Remission of hypoglycemia after partial resection of a metastatic islet cell tumor

The course of a malignant islet cell tumor, producing increased levels of both insulin and glucagon, was studied clinically and in vitro for two years. The patient presented with hypoglycemia, and extensive hepatic metastases were present. Instead of biopsy alone, it was elected to remove the primary in the tail of the pancreas, and subtotal pancreatectomy was performed. There followed a six month interval without hypoglycemia, during which immunoreactive insulin (IRI) decreased (though remaining elevated) and immunoreactive glucagon (IRG) increased markedly. The tumor and a liver metastasis contained elevated IRI and IRG with immunofluorescence for insulin, though typical beta and alpha cells were not present on electron microscopy. A preparation of a monolayer culture of a liver metastasis decreased its IRI production with a similar time course to the clinical improvement, though rapid cell growth continued. Streptozotocin in vitro was markedly cytotoxic. In vivo Streptozotocin caused tumor regression, increase in fasting plasma glucose, decrease in plasma IRI and IRG, and improvement of glucose tolerance. Thus, this case showed elevated IRG in plasma and tumor, improvement in glucoregulation upon excision of the primary, and both in vitro cytotoxicity and clinical improvement with Streptozotocin. It is suggested (1) that cases refractory to therapy directed toward suppression of insulin secretion might benefit from removal of the primary and (2) that further use of cultures of such tumors should be initiated to establish whether they might be useful for predicting in vivo effectiveness of cytotoxic agents.