Endocrine Abstracts

Rapid correction of chronic hyponatremia can cause osmotic demyelination syndrome(ODS). Recent days, vasopressin receptor antagonists(VAs) are clinically used for the treatment of congestive heart failure or hyponatremia including SIADH. To date, few cases of ODS caused by VAs have reported; however, it is presumed that the treatment with VAs for severe hyponatremia may be associated with an increased risk of ODS. Therefore, in this study, we investigated whether rapid correction of hyponatremia with tolvaptan has a risk of inducing ODS in SIADH model rats. Hyponatremia was induced by liquid diet feeding and subcutaneous desmopressin infusion using osmotic pumps. Seven days later, hyponatremia(approximately 105 mEq/l) was corrected by the following ways; i) bolus administration of hypertonic saline (HS group), ii) oral administration of tolvaptan 1 mg/kg (T1 group), iii)5 mg/kg (T5 group), iv)10 mg/kg (T10 group), or v)removal of osmotic pumps (PO group). The serum sodium levels were increased approximately by 30 mEq/l in 24 h in all groups and there was no significant difference in the degree of sodium elevation. Accordingly, most rats in all groups showed serious neurological impairment. Five days after the correction, the incidence of neurological findings including gait abnormality, paralysis, seizure, or death was respectively 75%, 50%, 66%, 66%, and 88% in HS, T1, T5, T10, and PO group, respectively. Immunohistochemical analysis confirmed the demyelination and the accumulation of microglia in the cerebral cortex and the neighborhood of the red nucleus in the midbrain in all groups. These results suggest that overly rapid correction of severe hyponatremia with a relatively high dose of VAs associated with the blockage of vasopressin action as well as hypertonic saline poses a risk of inducing ODS and that clinicians using VAs to treat hyponatremia need to monitor serum sodium carefully to avoid overcorrection.

Declaration of interest: The authors declare that there is no conflict of interest that could be perceived as prejudicing the impartiality of the research project.

Funding: This research did not receive any specific grant from any funding agency in the public, commercial or not-for-profit sector.