Thyroid-function tests in diphenylhydantoin-treated patients

We compared the free-thyroxine index in normal adults and in euthyroid patients taking diphenylhydantoin. All subjects had normal serum thyrotropin concentrations. Serum thyroxine concentrations were determined by two commonly used competitive protein-binding assays, which yielded slightly different values, but which consistently showed the same degree of decrease in mean serum thyoxine concentration in drug-treated patients as compared to the normal subjects. When 14C-labeled diphenylhydantoin was added to serum before the assay, it was separated from thyroxine in the Ames method, whereas by the Murphy-Pattee method both drug and thyroxine were extracted together. Thus, the decrease in serum thyroxine concentrations during diphenylhydantoin therapy cannot be the result of drug interference with the binding of thyroxine to binding proteins in the assays. Triiodothyronine uptake, evaluated by two methods, was identical in the two groups. The free-thyroxine indexes for all normal persons were within the manufacturer's normal range, but 21% of the drug-treated patients had subnormal indexes by the Ames method; the indexes as measured by the Murphy Pattee method were in the lower half of the normal range. Because the triiodothyronine uptake was unaffected by the drug treatment, the decreases in the indexes must have resulted from the lower serum thyroxine concentrations. We conclude that the free-thyroxine index may not provide a valid estimate of either the clinical status or the free-thyroxine concentration in patients taking diphenylhydantoin.