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Research Article Free access | 10.1172/JCI107265

Effects of Replacement Doses of Sodium-L-Thyroxine on the Peripheral Metabolism of Thyroxine and Triiodothyronine in Man

Lewis E. Braverman, Apostolos Vagenakis, Patricia Downs, Angela E. Foster, Kenneth Sterling, and Sidney H. Ingbar

St. Elizabeth's Hospital, Boston 02135

Department of Medicine, Tufts Medical School, Boston 02111

Thorndike Memorial Laboratory and the Harvard Medical Service, Boston 02115

Boston City Hospital, Boston 02118

Department of Medicine, Harvard Medical School, Boston, Massachusetts 02115

Protein Research Laboratory, Bronx Veterans Administration Hospital, Bronx, New York 10468

Department of Medicine, Columbia University College of Physicians and Surgeons, New York 10027

Find articles by Braverman, L. in: PubMed | Google Scholar

St. Elizabeth's Hospital, Boston 02135

Department of Medicine, Tufts Medical School, Boston 02111

Thorndike Memorial Laboratory and the Harvard Medical Service, Boston 02115

Boston City Hospital, Boston 02118

Department of Medicine, Harvard Medical School, Boston, Massachusetts 02115

Protein Research Laboratory, Bronx Veterans Administration Hospital, Bronx, New York 10468

Department of Medicine, Columbia University College of Physicians and Surgeons, New York 10027

Find articles by Vagenakis, A. in: PubMed | Google Scholar

St. Elizabeth's Hospital, Boston 02135

Department of Medicine, Tufts Medical School, Boston 02111

Thorndike Memorial Laboratory and the Harvard Medical Service, Boston 02115

Boston City Hospital, Boston 02118

Department of Medicine, Harvard Medical School, Boston, Massachusetts 02115

Protein Research Laboratory, Bronx Veterans Administration Hospital, Bronx, New York 10468

Department of Medicine, Columbia University College of Physicians and Surgeons, New York 10027

Find articles by Downs, P. in: PubMed | Google Scholar

St. Elizabeth's Hospital, Boston 02135

Department of Medicine, Tufts Medical School, Boston 02111

Thorndike Memorial Laboratory and the Harvard Medical Service, Boston 02115

Boston City Hospital, Boston 02118

Department of Medicine, Harvard Medical School, Boston, Massachusetts 02115

Protein Research Laboratory, Bronx Veterans Administration Hospital, Bronx, New York 10468

Department of Medicine, Columbia University College of Physicians and Surgeons, New York 10027

Find articles by Foster, A. in: PubMed | Google Scholar

St. Elizabeth's Hospital, Boston 02135

Department of Medicine, Tufts Medical School, Boston 02111

Thorndike Memorial Laboratory and the Harvard Medical Service, Boston 02115

Boston City Hospital, Boston 02118

Department of Medicine, Harvard Medical School, Boston, Massachusetts 02115

Protein Research Laboratory, Bronx Veterans Administration Hospital, Bronx, New York 10468

Department of Medicine, Columbia University College of Physicians and Surgeons, New York 10027

Find articles by Sterling, K. in: PubMed | Google Scholar

St. Elizabeth's Hospital, Boston 02135

Department of Medicine, Tufts Medical School, Boston 02111

Thorndike Memorial Laboratory and the Harvard Medical Service, Boston 02115

Boston City Hospital, Boston 02118

Department of Medicine, Harvard Medical School, Boston, Massachusetts 02115

Protein Research Laboratory, Bronx Veterans Administration Hospital, Bronx, New York 10468

Department of Medicine, Columbia University College of Physicians and Surgeons, New York 10027

Find articles by Ingbar, S. in: PubMed | Google Scholar

Published May 1, 1973 - More info

Published in Volume 52, Issue 5 on May 1, 1973
J Clin Invest. 1973;52(5):1010–1017. https://doi.org/10.1172/JCI107265.
© 1973 The American Society for Clinical Investigation
Published May 1, 1973 - Version history
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Abstract

Studies of the effect of L-thyroxine administration (0.3 mg daily for 7-9 wk) on the peripheral metabolism of 131I-labeled triiodothyronine (T3) and 125I-labeled thyroxine (T4) and on the concentration and binding of T4 and T3 in serum were carried out in 11 euthyroid female subjects. Administration of L-thyroxine led to consistent increases in serum T3 concentration (137 vs. 197 ng/100 ml), T3 distribution space (39.3 vs. 51.7 liters), T3 clearance rate (22.9 vs. 30.6 liters/day) and absolute T3 disposal rate (30 vs. 58 μg/day), but no change in apparent fractional turnover rate (60.3 vs. 60.6%/day). The proportion and absolute concentration of free T3 also increased during L-thyroxine administration. Increases in serum total T4 concentration (7.3 vs. 12.8 μg/100 ml) and in both the proportion and absolute concentration of free thyroxine also occurred. In five of the subjects, the kinetics of peripheral T4 turnover were simultaneously determined and a consistent increase in fractional turnover rate (9.7 vs. 14.2%/day), clearance rate (0.84 vs. 1.37 liters/day), and absolute disposal rate (64.2 vs. 185.0 μg/day) occurred during L-thyroxine administration. Despite these increases in the serum concentration and daily disposal rate of both T4 and T3, the patients were not clinically thyrotoxic. However, basal metabolic rate (BMR) values were marginally elevated and, as in frank thyrotoxicosis, T4-binding capacities of thyroxine-binding globulin (TBG) and thyroxine-binding prealbumin (TBPA) reduced, suggesting that subclinical thyrotoxicosis was present. Thus, the often recommended replacement dose of 0.3 mg L-thyroxine daily may be greater than that required to achieve the euthyroid state.

The studies have also provided additional evidence of the peripheral conversion of T4 to T3 in man and have permitted the calculation that approximately one-third of exogenously administered T4 underwent deiodination to form T3. To the extent that a similar fractional conversion occurs in the normal state, it can be calculated that a major fraction of the T3 in serum derives from the peripheral deiodination of T4 and that only a lesser fraction derives from direct secretion by the thyroid gland.

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