Simron Singh, MD: So Jon, we talked a bit about the patients who present with functional NETs [neuroendocrine tumors] or symptoms. What are some of the hormones that cause the symptoms you see in patients with neuroendocrine cancer?

Jonathan R. Strosberg, MD: The most common syndrome, by far, is carcinoid syndrome. A bunch of vasoactive factors are involved, but serotonin is the most prominent hormone. We think serotonin is directly responsible for diarrhea. It may be partially responsible for the flushing that patients experience, and it’s probably the main factor behind carcinoid heart disease, which causes damage primarily to the right-sided heart valves—tricuspid and pulmonary. But there are other vasoactive substances such as prostaglandins, bradykinins, tachykinins, etc.

Then there are the rarer hormonal syndromes that are primarily associated with pancreatic NETs. Insulinomas, of course, produce insulin or proinsulin, leading to episodes of hypoglycemia. Gastrinomas produce gastrin, leading to Zollinger-Ellison syndrome, a high-acid state. Most physicians expect to see heartburn and ulcers as a consequence of that, but it’s important to recognize that diarrhea is also an important symptom associated with gastrinomas. Of course, nowadays with proton pump inhibitors [PPIs], the diagnosis of Zollinger-Ellison syndrome is often delayed for many years and could be masked because PPIs are so effective.

Then there are the ultrarare syndromes such as VIPomas, which produce VIP [vasoactive intestinal peptide] and can result in severe watery diarrhea and electrolyte abnormalities. And glucagonomas can cause weight loss, cachexia, an unusual rash called necrolytic migratory erythema, and hyperglycemia. Those are really quite unusual.

Pancreatic NETs and lung NETs can cause ectopic Cushing syndrome. Others can produce PTH [parathyroid hormone] or PTHrP [parathyroid hormone-related peptide], leading to hypercalcemia. So the number of potential hormones is actually quite large.

Simron Singh, MD: So it makes it clear that we have to take a really good history and listen to our patients.

Jonathan R. Strosberg, MD: Absolutely. What are your thoughts on quality of life in patients with functional NETs versus nonfunctional NETs?

Simron Singh, MD: I think in patients who have functional NETs and are symptomatic from the different hormones—primarily serotonin—this can really impact a person’s life. Diarrhea can be debilitating. It can prevent normal mobility. It can prevent a person from working or from enjoying quality of life. I recently had a patient who was really affected by the fact that he couldn’t go watch his son’s hockey games because he was always afraid that he wouldn’t be able to get to the bathroom in time.

Jonathan R. Strosberg, MD: That could definitely be an issue.

Simron Singh, MD: That definitely affected his quality of life. We have to take this very seriously and be aggressive with treatment. We want to ensure that our patients can go on with a normal life as best as possible, given the constraints of the disease.

Jonathan R. Strosberg, MD: Right.

Transcript Edited for Clarity