Case Report: Recurrent hypoglycemia due to graft-derived insulinoma in a patient with type 1 diabetes following pancreas-kidney transplantation.

Hypoglycemia is a frequent finding after simultaneous pancreas-kidney (SPK) transplantation, but its etiology is often multifactorial and challenging to interpret. We report a rare case of late-onset severe hypoglycemia secondary to a neuroendocrine tumor arising in a pancreatic allograft. A 60-year-old man with type 1 diabetes mellitus underwent SPK transplantation in 2007 with immediate graft function and long-term metabolic stability. Ten years post-transplant, partial pancreatic graft dysfunction and progressive vascular complications were noted. In 2024, 17 years after transplantation, the patient developed recurrent, documented hypoglycemic episodes despite withdrawal of glucose-lowering therapy, with fasting plasma glucose values as low as 40 mg/dL and a marked reduction in HbA1c. Biochemical evaluation suggested endogenous hyperinsulinism, with elevated chromogranin A levels. Imaging studies revealed a large hypervascular mass within the pancreatic graft, with high somatostatin receptor expression on 68Ga-DOTA-TOC PET-CT. Histology from biopsy and subsequent total graft pancreatectomy confirmed a well-differentiated grade 2 neuroendocrine tumor with focal insulin expression, consistent with insulinoma. Surgical resection resulted in complete resolution of hypoglycemia. This case highlights the need to consider rare but clinically significant causes of hypoglycemia in SPK recipients and underscores the importance of a comprehensive, multidisciplinary diagnostic approach integrating continuous glucose monitoring, biochemical markers, and advanced imaging.