Parathyroid hormone-related peptide-secreting pancreatic neuroendocrine tumours: case series and literature review

Neuroendocrinology. 2009;89(1):48-55. doi: 10.1159/000151222. Epub 2008 Aug 5.

Abstract

Background/aims: Parathyroid hormone-related peptide (PTHrP) was discovered in 1987 as the tumour product responsible for humoral hypercalcaemia of malignancy (HHM). Pancreatic neuroendocrine tumours (NETs) are uncommon malignancies with an incidence of 1:100,000 population. PTHrP-secreting NETs are rare but are being recognised as a cause of HHM in NETs. We describe the largest series to date and the management of these rare tumours.

Methods: One male and 4 female patients were seen in our unit from 1998 to 2006. The average duration of follow-up was 86 months from initial diagnosis. All patients had a histologically confirmed diagnosis of pancreatic NET, all of which were low-grade tumours. PTHrP assay was performed in 4 of 5 cases and was elevated in these patients.

Results: Initial management involved surgery in 2 of 5 cases, whilst 2 cases underwent chemotherapy and 1 case was commenced on interferon-alpha. We discuss the further therapies that all patients underwent and the complexities that arose in managing disease progression as well as resistant hypercalcaemia.

Conclusion: PTHrP-secreting tumours should be considered in the differential diagnosis of patients with NETs who present with hypercalcaemia and a disproportionately low PTH. PTHrP tumours may well be underestimated as the assay is difficult to perform and may not be requested. In hypercalcaemic patients the standard management acutely includes intravenous fluids, diuretics and intravenous bisphosphonate. In the further management, somatostatin analogue therapy is the first medical option to consider and we discuss the role of other therapies.

Publication types

  • Review

MeSH terms

  • Adult
  • Diagnosis, Differential
  • Disease Progression
  • Female
  • Humans
  • Hypercalcemia / drug therapy
  • Hypercalcemia / etiology*
  • Male
  • Middle Aged
  • Neuroendocrine Tumors / complications
  • Neuroendocrine Tumors / diagnosis*
  • Neuroendocrine Tumors / metabolism*
  • Neuroendocrine Tumors / therapy
  • Pancreatic Neoplasms / diagnosis*
  • Pancreatic Neoplasms / metabolism*
  • Pancreatic Neoplasms / therapy
  • Parathyroid Hormone / metabolism
  • Parathyroid Hormone-Related Protein / metabolism*
  • Radionuclide Imaging

Substances

  • Parathyroid Hormone
  • Parathyroid Hormone-Related Protein