Endocrine Abstracts

Case history: A 51 year old gentleman presented to ED with severe right thigh pain, a 6 month history of weight loss, and 2 weeks of polyuria. He had no medical history and took no regular medications. He worked as a postman, was a non-smoker and non-drinker.

Investigations: Bloods showed adjusted calcium of 5.04 mmol/l, parathyroid hormone (PTH) 1.4 pmol/l, and alkaline phosphatase 438 IU/l. Vitamin D was reported one week later as 37 nmol/l. His haemoglobin was 155 g/l and platelets were 46×10⁹/l. His creatinine was 214 umol/l (nil previous). His prostate specific antigen was 2333 ug/l. A CT showed diffuse axial lytic skeletal changes and a bone marrow was consistent with metastatic carcinoma.

Results and treatment: Following 48 h of intravenous hydration and calcitonin, he had large volume haematemesis secondary to severe oesophageal ulceration. His calcium remained elevated at 4.74 mmol/l. He was transferred to ITU where he received 7 days of haemofiltration and 2 doses of denosumab 60 mg. He was commenced on bicalutamide and goserelin for presumed prostate carcinoma. 3 days after stopping filtration and 8 days after his last dose of denosumab his calcium dropped to 1.49 mmol/l. His calcium was supplemented parentally and he was discharged with alfacalcidol 1 mcg, colecalciferol 1000 units OD and sandocal 2 tablets QDS. Despite good compliance, our patient was readmitted a week later with an adjusted calcium of 1.29 mmol/l, PTH of 42 pmol/l, and vitamin D of 41 nmol/l. He was treated again with parental calcium supplementation, IV magnesium, and given intramuscular ergocalciferol 50 000 units. He was discharged on 2.5 mcg alfacalcidol OD. Twice weekly bloods showed a normal calcium. 3 weeks later, he was readmitted with symptomatic hypercalcaemia (4.81 mmol/l, and an acute kidney injury (AKI). He required further haemofiltration, and a further dose of denosumab 60 mg, but subsequently became hypocalcaemic. He remains on alfacalcidol 0.25 mg, sandocal and colecalciferol 1000 units OD and most recent blood tests show a calcium of 2.30 mmol/l. His most recent PSA had dropped to 174 ug/l.

Conclusion: We present a case of severe hypercalcaemia, with a number of management challenges. A bisphosphonate was contraindicated due to oesophageal ulceration and severe AKI, and therefore denosumab, a RANK Ligand inhibitor was used. With a long elimination half-life, denosumab can produce severe, prolonged hypocalcemia requiring hospitalisation for aggressive IV calcium and vitamin D supplementation. Preventing this complication via careful baseline assessment, calcium and vitamin D coadministration, and monitoring, is crucial for patients.