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

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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.

Authors

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