Vincristine Neurotoxicity and Abnormal Secretion of Antidiuretic Hormone

The secretion of the antidiuretic hormone, arginine vasopressin, has been studied in a patient who developed peripheral neuropathy and the syndrome of inappropriate antidiuresis during therapy with vincristine sulfate. The patient's plasma arginine vasopressin concentration, determined by a radioimmunoassay technique, was markedly increased despite profound hyponatremia and rose even higher following correction of the electrolyte imbalance. In six other vincristine-treated patients, in whom neither neuropathy nor inappropriate antidiuresis was observed, plasma arginine vasopressin concentration was in the normal range. These findings indicate that the inappropriate antidiuresis, which can occur during vincristine therapy, is associated with an abnormal increase in arginine vasopressin secretion. This complication appears to be related to the other neurotoxic effects of the drug and may be due to an alteration in the normal osmoreceptor control of vasopressin secretion.