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

Endocrine Abstracts (2016) 45 P8 | DOI: 10.1530/endoabs.45.P8

Denosumab therapy for hypercalcaemia of malignancy in a young child

Abiramy Saravanamuthu1, Harshini Katugampola1, Grace Collard2, Cristina Matei2 & Catherine Peters1

1Great Ormond Street Hospital NHS Trust, London, UK; 2Lister Hospital NHS Trust, Hertfordshire, UK.

Introduction: Hypercalcaemia secondary to malignancy is rare in childhood. Bisphosphonates have previously been shown to be effective in managing such cases in adults, however caution must be exercised in patients with renal failure or respiratory compromise. Denosumab, a RANKL monoclonal antibody is a very potent inhibitor of osteoclasts and can induce hypocalcaemia. It is not excreted by the kidney. Limited trials in adults have shown denosumab to have greater efficacy compared to bisphosphonates in treating hypercalcaemia of malignancy.

Case: A three-year-old girl presented with a brief history of fever, anorexia and vomiting. She was severely hypercalcaemic (cCa 4.88 mmol/l), with an undetectable PTH. She also had evidence of acute kidney injury. Despite hyperhydration and furosemide, the cCa rose to 5.63 mmol/l, and remained elevated following the initiation of calcitonin treatment. Her blood film was suspicious of blasts. A bone marrow aspirate (BMA) was considered crucial at this point to make a diagnosis. Given the situational urgency, and previous reports of hypercalcaemia of malignancy refractory to bisphosphonate therapy, a trial dose of denosumab was administered. The cCa fell to 4.33 mmol/l, enabling a BMA to be carried out. This confirmed a diagnosis of acute lymphoblastic leukaemia and definitive treatment was started. Normocalcaemia was achieved within 48 hours and sustained.

Conclusions: This highlights a rare case of profound hypercalcaemia as a presentation of malignancy in a young child, which responded well to denosumab therapy, enabling an urgent diagnosis to be made and appropriate management to be instigated in a timely manner. Treatment with denosumab may be considered for refractory hypercalcaemia in children, particularly if renal failure is a complication.

Novel Insights: This case highlights the youngest child to our knowledge to be treated with denosumab for hypercalcaemia of malignancy. The use of denosumab in the context of severe hypercalcaemia with renal failure, enabled an urgent definitive diagnosis to be made and appropriate treatment of the underlying cause to be initiated in a timely manner. This suggests denosumab may be a viable first line treatment option in cases such as this and its use in children should be considered for further evaluation in clinical trials.

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