Acute Encephalopathy and Severe Hypercalcemia as the Initial Presentation of a Large Parathyroid Hormone-Related Protein (PTHrP)-Secreting Pancreatic Neuroendocrine Tumor: A Case Report

Pancreatic neuroendocrine tumors (pNETs) are rare neoplasms that present with diverse clinical manifestations depending on their secretory activity. Paraneoplastic hypercalcemia due to parathyroid hormone-related peptide (PTHrP) secretion by pNETs is an uncommon but serious complication. We describe the case of a 67-year-old female with a past medical history of multiple sclerosis and uveitis presenting with acute metabolic encephalopathy due to profound hypercalcemia. Laboratory workup revealed a corrected calcium of 22.4 mg/dL and PTHrP of 327 pg/mL. Imaging demonstrated a new 15 cm pancreatic mass with adrenal nodules suspicious for metastatic disease. Pathology from a percutaneous biopsy confirmed a well-differentiated pNET with a Ki-67 index of ~15%. The patient's mental status improved following treatment of hypercalcemia with intravenous hydration, calcitonin, zoledronic acid, and urgent hemodialysis. She was started on lanreotide therapy for pNET treatment. This case highlights the importance of considering pNETs in the differential diagnosis of unexplained hypercalcemia, as timely recognition and management can reverse neurologic dysfunction and improve outcomes. Awareness of this rare presentation may facilitate earlier diagnosis and treatment of underlying neuroendocrine malignancies.