Metabolic clearance and production rates of 3′, 5′-diiodothyronine in hyperthyroidism and hypothyroidism in man: Comparison of infusions using radiolabeled versus unlabeled iodothyronine

We have examined the MCR and production rate (PR) of 3′, 5′-diiodothyronine (3′, 5′-T₂) in states of altered thyroid function. Although the major thrust of these studies was to examine the metabolism of [¹²⁵I]3′, 5′-T₂ in hyperthyroid and hypothyroid subjects and in athyreotic patients receiving L-T₄ replacement, a second aspect of the study was to determine whether infusions of unlabeled 3′, 5′-T₂ yielded results comparable to those obtained by radiolabeled infusions. Serum 3′, 5′-T₂ concentrations(mean ± SE) were 8.4 ± 1.1 ng/dl in five hyperthyroid, 7.2 ± 0.4 ng⁄dl in five T₄-replaced, and less than 2.0 ng⁄ dl in five hypothyroid subjects. The MCRs (mean ± SE) determined by [¹²⁵I]3′, 5′-T₂ infusions differed significantly among groups and were 448 ± 23, 354 ± 23, and 251 ± 17 liters⁄70 kg day in the hyperthyroid, T₄-replaced, and hypothyroid groups, respectively. When infusions were performed in the same patients using unlabeled 3′, 5′-T₂, the results were 463 ± 29, 360 ± 21, and 245 ± 8 liters/70 kg day. The PRs using the isotopic and unlabeled infusion techniques were 38.0 ± 5.5 vs. 39.0 ± 6.6 μg/ 70 kg-day in the hyperthyroid, 25.4 ± 3.3 vs. 26.4 ±2.9 μg/70 kg day in the T₄-replaced, and 3.1 ± 0.6 vs. 3.0 ± 0.6 jug/70 kg·day in the hypothyroid groups. In four euthyroid subjects receiving infusions only of unlabeled hormone the MCR was 276 ± 34 liters/70 kg·day and the PR was 16.4 ± 2.2 μg/70 kg-day. While the free 3′, 5′-T₂ levels were significantly higher in the hyperthyroid than in the hypothyroid groups (83 ± 16 vs. 17 ± 2 pg/dl), the dialyzable fraction of 3′, 5′-T₂ was similar in all three groups. Infusions of unlabeled 3′, 5′-T₂ produced up to 100-fold increases in total and free 3′, 5′-T₂ yet there were no changes in the dialyzable fraction. Although not significantly different, the mean serum total and free 3′-monoiodothyronine (3′-T₁) concentrations were greater in the hyperthyroid subjects than in the other two groups. The molar total 3′-T₁ to 3′, 5′-T₂ ratio was greater in the hyperthyroid (0.56 ± 0.08) than in the T₄-replaced (0.24± 0.03) or hypothyroid (0.20 ± 0.03) groups. These results indicate that the MCR and PR of 3′, 5′-T₂ vary directly with the thyroid state and that 3′, 5′-T₂ is a significant product of thyroid hormone metabolism; they suggest that peripheral 5′-deiodination of 3′, 5′-T₂ to 3′-T₁ is enhanced in hyperthyroid subjects. Moreover, the high correlation between MCRs (r < 0.89; P = 0.001) and PRs (r = 0.98; P < 0.001) using radiolabeled vs. unlabeled 3′, 5′-T₂ infusions strongly suggests that the latter technique is valid for kinetic studies of this (and perhaps other biologically inactive) iodothyronines.