The juvenile human endocrine pancreas: normal v idiopathic hyperinsulinemic hypoglycemia

Subtotal pancreatectomy specimens from 11 pediatric patients with idiopathic hyperinsulinemic hypoglycemia (IHH) were studied by conventional light and electron microscopic methods and by morphometric methods applied to sections immunostained specifically for A, B, D, and PP cells. The results were compared with corresponding studies of pancreata obtained at autopsy of 31 infants and children without abnormalities in carbohydrate homeostasis. In the control tissue, the total volume density of islet cells in live born premature infants (n = 12) was about 20%, in live born term newborn infants (0 to 1 months, n = 9) between 17.5% and 20%, in infants (1 to 7 months, n = 5) about 10%, and in children (1.5 to 11 years, n = 5) about 7.5%. Endocrine tissue was as abundant in the body and head as in the tail of the pancreata. The contribution of PP cells to total islet cell mass increased with age, and for the relative contribution of PP cell compared with total pancreatic parenchyma it remained relatively constant, while that of A, B, and D cells decreased with age. A wide spectrum of islet cell aggregates was a normal feature of development in the control tissue, an observation accentuated by specific immunocytochemical staining. Islet cells of all types were present singly and in small clusters in pancreatic ductal structures and intimately related to acini; nesidioblastosis, therefore, is a feature of normal maturation of the pancreas. Seven of the 11 cases of IHH had pancreata that were morphologically and morphometrically normal for age. No anatomic basis for hyperinsulinism in these cases was apparent. Four pancreata from patients with IHH contained discrete foci of proliferation of islet cells of all types but in which B cells greatly predominated. We conclude that nesidioblastosis as a morphologic diagnosis cannot be viewed as the structural basis of endocrine dysfunction since it can be absent in IHH, or many of its features present in control pancreata.