Refractory Hypercalcemia Caused By PTHrP Secretion from Metastatic Pancreatic Neuroendocrine Tumor
Presentation Number: SAT 329
Date of Presentation: April 1st, 2017
Ji Wei Yang*1, Zu-hua Gao2 and Richard Kremer1
1McGill University Health Center, Montreal, QC, Canada, 2McGill University Health Centre, Montreal, QC, Canada
Background: PTHrP secretion by gastroenteropancreatic neuroendocrine tumors (NET) is extremely rare. The treatment of hypercalcemia in this context can be challenging. Clinical case: A 53-year-old man was referred for the evaluation of a pancreatic NET with concomitant severe hypercalcemia. The patient’s past medical history was significant for type 2 diabetes. His family history was positive for breast and ovarian cancers in his mother and 2 sisters. The patient was started on lanreotide 120 mcg SC every 4 weeks shortly after the diagnosis of pancreatic NET. He initially presented to the hospital with abdominal pain, night sweats and a 20-lbs weight loss over 3 months. He was found to have severe hypercalcemia refractory to multiple treatment modalities, including aggressive hydration, zoledronic acid 4 mg IV, pamidronate 180 mg IV and denosumab 60 mg SC every 4 weeks. Early laboratory investigations showed total calcium 3.51 mmol/L (2.12-2.62 mmol/L), ionized calcium 1.89 mmol/L (1.15-1.32 mmol/L), albumin 42 g/L (38-52 g/L), magnesium 0.49 mmol/L (0.75-1.05 mmol/L), phosphate 0.54 mmol/L (0.80-1.45 mmol/L), PTH < 0.80 mmol/L (1.50-9.30 pmol/L), 25-(OH)D 50 nmol/L (50-125 nmol/L), 1,25-(OH)2D3 158 pmol/L (90-174 pmol/L), and 24-hour urinary calcium 1.0 mmol/day (2.5-7.5 mmol/day). Imaging done before treatment with lanreotide showed a 12.4 cm lesion occupying the body and tail of the pancreas, with metastases to the liver. Biopsy of the liver metastases confirmed neuroendocrine carcinoma. The specimen stained positive for CK19, synaptophysin and chromogranin, and exhibited cytoplasmic and membranous positivity for PTHrP. PTHrP staining was done using a monoclocal antibody directed against the PTHrP N-terminal (PTHrP 1-34). Interestingly, circulating levels of PTHrP measured by an immunoradiometric assay (PTHrP IRMA, Beckman Coulter) yielded normal levels despite on-going hypercalcemia. Nephrogenous cycle AMP, a surrogate marker of PTHrP activity, was elevated at 5.0 nmol/dL (1.3-3.7 nmol/dL). This indicates that the circulating PTHrP moieties in our patient were likely not recognized by the 2-site assay specific for PTHrP 1-86. We therefore hypothesize that the NET secreted a shorter form of PTHrP with an intact N-terminus. The patient underwent extensive debulking surgery. Post-op course was complicated by severe hypocalcemia likely induced by the removal of the PTHrP-secreting NET (similar to hungry bone syndrome following parathyroid surgery) with total calcium reaching a nadir of 1.36 mmol/L (2.12-2.62 mmol/L), requiring oral calcium and calcitriol supplementation. Conclusion: We report a case of refractory PTHrP-mediated hypercalcemia in the context of metastatic pancreatic NET. The normal PTHrP levels add to the interest of this case as we hypothesize that the NET likely secreted a shorter form of PTHrP not recognized by a commonly used commercial assay.
Nothing to Disclose: JWY, ZHG, RK