-tyr-¹⁴C was constant after 4-6 hr and similar to that of the iodine labeled T₄ preparations. The daily and cumulative excreted radioactivity (¹⁴C) (urine plus feces) was comparable to the iodine isotopes of T₄. Thus, these data show a rapid excretion of all portions of the T₄ molecule relative to the t_1/2 of T₄ and indicate that no large quantities of long-lived intermediates of T₄ are formed. Moreover, they suggest that iodine atoms from both rings are removed at the same rate and raise the possibility that during T₄ metabolism iodine atoms are removed in random fashion from either ring.