Lowering effect of diphenylhydantoin on serum free thyroxine and thyroxine binding globulin (TBG)

To evaluate the effect of anticonvulsants on serum levels of free thyroxine (FT4) and thyroxine-binding globulin (TBG), 32 patients with epilepsy receiving long-term anticonvulsant treatment (mean duration 81.8 +/- 8.9 months) were employed in the present study. The serum levels of total thyroxine (TT4), total triiodothyronine (TT3), T3 resin uptake (T3U) and thyrotrophin (TSH) were also measured. Free thyroxine index (FT4I) was calculated from TT4 and T3U. Mean levels of these thyroid function tests were as follows: 5.52 +/- 1.51 micrograms/dl (TT4), 1.16 +/- 0.32 ng/dl (FT4), 101.5 +/- 16.2 ng/dl (TT3), 27.5 +/- 2.6% (T3U), 19.64 +/- 3.97 micrograms/ml (TBG), 1.50 +/- 0.36 (FT4I) and 2.21 +/- 0.18 microU/ml (TSH). These values except for T3U and TSH were significantly lower than normal values (P less than 0.01). Using correlation analysis, a significant dose-dependency (daily doses) was found between diphenylhydantoin (DPH) and TT4, FT4 and TBG. Other anticonvulsants (barbiturates, carbamazepine, primidone) or duration of treatment were not significantly correlated with thyroid function tests. Therefore serum levels of DPH were also measured in 19 out of 32 patients receiving anticonvulsant treatment. Significant negative correlation was found between serum levels of DPH and FT4 (r = -0.65) and DPH and TBG (r = -0.61).