ISSN 1470-3947 (print) | ISSN 1479-6848 (online)

Endocrine Abstracts (2019) 66 OC5.4 | DOI: 10.1530/endoabs.66.OC5.4

Tolvaptan for hyponatraemia in infants with brain tumours

Jaya Sujatha Gopal-Kothandapani, Detlef Bockenhauer & Helen Spoudeas


Great Ormond Street Hospital, London, UK


Background: Syndrome of Inappropriate Antidiuretic Hormone secretion (SIADH) is a well-recognized complication of intracranial tumours (ICT). Fluid restriction as treatment for SIADH is challenging in infants since it is coupled with calorie restriction. Moreover, it may conflict with chemotherapy-associated hyperhydration protocols. Existing evidence on the use of the type-2 vasopressin receptor antagonist (Tolvaptan) for refractory SIADH in infants and young children is limited.

Objective: To assess the efficacy and safety of Tolvaptan in managing infants with ICT associated SIADH.

Methods: Retrospective review of clinical data on patients diagnosed with ICT associated SIADH in infancy and treated with Tolvaptan at our quaternary centre (2012 and 2019).

Results: We identified 4 children (2 females; 2 males) matching the entry criteria and data on clinical presentation, management and treatment outcome of SIADH. Three patients (5, 5, 24 months) were diagnosed with suprasellar pilocytic astrocytoma of whom one receiving chemotherapy at the time of SIADH. One diagnosed antenatally with a large supra-and-infra tentorial teratoma was receiving palliative care from 10 days of life. Severe and persistent hyponatremia (range 118–130 mmol/l) occurred in all within 4–8 days of neurosurgical biopsy (2), shunt revision (1) or tumour debulking (1). All patients were euvolaemic, meeting diagnostic criteria for SIADH with normal renal, adrenal and thyroid function. Serum copeptin was elevated in 2 patients. All patients were refractory to initial fluid restriction. Salt supplementation in one patient resulted in hypertension. Tolvaptan was started 4 to 16 weeks after SIADH diagnosis, initially at 0.1 mg/kg per day and titrated up to 1 mg/kg per day according to urine output and plasma sodium (P.Na). P.Na normalised and fluid intake was liberalised without side effects in all patients. In one patient SIADH resolved after 2 weeks of Tolvaptan (maximum dose 0.2 mg/kg per day), the others being switched to Urea [1–1.5 g/kg per day, dose range 2–15 g BD] for cost-effectiveness after > 1 week.

Conclusion: Tolvaptan is a safe and effective therapeutic option in children with intracranial tumours and SIADH to optimise calorie intake and facilitate intravenous hydration during chemotherapy. Close twice daily monitoring of P.Na and urine output to inform safe dose titration during Tolvaptan therapy is imperative.

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