We studied the effect of diphenylhydantoin (DPH) on TRH-stimulated TSH secretion in four patients (three of whom had hypothyroidism; one treated with L-T4), in euthyroid rats, and in dispersed rat anterior pituitary cells in short term tissue culture. DPH treatment of four patients (100 mg, three times daily for 14 days) caused a 22% decrease in mean serum T4 (P < 0.06), a 31% decrease in mean serum free T4 (P < 0.01), and a 6% decrease in mean serum T3. Mean basal serum TSH was unchanged, but the integrated TSH response after TRH injection (500 μg, iv) decreased 28% (P < 0.06) and 51% (P < 0.01) after 7 and 14 days of DPH treatment, respectively. Changes in the integrated PRL response to TRH did not correlate with those in TSH. Injection of DPH into euthyroid rats (5 mg/100 g BW·day for 9 days) caused a significant decrease in mean serum T4 but no change in TSH release after TRH treatment. However, 1 h after a large dose of DPH (20 mg/100 g BW), there was a marked reduction (58%) in TRH-induced TSH release. DPH injections into athyreotic rats (5 mg/100 g BW every 8 h for 48 h) caused a significant increase in pituitary TSH (P < 0.01) but no significant decrease in plasma TSH. DPH inhibited TSH release from cultured anterior pituitary cells. In the presence of 10-7 M TRH, DPH (10-4 M) caused a 74% decrease in TSH release (P < 0.001); the inhibition produced by T3 (10-7 M) was only 14% (P < 0.05). These studies suggest that DPH inhibits TRH-induced TSH release in man, euthyroid rats, and cultured rat anterior pituitary cells. Thus, in DPH-treated patients with decreased serum T4 and free T4, the observed normal serum TSH when one would expect elevated serum TSH may result from drug-induced inhibition of TRH action on TSH release.
ASJC Scopus subject areas
- Endocrinology, Diabetes and Metabolism
- Clinical Biochemistry
- Biochemistry, medical