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Simultaneous measurements of the peripheral kinetics of thyroxine (T4) and triiodothyronine (T3) were made in hyperthyroid patients before and during the administration of phenobarbital (PB). The following alterations in T4 kinetics were noted during PB: Total clearance increased on the average by 18% (p < 0.05). Fecal T4 clearance, calculated from total clearance and the urinary fraction, increased by 103% (p < 0.01). Serum levels of total and free T4 tended to decline during PB, but the changes were variable in magnitude and not proportional to the increments in total clearance. Total T4 pool size and absolute disposal rate were not significantly altered during PB in the group as a whole. As controls, two hypothyroid patients who were being maintained on constant daily doses of T4 were studied. In both, total and fecal T4 clearance increased and serum T4 declined during PB administration. Hepatic T4 distribution volume rose during PB in 2 of the 3 subjects in whom this measurement was made. In 6 of the hyperthyroid patients small decreases occurred during PB in serum T3 concentration, total and fecal clearance, but the changes were not significant. Absolute T3 disposal rate declined by 25% in this group. The findings in regard to T4 metabolism are consistent with the known effect of PB on T4 kinetics in the rat, i.e., an augmentation of T4 clearance primarily via the fecal route secondary to stimulation of hepatic cellular mechanisms of hormone removal. In individuals with a relatively fixed rate of T4 supply, due either to untreated hyperthyroidism or to the administration of a constant replacement dose of T4) the PB-enhanced removal of hormone results in a decline in the level of circulating T4.
Cavalieri et al. (Wed,) studied this question.