Parathyroid hormone-related peptide (PTHrP)-secreting pancreatic neuroendocrine tumours (Pan-NETs) are a rare cause of humoural hypercalcaemia of malignancy (HCM). We report two contrasting cases of metastatic well-differentiated PTHrP-secreting Pan-NETs (WHO grade 2; Ki-67: 7 and 8%, respectively), highlighting the variability in disease progression, response to multiple treatment modalities, and long-term outcomes. The first patient, a 55-year-old woman with mild hypercalcaemia who was largely asymptomatic except for a persistent dry cough at presentation, achieved stable disease control following eight years of treatment with somatostatin analogues (SSAs), peptide receptor radionuclide therapy (PRRT), and chemotherapy. During a prolonged period of uncontrolled hypercalcaemia prior to chemotherapy, she developed rapid bilateral hip osteoarthrosis and tumour calcification, a rare complication from long-standing calcium elevation. The second patient, a 34-year-old woman, had a more aggressive disease course, requiring multiple hospital admissions for refractory moderate-to-severe hypercalcaemia and variceal bleeding. Despite initial tumour stabilisation following PRRT, she developed refractory hypercalcaemia, demonstrating only partial response to zoledronate, high-dose denosumab, and maximal somatostatin analogue therapy, and ultimately succumbed to progressive disease and metabolic deterioration. These cases underscore the heterogeneity of PTHrP-secreting Pan-NETs and the challenges in optimising treatment strategies, given the lack of data on the optimal sequencing of therapies. Notably, calcium can serve as a reliable tumour marker for disease control, with persistent severe hypercalcaemia being a potential prognostic factor of poor outcome in patients with PTHrP-related hypercalcaemia. International collaboration and knowledge exchange are needed to ascertain the most effective management of this rare functional syndrome.
CORE (COnnecting REpositories)
CORE (COnnecting REpositories)