Subtotal
pancreatectomy specimens from two adults with hyperinsulinemic
hypoglycemia and one adult with
watery diarrhea syndrome were investigated. All three specimens were originally diagnosed as "
nesidioblastosis"; none had a
neoplasm, and all patients were cured of their endocrine dysfunction by the
surgical procedure. Tissue samples were studied by light microscopy and light microscopic immunohistochemistry for
serotonin,
ACTH,
bombesin,
calcitonin,
gastrin,
glucagon,
insulin,
HPP,
somatostatin, and VIP. The results were compared with those obtained from the parallel study of ten adult pancreata obtained at autopsy from patients without
pancreatic disease or endocrine dysfunction. The total endocrine cell mass was not notably greater in the pancreata from patients with endocrine dysfunction than in the controls. Both groups had an estimated 95% of the endocrine cell population organized in islets while the remaining 5% was irregularly dispersed amidst the exocrine ducts and acini. Findings more conspicuous in patients with endocrine dysfunction but not absent in the controls included: large islets, islets with irregular contours and ragged edges, and large individual islet cells with abundant cytoplasm and bizarre nuclei. Immunoreactivity for
insulin,
glucagon, and
somatostatin was demonstrated in all cases; the ratio among these
hormones in the patients with endocrine dysfunction and in the controls was similar. In the patients with hyperinsulinemic
hypoglycemia, step sections sequentially stained for
insulin and
somatostatin showed a close topographic relationship between these cell types. In the patient with the
watery diarrhea syndrome, VIP immunoreactive cells were easily identified admixed with exocrine components; they were only rarely seen within islets. We suggest that the hyperinsulinemic
hypoglycemia in these adults was not due to simple quantitative abnormalities in total endocrine cell mass nor to its maldistribution nor to lack of topographic proximity between
insulin and somatostatin cells. We speculate that the syndrome may be based on still unknown derangements of insulin secretion, release, and/or its degradation. In the case of the
watery diarrhea syndrome, the readily identifiable VIP immunoreactive cells represent the emergence of a functional expression regarded as ectopic for the endocrine cells of the pancreas. We conclude that
nesidioblastosis per se cannot be viewed as the structural basis of these endocrine dysfunctions since many of its features were present in control pancreata lacking any such association.(ABSTRACT TRUNCATED AT 400 WORDS)