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

Robert Christian Smallridge, K. D. Burman, C. E. Smith, K. R. Latham, F. D. Wright, L. Wartofsky

Research output: Contribution to journalArticle

7 Citations (Scopus)

Abstract

We have examined the MRC and production rate (PR) of 3',5'-diiodothyronine (3',5'-T 2) in states of altered thyroid function. Although the major thrust of these studies was to examine the metabolism of [ 125I]3',5'-T 2 in hyperthyroid and hypothyroid subjects and in athyreotic patients receiving L-T 4 replacement, a second aspect of the study was to determine whether infusions of unlabeled 3',5'-T 2 yielded results comparable to those obtained by radiolabeled infusions. Serum 3',5'-T 2 concentrations (mean ± SE) were 8.4 ± 1.1 ng/dl in five hyperthyroid, 7.2 ± 0.4 ng/dl in five T 4-replaced, and less than 2.0 ng/dl in five hypothyroid subjects. The MCRs (mean ± SE) determined by [ 125I]3',5'-T 2 infusions differed significantly among groups and were 448 ± 23, 354 ± 23, and 251 ± 17 liters/70 kg.day in the hyperthyroid, T 4-replaced, and hypothyroid groups, respectively. When infusions were performed in the same patients using unlabeled 3',5'-T 2, 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 T 4-replaced, and 3.1 ± 0.6 vs. 3.0 ± 0.6 μg/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'-T 2 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'-T 2 was similar in all three groups. Infusions of unlabeled 3',5'-T 2 produced up to 100-fold increases in total and free 3',5'-T 2, yet there were no changes in the dialyzable fraction. Although not significantly different, the mean serum total and free 3'-monoiodothyronine (3'-T 1) concentrations were greater in the hyperthyroid subjects than in the other two groups. The molar total 3'-T 1 to 3',5'-T 2 ratio was greater in the hyperthyroid (0.56 ± 0.08) than in the T 4-replaced (0.24 ± 0.03) or hypothyroid (0.20 ± 0.03) groups. These results indicate that the MCR and PR of 3',5'-T 2 vary directly with the thyroid state and that 3',5'-T 2 is a significant product of thyroid hormone metabolism; they suggest that peripheral 5'-deiodination of 3',5'-T 2 to 3'-T 1 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'-T 2 infusions strongly suggests that the latter technique is valid for kinetic studies of this (and perhaps other biologically inactive) iodothyronines.

Original languageEnglish (US)
Pages (from-to)722-730
Number of pages9
JournalJournal of Clinical Endocrinology and Metabolism
Volume52
Issue number4
StatePublished - 1981
Externally publishedYes

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Metabolic Clearance Rate
Hyperthyroidism
Hypothyroidism
Metabolism
Thyroid Hormones
Hormones
Thyroid Gland
Kinetics
3',5'-diiodothyronine
Serum

ASJC Scopus subject areas

  • Biochemistry
  • Endocrinology, Diabetes and Metabolism

Cite this

@article{43348bc6b67c4b0bb3e5f4f1e7b22b4b,
title = "Metabolic clearance and production rates of 3',5'-diiodothyronine in hyperthyroidism and hypothyroidism in man: Comparison of infusions using radiolabeled versus unlabeled iodothyronine",
abstract = "We have examined the MRC and production rate (PR) of 3',5'-diiodothyronine (3',5'-T 2) in states of altered thyroid function. Although the major thrust of these studies was to examine the metabolism of [ 125I]3',5'-T 2 in hyperthyroid and hypothyroid subjects and in athyreotic patients receiving L-T 4 replacement, a second aspect of the study was to determine whether infusions of unlabeled 3',5'-T 2 yielded results comparable to those obtained by radiolabeled infusions. Serum 3',5'-T 2 concentrations (mean ± SE) were 8.4 ± 1.1 ng/dl in five hyperthyroid, 7.2 ± 0.4 ng/dl in five T 4-replaced, and less than 2.0 ng/dl in five hypothyroid subjects. The MCRs (mean ± SE) determined by [ 125I]3',5'-T 2 infusions differed significantly among groups and were 448 ± 23, 354 ± 23, and 251 ± 17 liters/70 kg.day in the hyperthyroid, T 4-replaced, and hypothyroid groups, respectively. When infusions were performed in the same patients using unlabeled 3',5'-T 2, 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 T 4-replaced, and 3.1 ± 0.6 vs. 3.0 ± 0.6 μg/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'-T 2 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'-T 2 was similar in all three groups. Infusions of unlabeled 3',5'-T 2 produced up to 100-fold increases in total and free 3',5'-T 2, yet there were no changes in the dialyzable fraction. Although not significantly different, the mean serum total and free 3'-monoiodothyronine (3'-T 1) concentrations were greater in the hyperthyroid subjects than in the other two groups. The molar total 3'-T 1 to 3',5'-T 2 ratio was greater in the hyperthyroid (0.56 ± 0.08) than in the T 4-replaced (0.24 ± 0.03) or hypothyroid (0.20 ± 0.03) groups. These results indicate that the MCR and PR of 3',5'-T 2 vary directly with the thyroid state and that 3',5'-T 2 is a significant product of thyroid hormone metabolism; they suggest that peripheral 5'-deiodination of 3',5'-T 2 to 3'-T 1 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'-T 2 infusions strongly suggests that the latter technique is valid for kinetic studies of this (and perhaps other biologically inactive) iodothyronines.",
author = "Smallridge, {Robert Christian} and Burman, {K. D.} and Smith, {C. E.} and Latham, {K. R.} and Wright, {F. D.} and L. Wartofsky",
year = "1981",
language = "English (US)",
volume = "52",
pages = "722--730",
journal = "Journal of Clinical Endocrinology and Metabolism",
issn = "0021-972X",
publisher = "The Endocrine Society",
number = "4",

}

TY - JOUR

T1 - Metabolic clearance and production rates of 3',5'-diiodothyronine in hyperthyroidism and hypothyroidism in man

T2 - Comparison of infusions using radiolabeled versus unlabeled iodothyronine

AU - Smallridge, Robert Christian

AU - Burman, K. D.

