Endocrine Abstracts

Background: Hypercalcaemia can occur in 20–30% of malignancy. Neuroendocrine malignancy-related hypercalcaemia is relatively rare with few reported cases, mostly in pancreatic neuroendocrine tumours. It could be related to humoral hypercalcaemia of malignancy (PTHrP secretion), production of 1,25-dihydroxyvitamin D3 (1,25(OH)₂D3) by the tumour or production of PTH by the tumour^1,2. Here we describe a case of metastatic neuroendocrine tumour with possible extrarenal secretion of 1,25(OH)₂D3, which to our knowledge was previously described in one other case report³.

Clinical case: A 44-year old gentleman had presented with symptoms of tiredness and vague abdominal discomfort for 3 months. Initial tests showed moderate hypercalcaemia with adjusted calcium of 3.28 mmol/l (2.20–2.60 mmol/l). There was mild hypophosphataemia of 0.58 mmol/l (0.80–1.50 mmol/l) suggestive of a PTH-related effect. However, serum PTH was suppressed at 0.2 pmol/l (1.3–9.3 pmol/l). Serum total 25-OH Vitamin D was within reference range at 31.9 nmol/l (25–50 nmol/l) but surprisingly 1,25(OH)₂D3 level was elevated at 142 pmol/l (20–120 pmol/l). PTH-related peptide measurement was not performed due to resource limitations. Urinary calcium:creatinine ratio was 2.00 and urinary calcium excretion was high at 25.3 mmol/24 hours (2.5–7.5 mmol/24 hours) which excluded familial hypocalciuric hypercalcaemia. Serum and urine protein electrophoresis were negative for monoclonal band (paraprotein). CT abdomen demonstrated a large 14 cm retroperitoneal partly enhancing solid and partly cystic/non-enhancing mass in the upper abdomen suspected to be arising from the tail of the pancreas. There was a similar lesion in the right lobe of his liver which was hyperenhancing measuring 8.5 cm, and splenic vein obstruction with numerous collaterals. Ultrasound guided biopsy of his liver lesion showed features of neuroendocrine tumour with strongly positive immunohistochemistry stain for AE1/AE3 and Synaptophysin and weakly positive with Chromogranin and focal positivity with S100. The tumour was negative with PAX-8, Melan-A, SMA, Calretinin, CD31 and Desmin. Ki-67 index was 37.1% indicating a high-grade neuroendocrine tumour.

Hypercalcaemia was acutely managed by intravenous hydration and Zoledronic acid. As the tumour was high-grade with metastases, a decision was made for 3-weekly chemotherapy with Carboplatin and Etoposide, with serial CT monitoring.

Conclusion: Neuroendocrine malignancy should be considered as a potential cause of hypercalcaemia in malignancy. This case illustrates a pancreatic neuroendocrine tumour with possible extrarenal secretion of 1,25(OH)₂D3 level resulting in hypercalcaemia.