THE DEIODINATION OF THYROXINE IN HYPERTHYROID RATS AS DETERMINED BY RENAL CLEARANCE OF IODIDE

Abstract

ABSTRACT Other investigators have reported that whole body clearance of thyroxine (T4) is increased in hyperthyroid rats isotopically equilibrated with radioactive T4, using the 24 h post-injection serum T4 concentration in the clearance calculation. Data from this laboratory indicate that serum T4 concentration is lowest at this point yielding falsely high clearance values, particularly when high doses of T4 are injected. To investigate this problem further, two types of experiments were performed. First, rats were equilibrated with [125I]T4, 5 or 20 μg/day, and the urinary clearance of iodide derived from T4 (deiodinative clearance) was measured from 0–7 and 7–24 h after a T4 injection, using the T4 concentration in serum obtained at the midpoint of each urine collection period. Urine was then collected from the ureters for several 1 h periods during the 4th to 8th h following T4 injection, calculating clearances using the midpoint plasma T4 concentration. Second, normal rats were given a single dose of [125I]T4, 5 or 55 μg/rat, and deiodinative clearance was determined during the subsequent 0–7 and 7–24 h periods. The first experiment indicated that deiodinative clearance was significantly enhanced in rats equilibrated with the large dose of T4 under all conditions studied. In contrast, the clearance in normal rats given a single large dose of T4 was not significantly different from that of normal rats given a small dose of T4. These results support the view that T4 clearance is increased in hyperthyroidism, due in part to an increase in the deiodination of T4.