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

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.