Persistent Hyperinsulinemic Hypoglycemia in 15 Adults With Diffuse Nesidioblastosis

Abstract

Persistent hyperinsulinemic hypoglycemia (PHH) in adults that is not caused by an insulinoma is a rare and not well-characterized disease that has been named nesidioblastosis. In this study, we defined and scrutinized criteria for its histologic diagnosis, assessed its relative incidence, and discussed its pathogenesis. In pancreatic specimens from 15 adult patients with PHH in whom no insulinoma was detected and in 18 adult control patients, the endocrine tissue was screened for islet and beta-cell changes. The diagnostic reliability of the findings was checked by an interobserver analysis. The relative frequency of the disease was assessed in a series of 232 patients with PHH. Finally, genetic analysis of the menin gene was performed. Among the various indicators of islet changes, beta-cell hypertrophy characterized by enlarged and hyperchromatic beta-cell nuclei was the most significant and diagnostic finding in patients with PHH. The interobserver analysis revealed 100% specificity and 87.7% sensitivity. The hyperfunctional state of the beta-cells was not associated with changes in the subcellular distribution of insulin and proinsulin, proliferative activity, or mutations of the menin gene. Our results indicate that diffuse nesidioblastosis in adult patients with PHH resembles that seen in neonates suffering from PHH. The most important criterion for the diagnosis is the beta-cell hypertrophy. As approximately 4% of adult patients with PHH are affected by diffuse nesidioblastosis, this disease is not as rare as it has been thought to be. Pathogenetically, the defective insulin secretion could be based on a molecular defect.

Hyperinsulinemic Hypoglycemia After Gastric Bypass Surgery Is Not Accompanied by Islet Hyperplasia or Increased β-Cell Turnover

“…It was therefore proposed that the hyperinsulinemic hypoglycemia was likely secondary to this presumed excessive concentration of GLP-1 (5). In support, in vitro and animal studies reported that GLP-1 may increase ␤-cell replication and inhibit ␤-cell apoptosis (6,7), and it has been reported that GLP-1 concentrations are increased after GBS (8 -10).Hyperinsulinemic hypoglycemia has been reported both in infants (11,12) and more rarely in adults (13,14) in the absence of insulinoma. In infants, this condition was originally termed nesidioblastosis (15) as it was thought that the hyperinsulinemia arose as a consequence of increased islet formation from putative islet precursors adjacent to pancreatic ducts.…”

“…As a consequence, this syndrome was renamed persistent hyperinsulinemic hypoglycemia of infancy (17). Recent studies of pancreata of adults with hyperinsulinemic hypoglycemia in the absence of an insulinoma have revealed that the most striking abnormality is hyperplastic ␤-cells with enlarged nuclei, consistent with chronically increased insulin secretion, analogous to persistent hyperinsulinemic hypoglycemia of infancy (14).…”

“…Hyperinsulinemic hypoglycemia has been reported both in infants (11,12) and more rarely in adults (13,14) in the absence of insulinoma. In infants, this condition was originally termed nesidioblastosis (15) as it was thought that the hyperinsulinemia arose as a consequence of increased islet formation from putative islet precursors adjacent to pancreatic ducts.…”

Prolonged successful therapy for hyperinsulinaemic hypoglycaemia after gastric bypass: the pathophysiological role of GLP1 and its response to a somatostatin analogue

“…Histologically, these patients have islet enlargement, hypertrophic b-cells with enlarged hyperchromatic nuclei and abundant clear cytoplasm (17,20). The detailed histology of the six cases reported by Service et al was reanalysed subsequently using a different control group from autopsy specimens (7,17).…”

Well-Differentiated Pancreatic Tumor/Carcinoma: Insulinoma

“…Nesidioblastosis affects approximately 4% of adults with hyperinsulinemic hypoglycemia [9]. The role of imaging is first to detect and provide precise anatomical localization and second to stage the tumor prior to surgery.…”