Inhibition of Antidiuretic Hormone Secretion by Diphenylhydantoin

INCREASED secretion of antidiuretic hormone (ADH) has been implicated in many hyponatremic disorders associated with impaired water excretion. This increased ADH release may be due to nonosmotic stimulation in response to volume depletion, to certain pharmacological agents, or frequently to an "inappropriate" ADH secretion secondary to tumors, pulmonary disease, or central nervous system (CNS) disease.¹The only previously known chemical inhibitor of ADH release other than water is ethanol.²More recently, Lee et al³have shown that diphenylhydantoin corrected the impaired water excretion of two patients with the syndrome of inappropriate ADH secretion. To further clarify the mechanism of ADH inhibition by diphenylhydantoin sodium (Dilantin) we have studied the effect of this drug in six patients with the inappropriate ADH syndrome and in eight normal subjects. Materials and Methods All clinical studies were performed in the Clinical Research Center of the University of Southern California School