Dr. Michael Morse provides an overview of neuroendocrine tumors and defines “carcinoid tumor,” “carcinoid syndrome” and “carcinoid crisis.”
PUBLISHED October 27, 2017
Shubham Pant, MD: The first thing people say when people hear “tumor” is, “Oh my God, I’m going to die, this is a tumor.” But tell me, as a doctor who treats neuroendocrine tumors, there can be different types of neuroendocrine tumors, isn’t that right?
Michael A. Morse, MD: Right. Well, first of all, the name “endocrine” is a broad term and there are many different types of cancers that fit under that. The type of tumor that most people are thinking of is one that typically starts in the GI tract, although it can start in the lungs as well. It generally grows silently for a long time and eventually can spread to regional lymph nodes or spread to the liver. And those particular ones that start in the GI tract, we often call those “carcinoid,” although the proper terms now would be a neuroendocrine tumor of the small bowel.
Shubham Pant, MD: What other places can it happen? Like small bowel is one place, where else?
Michael A. Morse, MD: The tumors that we call “neuroendocrine” broadly can start in the lungs and in the GI tract. There are some unusual locations, they’re rare, but almost any location in the body technically could have them. And then there are some other cancers that we’re really not talking about today that do fit under the title of neuroendocrine—pheochromocytomas that can start in the adrenal gland, for example, are a type of neuroendocrine tumor.
Shubham Pant, MD: And what do you tell your patients, Dr. Morse? What do you say about this long-term disease that you’ll have to live with it? What do you tell a patient?
Michael A. Morse, MD: The first thing is to be able to make sure people have the expectations that I think they should have for a long-term illness like this. Many people do want to be aggressive, do everything possible right now—every treatment they’ve read about—to get rid of the cancer. And, of course, if it’s possible to eradicate it, we’ll certainly do that. But in the majority of cases, it is going to be a long-term, treat it when you need to, over time. And so, I actually spend a lot of time on trying to explain that because it’s more like a marathon. We want to use the least toxic therapies, things that can help people with their quality of life but don’t impair their quality of life, and many of the therapies people have heard about are the ones that we discussed that we may eventually use. In fact, in many cases, we use all of the different therapies that are available, but there’s a right time and place for them. And, generally after, sometimes it’s more than one visit, but people realize that it’s OK to take a step back, be comfortable with the idea of starting to manage it, and take each step as it comes instead of trying to plan out the entire next many years of life.
Shubham Pant, MD: So, there are certain different terminologies that are used: carcinoid tumor, carcinoid syndrome, carcinoid crisis—different tumors. Let’s start from the beginning. What’s the difference between carcinoid tumor and carcinoid syndrome? Is it one and the same thing? Did Larry have a carcinoid tumor or did he have a carcinoid syndrome, or did he have both?
Michael A. Morse, MD: The definition of the pathologic entity would be, technically speaking, a neuroendocrine tumor. That’s the terminology we’re trying to use now broadly. However, many people still understand these as carcinoids. So, we can talk about it as a carcinoid. That’s the name of the cancer.
Shubham Pant, MD: The name of the cancer. It’s a biopsy, you have a neuroendocrine tumor of the GI tract.
Michael A. Morse, MD: Correct. And also, for the rare cases where people have a neuroendocrine carcinoma—which is a more aggressive, more rapidly growing form—we try to distinguish that. But most people have the lower grade tumors…
Shubham Pant, MD: Well-differentiated tumor.
Michael A. Morse, MD: The well-differentiated, exactly. So, we’ll call those carcinoids. And the syndrome is a set of signs and symptoms that people have, in some cases if they have an underlying carcinoid tumor. It’s important to realize that not everybody who has a carcinoid tumor will have carcinoid syndrome. But in somebody who has the tumor and it secretes, predominantly serotonin, there are a series of signs and symptoms, the most common would be diarrhea and flushing. Some people also have wheezing.
Shubham Pant, MD: Again, serotonin is a hormone that is secreted?
Michael A. Morse, MD: These tumors make many different hormones. The predominant one that we generally talk the most about, and the one that seems to cause a lot of the symptomatology, is serotonin.
Shubham Pant, MD: And can you measure it in the blood? Like can somebody go and get a blood test for serotonin?
Michael A. Morse, MD: You can measure serotonin.
Shubham Pant, MD: Is it useful?
