Endocrine Abstracts

Case Summary: We report a case of a 79 yr old female with multiple co-morbidities including diabetes mellitus, hypertension, recurrent TIAs, CABG (2015), HfpEF and osteoporosis. Following treatment for the latter with Denosumab 60 mg, the patient developed hypocalcaemia (1.87 -2.13 mmol/l) with appropriately raised PTH (7.2 - 457.4 pmol/l). Her 25 hydroxy vitamin D level was 99 nmol/l. Her hypocalcaemia was managed with alfacalcidol and intravenous and then oral calcium supplements. Over a period of 4 months, these were withdrawn, and the patient maintained a normal calcium off supplements for 1 month. The patient then developed sepsis requiring prolonged admission to ITU for 33 days. During this period of her inpatient stay, she developed hypercalcemia (2.60-3.24 mmol/l) with a suppressed PTH. Her serum ACE and electrophoresis were normal. Her PET-CT scan demonstrated no evidence of malignancy. Her hypercalcaemia was suspected to be secondary to immobility and possibly rebound hypercalcemia after the discontinuation of denosumab. Treatment was with rehydration and bisphosphonates following which her calcium normalized. Immobilization is a recognized cause of hypercalcaemia. This is associated with a suppressed PTH, as in our case. Its onset is usually in 4 to 6 weeks after the precipitating injury/immobilization and calcium levels are usually no higher than 2.99 mmol/l?????. Severe hypercalcemia with levels > 4.31 mmol/l, have been rarely described in the literature. Risk factors included prolonged inpatient stay (e.g. 6 months), sepsis (inflammatory cytokines accelerate osteoclastic resorption), chronic kidney disease stage 4, ITU stay, young age, spinal cord injury????. Rebound hypercacalcemia after discontinuing Denosumab has also been described in the literature. So far 6 cases have been reported amongst which 4 have been reported in pediatric population. Such cases are also associated with suppressed PTH levels, as in our case. Its onset is usually in 7 weeks to 6 months after discontinuing this drug and the severity of hypercalcaemia ranges between 2.5 to 3.79 mmol/l in adults. The mechanism may involve rebound osteoclast activity. Gradual tapering of denosumab dosage or prophylactic administration of bisphosphonates may prevent such cases. The management options for hypercaclaemia due to these two causes include hydration, bisphosphonates, corticosteroids, calcitonin, etc. Others have suggested that in severe cases, repeated use of bisphosphonates or reinjection of denosumab may be required to repress the surge of calcium released into the circulation.