Nesidioblastosis: An Old Term and a New Understanding

Nesidioblastosis is a clinically, pathologically, and genetically heterogeneous disease. Differences between well described forms in neonates with persistent hyperinsulinemic hypoglycemia of infancy (PHHI) and rare forms in adults are described. Histopathologic criteria include hypertrophic islets occasionally showing beta cells with pleomorphic nuclei, ductuloinsular complexes, and neoformation of islets from ducts. These changes can be found as diffuse or focal forms of nesidioblastosis. Although most cases occur sporadically, several genetic defects (SUR1, Kir6.2, GCK, and GLUD1 genes) have been described in neonates. In adults a higher rate of nesidioblastosis is observed in conjunction with multiple endocrine neoplasia type 1. The disease is diagnosed biochemically by a supervised fasting test in adults and in neonates by determining the glucose requirements to maintain normoglycemia, inappropriately high insulin and c-peptide levels, low free fatty acid and ketone body concentrations, glycemic response to glucagons, and the absence of ketonuria. If all highly selective noninvasive imaging techniques fail to identify a tumor, selective arterial calcium stimulation testing for gradient-guided surgery in adults and percutaneous transhepatic pancreatic venous sampling in neonates should be performed. a 95% pancreatectomy is necessary in neonates with a diffuse form of nesidioblastosis, whereas focal forms can be treated by partial pancreatectomy.