Endocrine Abstracts

Introduction: Hypercalcaemia secondary to malignancy is rare in children. PTH-rP secreted by malignant cells increases bone resorption and renal calcium retention causing hypercalcaemia. We report a case of hypercalcaemia refractory to bisphosphonate and corticosteroid therapy, but responsive to treatment with Denosumab.

Case report: A 17-year-old boy with epidermolysis bullosa presented with advanced squamous cell carcinoma of the left leg and symptomatic hypercalcaemia (serum adjusted calcium, 4.2 mmol/l). PTH was suppressed at 0.7 pmol/l. Serum 25 hydroxy vitamin D level was 31 nmol/l (normal range >50 nmol/l) and serum phosphate 1.51 mmol/l (normal range, 0.74–1.55). The hypercalcaemia was initially managed with hyper hydration and prednisolone, followed by administration of i.v. pamidronate. Following two infusions of pamidronate (1 mg/kg per dose), serum calcium fell to 2.87 mmol/l with improvement in symptoms. However the hypercalcaemia relapsed within a week (serum calcium, 3.61 mmol/l) and despite aggressive management with intravenous fluids, prednisolone, oral phosphate and two further doses of pamidronate, there was only temporary normocalcaemia (serum calcium 2.58). 72 h later the patient was once again symptomatic with serum calcium 3.39 mmol/l. As the hypercalcaemia was refractory to bisphosphonate treatment, he was given a trial dose of SUBCUTANEOUS Denosumab (60 mg), following which the calcium fell to 2.86 mmol/l within 24 h and normocalcemia was sustained a week later. No adverse effects were noted.

Conclusion: We report a case of refractory hypercalcaemia secondary to malignant squamous cell carcinoma, which responded well to Denosumab therapy. To our knowledge, this is the first case of humoral hypercalcaemia of malignancy managed with Denosumab in the paediatric population. Denosumab could be considered as a treatment option in patients with bisphosphonate resistant hypercalcaemia.