GLP1 and glucagon co-secreting pancreatic neuroendocrine tumor presenting as hypoglycemia after gastric bypass

Abstract

Post-prandial hypoglycemia is frequently found after bariatric surgery. Although rare, pancreatic neuroendocrine tumors (pNET), which occasionally are mixed hormone secreting, can lead to atypical clinical manifestations, including reactive hypoglycemia. Two years after gastric bypass surgery for the treatment of severe obesity, a 54-year-old female with previous type 2 diabetes, developed post-prandial sweating, fainting and hypoglycemic episodes, which eventually led to the finding by ultrasound of a 1.8-cm solid mass in the pancreatic head. The 72-h fast test and the plasma chromogranin A levels were normal but octreotide scintigraphy showed a single focus of abnormal radiotracer uptake at the site of the nodule. There were no other clinical signs of hormone secreting pNET and gastrointestinal hormone measurements were not performed. The patient underwent surgical enucleation with complete remission of the hypoglycemic episodes. Histopathology revealed a well-differentiated neuroendocrine carcinoma with low-grade malignancy with positive chromogranin A and glucagon immunostaining. An extract of the resected tumor contained a high concentration of glucagon (26.707 pmol/g tissue), in addition to traces of GLP1 (471 pmol/g), insulin (139 pmol/g) and somatostatin (23 pmol/g). This is the first report of a GLP1 and glucagon co-secreting pNET presenting as hypoglycemia after gastric bypass surgery. Although pNET are rare, they should be considered in the differential diagnosis of the clinical approach to the post-bariatric surgery hypoglycemia patient.

Learning points: pNETs can be multihormonal-secreting, leading to atypical clinical manifestations.Reactive hypoglycemic episodes are frequent after gastric bypass.pNETs should be considered in the differential diagnosis of hypoglycemia after bariatric surgery.

Figure 1

Abdominal CT scan revealing a 1.8-cm solid mass in the pancreatic head (white arrow) (A); octreotide scan showing a focus of abnormal uptake of the radiotracer in the same topography of the pancreatic lesion without other foci of abnormal uptake of the radiotracer (B).

Figure 2

Photographs of histological findings of the hematoxylin eosin staining of the pNET (100×) (A) and surrounding normal pancreatic tissue on the top left corner (100×) (B); graphic illustration of tumor extract tissue concentrations (pmol/g tissue) of glucagon, GLP1, somatostatin and insulin (mean±s.d. of technical replicates) (C); immunostaining of the glucagonoma for the neuroendocrine markers chromogranin A (200×) (D), glucagon (200×) (E), GLP1 (F) and insulin (200×) (G); the proliferation index displayed by the low Ki-67 staining (200×) (H) (immune staining in brown).