A case of multiple endocrine adenomata and polycystic kidneys is reported. Functioning adenomata of the parathyroids and pancreas were removed surgically and a pituitary adenoma was associated with galactorrhea and amenorrhea.
Serial plasma glucose and insulin determinations during sixteen months of observations confirmed the temporary efficacy of tumor resection and partial pancreatectomy for islet cell adenomata. The suspected presence of multiple pancreatic islet cell adenomata, not removed at surgery, was confirmed when hyperinsulinism and hypoglycemia returned several months postoperatively. With benzothiadiazine therapy, plasma glucose levels rose and insulin concentrations fell, suggesting that these drugs exert a diabetogenic effect primarily through inhibition of insulin secretion. This effect does not appear to be mediated through an adrenal mechanism since it was seen in spite of bilateral adrenalectomy in this patient.
Evidence is presented which conflicts with the usual explanation for diabetic glucose tolerance curve in patients with functioning islet cell adenomata. In vitro studies with apparently uninvolved pancreas slices revealed that insulin secretion was stimulated by increasing concentrations of glucose. Insulin release occurred in vivo following oral glucose. Portal venous plasma insulin levels fell markedly only after resection of the normal tail of the pancreas. These findings indicated that there was no suppression of insulin output from the apparently uninvolved pancreas by the hyperinsulinemia associated with the tumor. During glucose tolerance testing, hyperglycemia was associated with hyperinsulinemia, a finding which supports a peripheral insensitivity to insulin's hypoglycemic action as a probable mechanism for the diabetic glucose tolerance in this patient.
Finally, evidence is presented that apparently uninvolved pancreatic tissue responds in vitro to mannose, glucose, leucine and tolbutamide. The response to glucose can be blocked by 2-deoxyglucose, an agent which blocks the metabolism of glucose 6-phosphate.
These findings suggest that insulin release in man is related to glucose phosphorylation or some product of glucose 6-phosphate metabolism.
