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THYROID HORMONE LEVELS AND PROTEIN BINDING IN PATIENTS ON LONG‐TERM DIPHENYLHYDANTOIN TREATMENT
Author(s) -
HEYMA P.,
LARKINS R. G.,
PERRYKEENE D.,
PETER C. T.,
ROSS D.,
SLOMAN J. G.
Publication year - 1977
Publication title -
clinical endocrinology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.055
H-Index - 147
eISSN - 1365-2265
pISSN - 0300-0664
DOI - 10.1111/j.1365-2265.1977.tb02023.x
Subject(s) - medicine , endocrinology , triiodothyronine , hormone , free thyroxine , thyroid , thyroid hormones , chemistry , thyroid function
SUMMARY The effect of long‐term diphenylhydantoin (DPH) treatment on thyroid hormone concentrations and protein binding was determined in a randomized controlled trial. As has been demonstrated previously, total thyroxine (T4) concentrations were significanly depressed in patients on DPH. There was no significant effect on indirect indices of protein binding of thyroid hormones, and the free thyroxine index (FTI) was also significantly depressed. Triiodothyronine (T3) and thyrotrophin (TSH) concentrations were either unaffected, or only very slightly affected by DPH. Significant effects on the FTI were still apparent 4 weeks after discontinuing treatment. It is concluded that the depression of total T4 levels observed in vivo is not due solely to diminished protein binding, but may instead be largely explained by reports suggesting enhanced degradation of T4 following DPH therapy. Since 1961 it has been known that diphenylhydantoin (DPH) has a significant effect on the levels of the circulating thyroid hormones in the plasma (Oppenheimer et al ., 1961). It is known that the effect is extrathyroidal (Oppenheimer et al ., 1961) and it was initially assumed to be due to an effect on protein binding. This assumption followed the demonstration that DPH decreased the binding of thyroxine (T4) to throxine binding globulin (TBG) in vitro (Oppenheimer & Tavernetti, 1962). However, more recent work (Chin & Schussler, 1968; Larsen et al ., 1970; Hansen et al ., 1974; Stjernholm et al ., 1975) has suggested that there may be a true depression of free T4. Most previous studies have been in epileptic patients for whom the control groups were not totally comparable (Hansen et al ., 1974; Chin & Schussler, 1968) or in normal subjects who underwent DPH therapy for only a short time (i.e. 1‐2 weeks, Hansen et al ., 1974). Moreover, DPH dosage in earlier studies has for the most part been arbitrarily decided upon, or evaluated by clinical signs. It is known that there are extremely variable individual responses to given doses of DPH (Richens & Dunlop, 1975), resulting in variable plasma levels of DPH. This study describes the effects of long‐term DPH treatment on thyroid function and thyroid hormone protein binding. A comparable control group was also studied, and DPH concentration in the blood was continually monitored. The same patients were reexamined after discontinuation of therapy, to elucidate the duration of the effect.