Two case reports of rare PTHrP-secreting pancreatic neuroendocrine tumors highlight how calcium levels can track disease progression and how treatment response varies dramatically between patients.
8 years of stable diseaseAchieved in one patient through multimodal peptide-based therapy, while the other patient with a similar tumor grade had a rapidly progressive course
What the researchers found
The two cases showed strikingly different outcomes despite similar tumor grades (WHO grade 2; Ki-67: 7% and 8%). Patient 1 (age 55) achieved eight years of stable disease with multimodal therapy including somatostatin analogues, PRRT, and chemotherapy, though she developed bilateral hip osteoarthrosis from prolonged high calcium. Patient 2 (age 34) had refractory hypercalcemia that responded only partially to zoledronate, high-dose denosumab, and maximal somatostatin therapy, and she succumbed to progressive disease. Calcium levels tracked reliably with disease activity in both cases.
Why it matters
PTHrP-secreting pancreatic neuroendocrine tumors are extremely rare, and there is no established treatment protocol. These cases provide real-world evidence on how peptide-based therapies like somatostatin analogues and PRRT perform in this context, and introduce the practical concept of using calcium as a readily available tumor marker — which could improve monitoring in similar rare cases.
How the study worked
This is a case report of two patients with metastatic, well-differentiated PTHrP-secreting pancreatic neuroendocrine tumors treated at a single center. The authors documented treatment timelines, calcium levels, imaging results, and clinical outcomes across multiple treatment modalities.
What this study cannot tell us
As a two-patient case report, this provides the lowest level of clinical evidence and cannot establish generalizable treatment guidelines. The contrasting outcomes could reflect numerous unmeasured factors. Treatment decisions were made clinically rather than following a standardized protocol, making it impossible to isolate the effect of any single therapy.
How to read the evidence
This is a case report of only two patients, representing the lowest tier of clinical evidence. While it provides valuable clinical detail for an extremely rare condition, findings cannot be generalized without larger studies.
When this study was published
Published in 2026, this represents current clinical practice and the latest thinking on managing these rare tumors with available peptide-based therapies.
The bigger picture
Neuroendocrine tumors that secrete peptide hormones like PTHrP represent a challenging intersection of oncology and endocrinology. As peptide receptor-targeted therapies like PRRT become more widely available, understanding which patients respond — and which develop refractory metabolic complications — is critical for optimizing individualized treatment. These cases add to the limited evidence base for this rare functional syndrome and highlight the need for international collaboration.
Questions still open
- What factors determine whether PTHrP-secreting pancreatic tumors respond to somatostatin analogues and PRRT versus becoming refractory?
- Could earlier aggressive calcium management prevent complications like the bilateral hip osteoarthrosis seen in the first patient?
- Would an international registry for these rare tumors help identify optimal treatment sequencing?
Common questions
What is PTHrP and why do some tumors secrete it?
What is peptide receptor radionuclide therapy (PRRT)?
Read the original research
Multimodal management of hormonal and oncological progression in PTHrP-secreting pancreatic neuroendocrine tumours.
Endocrine oncology (Bristol, England), 6(1), e250085
Citation
Zueva, Alexandra; Loh, Ee Wen; Masuka, Shamiso; Wadsley, Jonathan; Newell-Price, John; Munir, Alia. (2026). Multimodal management of hormonal and oncological progression in PTHrP-secreting pancreatic neuroendocrine tumours.. Endocrine oncology (Bristol, England), 6(1), e250085. https://doi.org/10.1530/EO-25-0085