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

Area of Science:

• Pediatric Oncology
• Endocrinology
• Molecular Targeted Therapy

Background:

• Adamantinomatous craniopharyngiomas (ACPs) are rare sellar-suprasellar tumors causing significant morbidity, often impacting the pituitary gland and leading to central diabetes insipidus (CDI).
• Trametinib, a MEK1/MEK2 inhibitor targeting the MAPK pathway, is used in various cancers, but its use in ACPs is limited, with potential toxicities like hyponatremia.
• Patients with pre-existing CDI may have fragile fluid balance, requiring careful management, especially when initiating new systemic therapies.

Purpose of the Study:

• To report a case of severe hyponatremia in a pediatric patient with progressive ACP and brittle CDI during trametinib therapy.
• To highlight the potential interaction between trametinib and desmopressin management in patients with CDI.
• To emphasize the need for vigilant monitoring of serum sodium and desmopressin requirements in this specific patient population.

Main Methods:

• Detailed clinical case report of a pediatric patient with multiply progressive ACP and established CDI.
• Administration of trametinib for ACP treatment.
• Close monitoring of serum sodium levels and desmopressin dosage adjustments throughout trametinib therapy and upon its cessation.

Main Results:

• The patient developed severe hyponatremia shortly after initiating trametinib, necessitating a significant reduction in desmopressin dosage.
• Upon cessation of trametinib, the patient experienced a rapid rebound in desmopressin requirement, indicating a direct effect of the drug on fluid balance regulation.
• Serum sodium levels fluctuated significantly, correlating with trametinib treatment status and desmopressin titration.

Conclusions:

• Trametinib therapy can precipitate severe hyponatremia in pediatric patients with ACP and central diabetes insipidus.
• Close monitoring of serum sodium and proactive adjustment of desmopressin doses are crucial when initiating or discontinuing MEK inhibitors in patients with CDI.
• This case underscores the importance of understanding drug-specific toxicities and their management in complex pediatric endocrine-oncology scenarios.