Parathyroid Hormone-Related Peptide-Secreting Pancreatic Neuroendocrine Tumours: Case Series and Literature Review

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-α. 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.

Paraneoplastic syndromes secondary to neuroendocrine tumours

“…The first case of a PTHrP-producing malignant NET was described in a pancreatic islet cell tumour presenting with severe hypercalcaemia during pregnancy (Abraham et al 2002); however, benign phaeochromocytomas can also secrete PTHrP and cause hypercalcaemia (Fukumoto et al 1991). Several reports have now demonstrated either biochemical and/or immunohistochemical PTHrP-related hypercalcaemia in w25 patients with PICTs (Mao et al 1995, Srirajaskanthan et al 2009). The majority of these tumours are well-differentiated stage III-IV carcinomas, and this entity should be considered in the differential diagnosis of all patients with NETs presenting with hypercalcaemia and a disproportionately low PTH.…”

“…The majority of these tumours are well-differentiated stage III-IV carcinomas, and this entity should be considered in the differential diagnosis of all patients with NETs presenting with hypercalcaemia and a disproportionately low PTH. In contrast to other PTHrP-secreting malignancies that have a mostly abysmal prognosis, patients with NET-related PTHrP secretion have a much better outcome (DeLellis & Xia 2003, Srirajaskanthan et al 2009). It is possible that the exact prevalence of PTHrP-secreting NETs may well be underestimated as the assay is difficult to perform, and may not always be requested (Srirajaskanthan et al 2009).…”

“…In contrast to other PTHrP-secreting malignancies that have a mostly abysmal prognosis, patients with NET-related PTHrP secretion have a much better outcome (DeLellis & Xia 2003, Srirajaskanthan et al 2009). It is possible that the exact prevalence of PTHrP-secreting NETs may well be underestimated as the assay is difficult to perform, and may not always be requested (Srirajaskanthan et al 2009). Very few cases of ectopic PTH secretion from NETs have been documented, two from an SCLC and one from an MTC (Weiss et al 2006, Demura et al 2009.…”

Nowotwory neuroendokrynne trzustki — zasady postępowania (rekomendowane przez Polską Sieć Guzów Neuroendokrynnych)

“…SSA have been proven effective in controlling hypercalcaemia associated with the hypersecretion of the parathyroid hormone-related peptide (PTHrP) in rare PNENs secreting PTHrH [126].…”

Immunolocalization of PTHrP in the parotid glands of three rodents species: Clethrionomys glareoulus, Microtus arvalis and white Swiss mice.

“…In the course of neoplastic disease, PTHrP causes hypercalcemia, hypophosphatemia and elevated cAMP values in urine [1][2][3]. The human PTHrP gene occurs on the short arm of chromosome 12 and consists of nine exons [4].…”