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 t1/2 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.
ASJC Scopus subject areas
- Endocrinology, Diabetes and Metabolism
- Clinical Biochemistry
- Biochemistry, medical