Trametinib-induced Hyponatremia in a Patient With Craniopharyngioma and Diabetes Insipidus

Adamantinomatous craniopharyngiomas (ACPs) are rare, sellar-suprasellar benign tumors that cause considerable morbidity and mortality due to local invasion and treatment-related damage to surrounding structures, including central diabetes insipidus (CDI). Trametinib is a highly selective inhibitor of MEK1 and MEK2, which has been evaluated in both adult and pediatric cancers/ tumors with activation of the oncogenic mitogen-activated protein kinase (MAPK) pathway. Despite being thought to have fewer side effects than conventional cytotoxic chemotherapy, off-target toxicities such as hyponatremia have been described. The use of MEK inhibitors in ACPs are limited to case reports and a phase II trial is currently underway. We report a pediatric patient with multiply progressive ACP and known brittle CDI who developed severe hyponatremia associated with a significant decrease in desmopressin dosing after starting trametinib and a rapid rebound of desmopressin requirement with its cessation. We recommend close monitoring of serum sodium levels and a review of desmopressin doses in patients with CDI when started on treatment with MEK inhibitors.