Case Report: Metastatic Duodenal Neuroendocrine Tumor: A Rare Cause of Humoral Hypercalcemia of Malignancy

<ns3:p>Background: Humoral hypercalcemia of malignancy (HHM) is a paraneoplastic syndrome commonly associated with solid organ and hematological malignancies. Its occurrence in neuroendocrine tumors (NETs) is rare, with majority cases in pancreatic NETs. Here, we describe an extremely rare case of a metastatic duodenal NET presenting with severe hypercalcemia due to the secretion of Parathyroid Hormone-related Protein (PTHrP). This case features an exceptionally high PTHrP level, making it one of the most severe reported cases of NET-associated HHM. Case Presentation: A 70-year-old Indian male with hypertension and diabetes mellitus was found to have a well-differentiated Duodenal NET (grade 2, Ki67 index: 18.2%; T2N1M0). He underwent distal gastrectomy with D1 duodenal resection. Subsequent disease progression with hepatic and peripancreatic nodal metastases was managed with octreotide injections, Everolimus and Lutetium177 DOTATATE PRRT (Peptide receptor radionuclide therapy). Six months later, he presented with acute unresponsiveness and severe hypercalcemia (corrected calcium: 14.06 mg/dL) with suppressed iPTH levels (Intact Parathyroid Hormone) and markedly elevated PTHrP levels of 252 pmol/L (Parathyroid Hormone related Peptide), thereby confirming HHM. Multiple myeloma and osteolytic bone metastasis were excluded. Despite management with intravenous fluids, calcitonin, ibandronate, and multiple hemodialysis sessions, the patient succumbed to hypoxic brain injury. Discussion: We report a rare case of metastatic duodenal NET causing severe hypercalcemia due to excessive PTHrP production. With a remarkably elevated PTHrP level, this case is one amongst the most severe documented cases. The relationship between tumour grade and PTHrP production along with the refractory nature of the hypercalcemia, highlights the complex pathophysiology of this condition. Conclusion: PTHrP-mediated humoral hypercalcemia is an uncommon but life-threatening complication of duodenal NETs and is associated with adverse outcomes. Early recognition of this paraneoplastic syndrome, prompt metabolic correction, and timely escalation of NET-directed therapies, including consideration of PRRT, are crucial to improving clinical outcomes in patients with aggressive, receptor-positive disease.</ns3:p>