Parathyroid Hormone- Related Peptide Secretion From a Pancreatic Neuroendocrine Tumor: A Rare Case Report of Severe Hypercalcemia

Background/Objective: Hypercalcemia is a common occurrence associated with malignancy, due to a number of causes: (1) lytic bone metastases, (2) production of 1,25-dihydroxyvitamin D from lymphoma, and (3) parathyroid hormone-related peptide (PTHrP) secretion usually from solid tumors. Case Report: A 56-year-old woman presented with symptoms of severe hypercalcemia. Investigations determined that this was due to PTHrP secretion from a pancreatic neuroendocrine tumor (pNET), a noted complication in 1.1% of pNET cases. Although un fit for curative therapy, the patient was treated with fluid replacement, bisphosphonates, calcitonin, and denosumab. After treatment, she had recurrent severe symptomatic hypercalcemia on several occasions despite adjunctive therapy with a somatostatin analog. Ultimately, the patient died as a result of refractory hypercalcemia. Discussion: The hypercalcemia that is rarely associated with PTHrP secretion from pNETs is aggressive and often refractory to the usual medical treatment of hypercalcemia of malignancy. Effective treatment requires cytoreduction of the causative tumor. Denosumab, a receptor activator of nuclear factor kappa beta ligand inhibitor, has proven useful in some cases. Conclusion: This challenging case highlighted the rare but potentially fatal association of pNET with hypercalcemia. Hypercalcemia was the main cause of mortality in an otherwise relatively indolent malignancy. (c) 2024 AACE. Published by Elsevier Inc. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).