Symptoms & Subtypes: Functional vs. Non-Functional pNETs

When you are diagnosed with a [pancreatic neuroendocrine tumor (-1 “Understanding Your pNET Diagnosis”), one of the first things your medical team will determine is whether the tumor is functional or non-functional. This classification is based entirely on whether the tumor cells are overproducing hormones that cause specific symptoms in your body ^[1][2].

Functional vs. Non-Functional: The Key Difference

The “neuroendocrine” cells that make up these tumors are naturally designed to produce hormones. In a functional pNET, the tumor cells are “active” and pump out large amounts of a specific hormone, such as insulin or gastrin, into your bloodstream ^[1]. These excess hormones cause distinct “syndromes” or sets of symptoms that often lead to a diagnosis ^[3].

In contrast, a non-functional pNET (NF-pNET) either does not produce hormones at all or produces them in such small amounts that they don’t cause a noticeable syndrome ^[1]. These are actually the most common type, representing 50% to 91% of all cases ^[4][5]. Because they don’t cause hormonal symptoms, they are often discovered “incidentally”—meaning they are found by accident on a scan for something else, like a kidney stone or an injury ^[6].

Specific Functional Subtypes

If your tumor is functional, it is named after the specific hormone it produces. Each has its own unique “calling card” of symptoms:

• Insulinoma (Insulin): The most common functional pNET ^[7]. It overproduces insulin, causing hypoglycemia (dangerously low blood sugar). Patients often experience the Whipple Triad: symptoms like shakiness, confusion, or sweating; a documented low blood sugar level; and immediate relief after eating sugar ^[8][9].
• Gastrinoma (Gastrin): Produces excess gastrin, leading to Zollinger-Ellison Syndrome. This causes the stomach to make too much acid, resulting in severe, painful stomach ulcers and chronic diarrhea ^[10][11].
• Glucagonoma (Glucagon): Produces glucagon, often leading to the “4Ds” syndrome: Diabetes (high blood sugar), Dermatitis (a painful, migrating red rash called NME), Deep vein thrombosis (blood clots), and Depression or weight loss ^[12].
• VIPoma (Vasoactive Intestinal Peptide): Produces VIP, which leads to WDHA syndrome: Watery Diarrhea, Hypokalemia (low potassium), and Achlorhydria (low stomach acid) ^[11].
• Somatostatinoma (Somatostatin): An extremely rare tumor that produces somatostatin, which can cause a “shutdown” of digestive processes, leading to diabetes, gallstones, and oily stools (steatorrhea) ^[13].

Symptoms of Non-Functional Tumors

Because non-functional tumors don’t send out hormone signals, they are usually silent until they grow large enough to press on nearby organs. This is known as mass-effect ^[1][14]. Symptoms of mass-effect depend on where the tumor is located:

• Jaundice: If a tumor in the “head” of the pancreas presses on the bile duct, it can cause yellowing of the skin and eyes ^[14].
• Abdominal Pain: A large tumor can cause a deep, dull ache in the belly or back ^[14].
• Bowel Obstruction: If the tumor presses on the stomach or intestines, it can cause nausea, vomiting, or a feeling of being full very quickly ^[14].

Whether your tumor is functional or non-functional, the goal of your care team is the same: to use the best treatment options to manage the tumor itself while ensuring any symptoms—whether from hormones or mass-effect—are carefully controlled ^[15].