Endocrine Abstracts

Background: Hypercalcaemia of malignancy (HCM) is the commonest metabolic complication of malignancies. However, this is relatively rare among patients with neuroendocrine tumors (NET). Management of HCM remains a challenge for clinicians, especially in cases of refractory hypercalcaemia.

Case Report: A 37-year-old lady was referred to the NET service in June 2021 following the finding on imaging of a huge inoperable pancreatic mass with peritumoural varices and liver metastases. Biopsy revealed a well differentiated Grade 2 pancreatic NET (pNET) and somatostatin analogue therapy was commenced. On tumour progression, she completed 4 cycles of peptide receptor radionuclide therapy (PRRT) in May 2022. Her condition was complicated by development of Type 3c Diabetes Mellitus, episodes of variceal bleed and symptomatic hypercalcaemia [corrected calcium 3.09mmol/l (N 2.14-2.56); phosphate 0.43mmol/l (N 0.8-1.5); parathyroid hormone 0.5 pmol/l (N 1.6-6.9)], where confusion and lethargy were predominant features. She responded well to saline diuresis and intravenous Zolendronic Acid (ZA), maintaining a stable calcium level for a year. Her condition deteriorated thereafter when she was hospitalised for severe hypercalcaemia on two occasions (corrected calcium of 3.34mmol/l and 3.7mmol/l respectively) despite receiving monthly ZA and was switched over to monthly subcutaneous Denosumab 120 mg. Despite this, calcium level drifted above 3.0mmol/l before the next dose and the dose interval was shortened to two-weekly and then weekly. Over the last two months, weekly Denosumab 120 mg and daily home fluid administration have minimised her hospital admissions for symptomatic hypercalcaemia. Due to bleeding risk and performance status, other active treatments were not possible, but control of the hypercalcaemia has allowed quality time with her family.

Conclusion: HCM in pNET is associated with a poor prognosis and is highly refractory to treatment. To our knowledge, this is the longest period of weekly high dose Denosumab usage and illustrates an alternative approach in such difficult cases.