Recurrence of Metastatic Pro-insulinoma Nearly 50 Years After Subtotal Pancreatectomy

Excerpt

The incidence of functional pancreatic neuroendocrine tumors (PNET) is reported at approximately four cases per one million persons [1]. Patients with insulin-producing PNETs classically present with Whipple’s triad consisting of hypoglycemic symptoms after fasting (neuroglycopenia and sympathetic stimulation), hypoglycemia at the time of the symptoms, and symptom relief with treatment of hypoglycemia or ingestion of food [2]. Pro-insulinomas are an exceedingly rare subtype of PNET producing the precursor form of insulin, of which only a handful has been reported in the literature [3‐7]. They may present in identical clinical fashion, as proinsulin has approximately 10% of the biological activity as mature insulin [8]. The diagnosis requires high clinical suspicion as standard testing for hypoglycemia (fasting serum glucose, insulin, and C-peptide) may miss hyperproinsulinemia, which presents with low or normal insulin levels [8]. Oral glucose tolerance test may aid in differentiating reactive hypoglycemia from an insulinoma and specific proinsulin level should be obtained. Although these tumors can metastasize, the course remains generally indolent, and recurrence has been reported as low as 3 to 16% [9‐11]. Recent targeted therapeutic agents have opened the door for alternative treatment options in patients with advanced well-differentiated tumors, particularly those whose metastatic hormonally active tumors were unresectable [12‐14]. …