Pancreatic Endocrine Neoplasms Part 1

Pancreatic endocrine neoplasms, also known as “islet cell tumors” and “pancreatic neuroendocrine tumors,” account for only 2% of all of the tumors of the pancreas.  They are, however, very important to recognize because the prognosis and treatment of these distinctive tumors differs significantly from the prognosis and treatment of the more common “pancreatic cancer” (ductal adenocarcinoma of the pancreas).  This Blog, the first of three we’ve written on pancreatic endocrine neoplasms, will focus on syndromic (functional) pancreatic endocrine neoplasms.  That is, pancreatic endocrine neoplasms that produce a clinical syndrome.  In part 2 we will discuss non-syndromic pancreatic endocrine neoplasms that arise in patients without a family history of the disease.  In the third Blog in this series will focus on familial, or inherited, forms of pancreatic endocrine neoplasms.

Sporadic pancreatic endocrine neoplasms can be broadly divided into those that are “functional” or “syndromic,” and those that are “non-functional,” or “non-syndromic.”  As mentioned earlier, functional pancreatic endocrine neoplasms produce a clinical syndrome because they produce excessive amounts of hormones such as insulin, gastrin, glucagon or vasoactive intestinal peptide (VIP). 

Inulinomas are the most common syndromic pancreatic endocrine neoplasms .  Not surprisingly, insulinomas cause symptoms because they produce abnormal amounts of the hormone insulin.  Insulin normally helps control blood sugar levels, and insulinomas produce a low blood sugar (hypoglycemic) syndrome.  This syndrome is characterized by confusion, behavioral changes, blurred vision, and in severe cases coma and even death.  Surgical resection is the treatment of choice for insulinomas, and in most (90%) cases surgical resection is curative. 

Gastrinomas are syndromic pancreatic endocrine neoplasms which cause symptoms because they produce excessive amounts of the hormone gastrin.  Gastrin is a hormone that controls acid levels in the stomach.  Patients with a gastrinoma therefore develop stomach ulcers, symptoms of gastroesophageal reflux (heartburn), and diarrhea.  As will be discussed in the next Blog on pancreatic endocrine neoplasms, some gastrinomas arise in patients with the familial MEN-1 syndrome.  The ten year survival rate for patients with gastrinomas is ~50%.

Glucagonomas are syndromic pancreatic endocrine neoplasms which cause symptoms because they produce excessive amounts of the hormone, you guessed it, glucagon.  Glucagon normally functions to raise blood sugar levels, and patients with a glucagonoma typically develop the four “D’s.” 1) Diabetes (high blood sugar levels), 2) deep venous thromboses (blood clots), depression, and dermatitis (skin rash).  The rash is distinctive, and is called necrolytic erythema migrans. Glucagonomas can be very aggressive tumors, and more than 50% of patients have liver metastases at the time they are diagnosed.

VIPomas are syndromic pancreatic endocrine neoplasms which cause symptoms because they produce excessive amounts of the hormone VIP (vasoactive intestinal peptide).  VIPomas release excess amounts of the hormone VIP and patients develop “Werner-Morrison syndrome” with watery diarrhea, low blood potassium levels (hypokalemia), and low blood chloride levels (hypochlorhydria).  About half  of surgical patients with VIPoma are cured after their tumor is resected.

Somatostatinomas, the last of the syndromic or functional tumors we will discuss,  are syndromic pancreatic endocrine neoplasms which cause symptoms because they produce excessive amounts of the hormone somatostatin.  These are very rare tumors.  Patients with somatostatinomas often develop diabetes mellitus, diarrhea, anemia (low red blood cell count), and gallstones.  The survival rate is only ~60%. 

Thus we can see that there are a number of different syndromic pancreatic endocrine neoplasms, each of  which cause their own distinctive set of symptoms.  In addition, each of these syndromic pancreatic endocrine neoplasms carries its own prognosis.  For example, patients with insulinomas tend to have an excellent prognosis, while patients with glucagonomas have a poor prognosis. 

In part 2 of this Blog series we will discuss non-syndromic pancreatic endocrine neoplasms that arise in patients without a family history of the disease.