Endocrine Abstracts

Introduction: We present the case of a 14-year-old boy with refractory hypercalcaemia secondary to Denosumab cessation. This case is unique due to his extensive treatment course and relapse during therapy.

Background: Denosumab is a monoclonal antibody used in the treatment of osteoporosis, skeletal metastasis, and giant cell tumour of bone. In skeletally immature patients, studies have proven its effectiveness in suppressing bone resorption and alleviating symptoms, however refractory hypercalcemia often follows the discontinuation of Denosumab treatment.

Case: Our patient, who also has Noonan syndrome, was commenced on Denosumab for bilateral giant cell granuloma of the jaw. He completed two years of 120 mg monthly subcutaneous injections, followed by a four month wean. Prophylactic Zoledronic acid was given during weaning. Unfortunately, despite this, he developed hypercalcaemia four months post cessation of Denosumab. He was initially managed with hyperhydration at 3L/m²/day and Pamidronate. He developed an acute kidney injury (AKI) three weeks into treatment and Pamidronate was no longer effective. Calcitonin was commenced at 4units/kg subcutaneously with a good response. Further doses given intramuscularly were briefly effective but very painful, so treatment was switched to intravenous administration. Creatinine peaked at 144umol/l (AKI stage 3, baseline 40umol/l) and Corrected Ca (cCa) peaked at 4.02 mmol/l. He required Calcitonin every 24-48 hours and due to tachyphylaxis he required weekly 1unit/kg dose increases. Hyperhydration was weaned to maintenance intravenous fluids to achieve a neutral fluid balance and renal function slowly improved.

Progress: Throughout his admission he remained symptomatic of hypercalcaemia at cCa >3.0 mmol/l, a level he reached almost daily. Nausea was the predominant symptom and unfortunately after four weeks he had lost 12% of his admission weight and required nasogastric feeding for supplementation. Eight weeks into treatment he contracted Norovirus and shortly after, rebound hypercalcaemia appeared to resolve; facilitating discharge. Unfortunately, within two weeks, he became symptomatic of hypercalcaemia again requiring readmission for treatment. In total, he completed ten weeks of progressively increasing Calcitonin dosing to a maximum 10units/kg with a final dose of Pamidronate at 1 mg/kg before cCa remained consistently <3.0 mmol/l. Six months following onset of his hypercalcaemia his cCa is finally within range at 2.59 mmol/l.