Effects of Phenobarbital on Thyroxine and Triiodothyronine Kinetics in Graves' Disease

Abstract

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.