Endocrine Abstracts

JOINT786

Introduction: Pancreatic neuroendocrine tumours (PNETs) have an annual incidence of less than 1 case per 100,000 people, with the majority being nonfunctional. PTHrP-secreting PNETs are particularly rare, with few cases reported globally. Hypercalcemia caused by PTHrPoma can be life-threatening and requires a multimodal and multidisciplinary approach for effective management. In such cases, calcium levels may serve as a reliable tumour marker, particularly when PTHrP assays are unavailable.

Case presentation: A55-year-old woman was diagnosed with an 8 cm pancreatic tumour, secreting PTHrP (2.2 pmol/l, normal range 0-1.8), with multiple liver and spleen metastases. The patient presented with cough and hypercalcemia (2.85 mmol/l) with a fully suppressed PTH. Imaging revealed a large pancreatic mass, and histology confirmed a neuroendocrine tumour (ENETS Grade 2, Ki67 7%). Initial treatment with somatostatin analogue (SSA) Sandostatin® LAR® led to excellent response and subsequent normocalcaemia. However, a side effect of extreme insomnia prompted a switch to Somatuline® Autogel®. Progression then led to treatment combination with Peptide Receptor Radionuclide Therapy (PRRT) with Lutathera®. After 4 cycles of PRRT, tumour shrinkage was observed and normalisation of calcium and PTH levels was achieved, although PTHrP assay was no longer available. The patient continued to experience insomnia with SSA, including during a trial of subcutaneous short-acting octreotide. Given her favourable response to PRRT, SSA therapy was eventually discontinued to improve her quality of life. Subsequent hypercalcaemia was poorly controlled with zoledronate and denosumab, leading to the rapid development of bilateral hip osteoarthrosis, requiring joint replacements. As the disease and hypercalcaemia progressed despite a re-trial of Somatuline® Autogel®, chemotherapy was initiated. The patient received 2 cycles of Capecitabine/Temozolomide by 8 years after her original presentation, resulting in a reduction of the primary tumour and liver metastases, along with normocalcaemia. Severe depression ensued, which was managed with citalopram and required a treatment break.

Conclusion: PTHrP-secreting PNETs are extremely rare and are associated with hypercalcaemia and increased mortality. Successful management often requires a combination of therapies, including SSAs, PRRT and chemotherapy, conferring tumour and calcium levels control and ultimately prolonging survival. This case highlights the importance of personalised management strategies for NETs, with calcium serving as a reliable tumour marker for disease monitoring and treatment assessment.