title: Does a hidden pool of reverse triiodothyronine (rT3) production contribute to total thyroxine (T4) disposal in high T4 states in man.
abstract: A hidden pool of rT3 production represents a source of rT3 that is minimally reflected in circulating rT3 levels. To test for the existence of such a source of rT3 production in man, varying doses of the generalized deiodinase inhibitor iopanoic acid (IA) were administered to four hyperthyroxinemic subjects. The doses employed included low-IA (0.5-g load, then 0.5 g/day for 5 days), mid-IA (1.0-g load, then 1.0 g/day for 5 days), and high-IA (3.0-g load, then 3.0 g/day for 5 days). Each patient received 25 microCi [125I]rT3, iv, in the high T4 state and on day 3 of each IA dosing regimen. Serial blood and urine samples were obtained to determine serum rT3 clearance rates and the urinary thyronine metabolite patterns. Although total serum rT3 values were increased by all IA dosages (P less than 0.001), rT3 was lower with high-IA administration (P less than 0.02) than with low- or mid-IA regimens. Low-IA decreased rT3 clearance to 33 +/- 2 L/day (P less than 0.005), while increasing the daily rT3 production to 76 +/- 8 nmol/day (P less than 0.04) compared to the control values (150 +/- 10 L/day and 53 +/- 8 nmol/day, respectively). Mid-IA also reduced rT3 clearance (23 +/- 4 L/day; P less than 0.005) without changing rT3 production (50 +/- 10 nmol/day), while high-IA reduced both rT3 clearance (21 +/- 2 L/day; P less than 0.005) and production (39 +/- 9 nmol/day; P less than 0.04). Intravenously administered tracer rT3 could not be detected in the urine in the high T4 state, but rT3 could not be detected in the urine in the high T4 state, but was prominent after IA administration. It is concluded that a hidden pool of rT3 production exists in vivo in man. Further, low dose IA serves as a selective inhibitor of liver and kidney deiodinase systems, allowing reflection of this hidden rT3 pool in the blood and urine. It would appear that hypertrophy of this hidden pool of rT3 production occurs in high T4 states and may account for the majority of the unrecognized deiodinative metabolites of T4 generated in hyperthyroxinemia.
authors.affiliation: Department of Medicine, University of Southern California School of Medicine, Los Angeles 90033.
authors.forename: J S
authors.initials: JS
authors.lastname: LoPresti
authors.forename: K P
authors.initials: KP
authors.lastname: Anderson
authors.forename: J T
authors.initials: JT
authors.lastname: Nicoloff
mesh_terms: D000328:Adult; D004305:Dose-Response Relationship, Drug; D006801:Humans; D006980:Hyperthyroidism / Q000201:enzymology / Q000378:metabolism*; D007275:Injections, Intravenous; D007453:Iodide Peroxidase / Q000037:antagonists & inhibitors / Q000378:metabolism*; D007480:Iopanoic Acid / Q000008:administration & dosage; D007668:Kidney / Q000201:enzymology; D008099:Liver / Q000201:enzymology; D008297:Male; D008875:Middle Aged; D013960:Thyroid Function Tests; D013974:Thyroxine / Q000008:administration & dosage / Q000378:metabolism*; D014284:Triiodothyronine / Q000096:biosynthesis* / Q000502:physiology
chemical_list: D014284:Triiodothyronine; D007453:Iodide Peroxidase; D007480:Iopanoic Acid; D013974:Thyroxine