AU - Smith, C. E.

AU - Latham, K. R.

AU - Wright, F. D.

AU - Wartofsky, L.

PY - 1981

Y1 - 1981

N2 - We have examined the MRC and production rate (PR) of 3',5'-diiodothyronine (3',5'-T 2) in states of altered thyroid function. Although the major thrust of these studies was to examine the metabolism of [ 125I]3',5'-T 2 in hyperthyroid and hypothyroid subjects and in athyreotic patients receiving L-T 4 replacement, a second aspect of the study was to determine whether infusions of unlabeled 3',5'-T 2 yielded results comparable to those obtained by radiolabeled infusions. Serum 3',5'-T 2 concentrations (mean ± SE) were 8.4 ± 1.1 ng/dl in five hyperthyroid, 7.2 ± 0.4 ng/dl in five T 4-replaced, and less than 2.0 ng/dl in five hypothyroid subjects. The MCRs (mean ± SE) determined by [ 125I]3',5'-T 2 infusions differed significantly among groups and were 448 ± 23, 354 ± 23, and 251 ± 17 liters/70 kg.day in the hyperthyroid, T 4-replaced, and hypothyroid groups, respectively. When infusions were performed in the same patients using unlabeled 3',5'-T 2, 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 T 4-replaced, and 3.1 ± 0.6 vs. 3.0 ± 0.6 μg/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'-T 2 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'-T 2 was similar in all three groups. Infusions of unlabeled 3',5'-T 2 produced up to 100-fold increases in total and free 3',5'-T 2, yet there were no changes in the dialyzable fraction. Although not significantly different, the mean serum total and free 3'-monoiodothyronine (3'-T 1) concentrations were greater in the hyperthyroid subjects than in the other two groups. The molar total 3'-T 1 to 3',5'-T 2 ratio was greater in the hyperthyroid (0.56 ± 0.08) than in the T 4-replaced (0.24 ± 0.03) or hypothyroid (0.20 ± 0.03) groups. These results indicate that the MCR and PR of 3',5'-T 2 vary directly with the thyroid state and that 3',5'-T 2 is a significant product of thyroid hormone metabolism; they suggest that peripheral 5'-deiodination of 3',5'-T 2 to 3'-T 1 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'-T 2 infusions strongly suggests that the latter technique is valid for kinetic studies of this (and perhaps other biologically inactive) iodothyronines.

AB - We have examined the MRC and production rate (PR) of 3',5'-diiodothyronine (3',5'-T 2) in states of altered thyroid function. Although the major thrust of these studies was to examine the metabolism of [ 125I]3',5'-T 2 in hyperthyroid and hypothyroid subjects and in athyreotic patients receiving L-T 4 replacement, a second aspect of the study was to determine whether infusions of unlabeled 3',5'-T 2 yielded results comparable to those obtained by radiolabeled infusions. Serum 3',5'-T 2 concentrations (mean ± SE) were 8.4 ± 1.1 ng/dl in five hyperthyroid, 7.2 ± 0.4 ng/dl in five T 4-replaced, and less than 2.0 ng/dl in five hypothyroid subjects. The MCRs (mean ± SE) determined by [ 125I]3',5'-T 2 infusions differed significantly among groups and were 448 ± 23, 354 ± 23, and 251 ± 17 liters/70 kg.day in the hyperthyroid, T 4-replaced, and hypothyroid groups, respectively. When infusions were performed in the same patients using unlabeled 3',5'-T 2, 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 T 4-replaced, and 3.1 ± 0.6 vs. 3.0 ± 0.6 μg/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'-T 2 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'-T 2 was similar in all three groups. Infusions of unlabeled 3',5'-T 2 produced up to 100-fold increases in total and free 3',5'-T 2, yet there were no changes in the dialyzable fraction. Although not significantly different, the mean serum total and free 3'-monoiodothyronine (3'-T 1) concentrations were greater in the hyperthyroid subjects than in the other two groups. The molar total 3'-T 1 to 3',5'-T 2 ratio was greater in the hyperthyroid (0.56 ± 0.08) than in the T 4-replaced (0.24 ± 0.03) or hypothyroid (0.20 ± 0.03) groups. These results indicate that the MCR and PR of 3',5'-T 2 vary directly with the thyroid state and that 3',5'-T 2 is a significant product of thyroid hormone metabolism; they suggest that peripheral 5'-deiodination of 3',5'-T 2 to 3'-T 1 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'-T 2 infusions strongly suggests that the latter technique is valid for kinetic studies of this (and perhaps other biologically inactive) iodothyronines.

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