Endocrine Abstracts

Introduction: Hypercalcaemia is well associated with metastatic malignancy. Hypocalcaemia is an uncommon complication of osteoblastic metastases and occurs most commonly with breast and prostate carcinoma.

Case: A 46-year-old woman with metastatic breast carcinoma and osteoblastic skeletal metastases treated with denosumab presented with severe symptomatic hypocalcaemia. Serum calcium was persistently low with a nadir value of 1.45 mmol/l (2.2–2.6) and predated the use of denosumab. 25OH-cholecalciferol level was low (24.1 nmol/l). Serum PTH was inappropriately normal at 4.3 (1.3–7.3) for the prevailing level of hypocalcaemia suggesting hypoparathyroidism. Renal function and magnesium were normal.

Management: Treatment with intravenous calcium gluconate was instituted during symptomatic episodes. Vitamin D deficiency was managed with high dose choleclaciferol (20 000 IU, three times a week for 12 weeks) and oral calcium equivalent to 6 g of elemental calcium was commenced. Symptomatic hypocalcaemia persisted despite progressively increasing doses of elemental calcium (final dose 9 g). In view of persistent hypocalcaemia, treatment with Bendroflumethiazide 2.5 mg/day and Alfacalcidol 1 μg/day was instituted. The dose of Alfacalcidol was incrementally increased to 8 μg/day. Normocalcaemia was achieved in 16 weeks.

Discussion: Hypocalcaemia is an uncommon complication of malignancy and is caused by osteoblastic bone metastases. The putative mechanism is increased uptake of calcium by osteoblastic lesions. Hypocalcaemia in our patient was exacerbated by denosumab therapy and vitamin D deficiency. However, hypoparathyroidism in the context of severe hypocalcaemia was suggestive of impaired parathyroid reserve presumed secondary to microscopic malignant infiltration of the parathyroid glands.

Conclusion: Malignancy-related hypocalcaemia occurs almost exclusively with osteoblastic bone metastases and is generally associated with secondary hyperparathyroidism. Our case highlights the fact that microscopic malignant infiltration of the parathyroid glands can occur with advanced malignancy and result in severe refractory hypocalcaemia. Supraphysiological doses of elemental calcium and vitamin D are generally required to induce and maintain normocalcaemia.