Endocrine Abstracts

Hyponatremia is the most common electrolyte disorder in hospitalized patients, including cancer patients. Multiple causes can lead to hyponatremia, but frequently this electrolyte disorder is due to the syndrome of inappropriate antidiuresis (SIAD). In cancer patients this syndrome is mostly secondary to ectopic secretion of arginine vasopressin by tumoral cells. In addition, several chemotherapeutic drugs induce the release of arginine vasopressin by the hypothalamus. There is evidence that hyponatremia is associated to a more negative outcome in a number of pathologies, including cancer. Many studies have demonstrated that in different cancer types both the progressionfree survival and the overall survival are negatively affected by hyponatremia, whereas the correction of serum [Na+ ] has a positive effect on patients’ outcome. Tolvaptan, a vasopressin receptor type 2 antagonist, has been approved more than a decade ago in Europe for the treatment of hyponatremia secondary to SIAD. Tolvaptan effectively corrects hyponatremia and the risk of overcorrection can be minimized by frequent monitoring of serum [Na+ ] in the 24 hours after initiation of therapy and by avoiding concurrent use of other hyponatremia treatments. Interestingly, tolvaptan has been also approved for the treatment of autosominal dominant polycystic kidney disease. In this disease tolvaptan, at higher doses than dose used for the treatment of SIAD, counteracts cystogenesis by inhibiting the cAMP/PKA pathway. This unpredicted antiproliferative effect of tolvaptan led us to hypothesize that this molecule might counteract tumor cells growth. In vitro evidence confirmed this hypothesis and in different cancer cell lines (i.e. neuroblastoma, hepatocarcinoma, small cell lung cancer, colon cancer) tolvaptan effectively reduced cell proliferation and invasiveness. These results might thus open a new scenario, in which vasopressin type 2 receptor antagonists might have a role among pharmacological strategies against cancer, in addition to their effect in correcting hyponatremia. - Hyponatremia is the most frequent electrolyte alteration in hospitalized patients; - The most frequent cause of hyponatremia in cancer patients is the Syndrome of Inappropriate Antidiuresis (SIAD); - Hyponatremia is associated with a worse outcome in cancer patients; - The vasopressin receptor type 2 antagonist tolvaptan effectively corrects hyponatremia in SIAD; - In vitro evidence indicated that tolvaptan has an unpredicted antiproliferative effects in cancer cell lines, thus possibly opening a new scenario in treatment strategies against cancer.