NESIDIOBLASTOSIS AND PERSISTENT NEONATAL HYPERINSULINISM

Neonatal hyperinsulinism is characterized by severe hypoglycaemia whic h can cause serious neurologic effects. Pancreatic morphological abnor malities involve either focal or diffuse lesions. The former can be cu red by resection, whereas the latter of uncertain pathogenesis, often require subtotal pancreatectomy. We investigated various hypotheses in an effort to explain the origin of this latter form of hyperinsulinis m. We determined that nesidioblastosis, long considered to be the basi c structural lesion of the diffuse form of hyperinsulinism, is not spe cific and does not correspond to a continuous proliferation of endocri ne cells. We found that an increase in beta-cell mass can be excluded since the volume density of beta cells is not systematically higher in hyperinsulinemic infants than in controls. The hypothesis of a decrea se in D cells is attractive but should be considered with due caution since the decrease of the D-cell volume density observed in hypoglycae mic infants is inconstant. Finally, the notion of beta-cell functional abnormality seems the most likely explanation since a higher quantity of proinsulin was detected within the Golgi area by a specific antibo dy and abnormal nuclei with abundant cytoplasm were observed in some c ells. These histological abnormalities can be observed during intraope rative morphological examination. Functional activity might also be ev aluated by studying the messenger RNA of proinsulin.