Natural History of a Proinsulin-Secreting Insulinoma: From Symptomatic Hypoglycemia to Clinical Diabetes

Abstract

Insulinoma, an islet cell tumor of the pancreas, is clinically characterized by symptomatic hypoglycemia, an inappropriately increased plasma insulin level, and an increased proinsulin concentration. Current imaging and surgical techniques usually permit localization and resection of these mostly benign islet cell tumors with resolution of hypoglycemic symptoms. The association of diabetes mellitus and insulinoma is extremely rare. It has been reported in diabetic patients whose hypoglycemic symptoms or high circulating insulin levels were ultimately explained by the discovery of an insulinoma (1–4). Here, we describe a patient with a most unusual 24-yr history of a benign proinsulin-secreting insulinoma that initially caused classical hypoglycemic symptoms and then changed over time to the development of clinical diabetes. In 1976, a 47-yr-old white man without a prior history of endocrinopathy presented to the Clinical Center of the NIH for evaluation of a presumed insulinoma. He had no family history of endocrinopathy or diabetes. Eighteen months previously the patient had experienced an episode of hunger, diaphoresis, nervousness, and palpitations during a religious fast. These symptoms became more frequent over time and were typically relieved with food. Insulinoma was suspected on the basis of fasting hypoglycemia and inappropriately high insulin levels. In 1975, the patient underwent an exploratory laparotomy. However, the tumor could not be found, and a distal pancreatectomy and splenectomy were performed. Postoperatively, hyperinsulinemia and symptomatic hypoglycemia persisted. The patient was subsequently referred to the NIH.