Endocrine Abstracts

Introduction: Insulinoma is the most frequent functional endocrine tumor of the pancreas but remains rare with an incidence of less than 5 cases by million and by year. It is often sporadic but can occur in the context of MEN1 in about 5% of cases, being then readily multiple. Clinically, it is typically responsible for fasting hypoglycemic episodes. Only one case of multiple insulinomas, with no obvious argument for MEN1 context, has previously been reported (Babic an al., JCEM, 2016).

Methods: We report two cases of multiple insulinomas with atypical clinical and biological presentation, occurring outside the context of MEN1. The first case was a man, 51 years old and the second case, a woman, 69 years old. Both patients reported post-prandial hypoglycemic episodes and experienced severe hypoglycemia following glucose charge, respectively 0.8 mmol/l after intravenous glucose load in the first case and 2 mmol/l after oral glucose charge in the second case, with concomitant elevated insulin, respectively 157.6 mUI/l and 28.2 mUI/l. More expectedly, both cases also displayed at least one hypoglycemic episode during fasting trial, always associated with inadequate insulin and C-peptide levels, confirming the existence of an endogenous hyperinsulinism. Pancreatic imaging (MRI or CT) identified 4 lesions in the caudal region of the pancreas in both patients, ranging from 3.5 to 12 mm in the first case -2 of them being confirmed by octreoscan- and ranging from 8 to 30 mm in the second case-all harboring intense signal on TEP-DOTATOC (negative octreoscan). Histology confirmed the presence of 4 neuroendocrine benign tumors in both cases, respectively all and three of them being positive for insulin staining. No mutation in MEN1 gene or in genes involved in hyperinsulinism including ABCC8, KCNJ11, GCK, HNF4A and HNF1A was identified in the first case while MEN1 gene analysis is still in progress for the second case (very unlikely diagnosis).

Conclusion: We describe here a new entity of non-syndromic multiple insulinomas. Symptoms begin after the age of 50 years old, consisting in hypoglycemic seizures, unusually post-prandial. Glucose charge, stimulating inadequate insulin secretion, reproduces severe hypoglycemia. Organic substratum consists in lesions, localized in pancreas tail and positive in molecular imaging based on somatostatin receptors expression. The search for a molecular alteration might give clue to this new entity.