INHIBITORY EFFECT OF DIPHENYLHYDANTOIN ON THE FEEDBACK CONTROL OF CORTICOTROPHIN RELEASE

Abstract

ABSTRACT Suppression of plasma corticosteroids by dexamethasone was studied in 4 control subjects before and during treatment with diphenylhydantoin (DPH), and also in 14 epileptic patients, 13 of whom received DPH while one received primidone. At 8 a. m. the mean value of plasma corticosteroids in 31 normal subjects 9 hours after one mg of dexamethasone given orally was less than 4.4 μg/100 ml, but in the epileptic patients the plasma corticosteroids were not suppressed to this control level. Similar experiments in the control subjects demonstrated that during treatment with DPH an insufficient response to one mg dexamethasone is found. When suppression with 2 mg of dexamethasone given orally was repeated in 4 epileptic patients and in two control subjects receiving DPH, the plasma corticosteroids still did not decrease below 4.4 μg/100 ml. After 4 mg of dexamethasone, however, the plasma corticosteroids were suppressed to values of about 4.4 μg/100 ml in 4 out of 7 epileptic patients and in two control subjects receiving DPH. A normal diurnal rhythm of plasma corticosteroids was found in 7 out of 9 epileptic patients and in 3 control subjects receiving DPH. Krieger (1962) and Rinne (1966) observed a limited response to metyrapone in patients treated with DPH. This observation and the insufficient suppression of plasma corticosteroids by dexamethasone found in patients receiving DPH, is most likely a consequence of a partial inhibition of the feedback control of corticotrophin (ACTH) release. Since DPH does not appear to interfere with diurnal rhythm of ACTH release, it is most unlikely that the diurnal rhythm of ACTH release is dependent solely on a negative feedback mechanism. In patients receiving DPH, the metyrapone test and the one mg dexamethasone test are of no value in the diagnosis of pituitary-adrenal diseases.