# Shift in secretory profile of a pNET: from indolent glucagonoma to aggressive insulinoma – a case report

## TL;DR

A patient with a pancreatic tumor changed from a slow-growing to an aggressive form, causing severe hypoglycemia that was hard to treat.

## Contribution

This case highlights the rare phenomenon of pNETs changing their hormone profile and the challenges in managing such shifts.

## Key findings

- The patient's tumor shifted from glucagonoma to insulinoma after 14 years.
- Current treatments failed to control severe hypoglycemia caused by insulin hypersecretion.
- Alpha-emitting radiopharmaceuticals may offer better control for advanced insulin-secreting pNETs.

## Abstract

Pancreatic neuroendocrine tumors (pNETs) can change their hormonal profile over time, leading to new clinical syndromes that significantly impact prognosis and management. We report the case of a patient with a metastatic glucagon-secreting pNET who, after 14 years of disease and multiple treatment lines, developed insulin hypersecretion and severe, treatment-refractory hypoglycemia. Despite several strategies, including diazoxide, somatostatin analogues, glucocorticoids, everolimus, peptide receptor radionuclide therapy, and continuous glucose and glucagon infusions, glycemic control was not achieved, and the patient ultimately died from treatment complications. This case highlights the clinical challenges of managing metachronous hormonal syndromes and the importance of long-term endocrine follow-up in pNET patients. It also emphasizes the limitations of current therapeutic strategies and the urgent need for new treatment options, including alpha-emitting radiopharmaceuticals, which may offer improved disease and symptom control in advanced, insulin-secreting pNETs.