Cyclophosphamide-Induced Hyponatremia in a Patient With Diabetes Insipidus

Abstract

Cyclophosphamide has been previously observed to induce hyponatremia. The mechanism remains unclear. Cyclophosphamide may produce a syndrome of inappropriate anti-diuretic hormone-like phenomenon through impairment of the kidneys ability to dilute urine. Whether cyclophosphamide or its metabolites have a direct effect on the kidney, a vasopressin-like effect on the kidney, or cause vasopressin release is unknown. A 29-year-old man with intracranial germinoma diagnosed at age 11 treated primarily with chemo-radiation developed a recurrence 17 years later and was noted to have panhypopituitarism with resultant central diabetes insipidus. He was admitted for chemotherapy with cisplatin, cyclophosphamide and mesna. His admission serum sodium was normal, but he became hyponatremic while undergoing chemotherapy with cyclophosphamide and mesna in conjunction with the initiation of intravenous hydration with 5% dextrose/0.45% normal saline despite withholding two doses of desmopressin (DDAVP). The sodium eventually normalized after administration of 20 mg intravenous furosemide. A similar episode occurred several weeks later, while again receiving cisplatin, cyclophosphamide and mesna chemotherapy. He again became hyponatremic despite receiving isotonic saline fluids and withholding DDAVP during cyclophosphamide treatment. Serum sodium did not improve with three doses of 10 mg intravenous furosemide but improved instead with sodium chloride tablets. The mechanism of cyclophosphamide-induced hyponatremia remains unknown. Given that this patients central diabetes insipidus prevents him from secreting increased amounts of anti-diuretic hormone, hyponatremia is likely induced by a direct nephrogenic effect of cyclophosphamide or its metabolites.




J Endocrinol Metab. 2015;5(6):337-339
doi: http://dx.doi.org/10.14740/jem319w