Michael A. Morse, MD: Serotonin, first of all, can be made in somewhat of a pulsatile manner. So, it’s possible that if you just do a random sample, it could be near normal. It’s also stored in platelets and so if there are some issues about how it’s drawn. Also, of course, the diet can affect it if there is serotonin in some foods. What we prefer, if we’re going to try to get some idea of the amount of serotonin made in a day, is to do a 24-hour urine collection for 5-HIAA, which is a breakdown product of serotonin. So, despite there being spikes during the day, you’re collecting, over an entire 24-hour period, the 5-HIAA so it smooths out a lot of those peaks; it’s a more useful number. It’s now possible also to measure 5-HIAA in the serum, which is, for some people, more convenient because carrying the jug around can be…
Shubham Pant, MD: That’s a collection; that sounds like a tall order. You said some people get it, some people don’t. What percentage of patients with carcinoid tumors or neuroendocrine tumors are well-differentiated, have a carcinoid syndrome?
Michael A. Morse, MD: It really depends in part on the stage. People with localized tumors, if it’s just in the GI tract or spread to regional lymph nodes, typically won’t have carcinoid syndrome because the serotonin and any of the other peptide hormones made by these tumors are generally cleared in the liver. Once somebody has liver metastasis or if they have…
Shubham Pant, MD: That means cancer in the liver, liver metastases.
Michael A. Morse, MD: Correct. If they have spread of the tumor to the liver or if they start out with a pulmonary carcinoid, then they have exposure of the systemic circulation to the serotonin, and so they’ll be symptomatic. Also, there’s some correlation with tumor bulk if somebody with the largest amount of metastatic disease is more likely to have the symptoms. I’ve also noticed that sometimes people just experience it differently and they don’t always equate the symptoms with the serotonin. There are some people who don’t notice that they flush, for example. Their family members will say, “Oh, you flush all the time,” but they don’t seem to notice. Other people, and I think you’ll probably talk about this later, the flushing does cause some real symptoms for them, something that’s really noticeable.
Shubham Pant, MD: Larry, tell us about what kind of symptoms you had. And I’m guessing, Dr. Morse, Larry had carcinoid syndrome along with carcinoid tumor.
Michael A. Morse, MD: Correct.
Shubham Pant, MD: Because he had flushing. So, flushing is one of them. What other symptoms did you have?
Larry Pleasant: I had flushing. The thing I neglected to mention at the beginning is that by the time my tumors were diagnosed, they had already spread to my liver. So, surgery was ruled out as an option for the treatment. But the flushing I had was, in some instances, intense enough to create nausea, vomiting, chest pain, sweating, and absolute loss of energy for several hours. In other cases, the flushing was fairly mild. Accompanying the flushing, I had pretty significant diarrhea.
Shubham Pant, MD: And when did that start? Because you said in the beginning, flushing was the number one.
Larry Pleasant: Right.
Shubham Pant, MD: When did the diarrhea start?
Larry Pleasant: The diarrhea didn’t start until well after I had been diagnosed and was already in treatment. I didn’t have the diarrhea in the beginning. That started sometime later, months later.
Shubham Pant, MD: And is that common, Dr. Morse, for the diarrhea to start months later, or is it mostly when you get a treatment, can another symptom show up?
Michael A. Morse, MD: Different people seem to manifest the symptoms in different ways. We know that there are probably different hormones that account for some of the symptoms. Serotonin is very well linked to the diarrhea. It’s also important to realize that there could be many causes of diarrhea in somebody who has a tumor that starts in their GI tract. It’s not always carcinoid syndrome. The flushing seems to be less related to serotonin and to some other hormones. So, it’s possible for somebody to have a tumor that makes more of those hormones that lead to flushing and less of the serotonin production. But it’s very common to have both of them, to tell you the truth.
Shubham Pant, MD: So, to recap, with carcinoid tumors, or endocrine tumors, some of them can have carcinoid syndrome, some of them may not. And then the third thing, which we are going to talk about, is carcinoid crisis. So, what is a carcinoid crisis?
Michael A. Morse, MD: In many ways, it’s an extreme episode of having carcinoid syndrome. It’s when large amounts of serotonin, and probably some of the other hormones made by these tumors, are released suddenly in response to a stimulus. The one we are most concerned about is surgery—the events that happen during anesthesia and surgical manipulation. And even if one, for example, manipulates the part of the body that has the tumor, so if one were to press on the liver, there are some other stimuli—alcohol, for example, can sometimes do it—that will cause a large amount of serotonin and the other hormones to be released all at once. And it can cause very severe cardiovascular manifestations.
Shubham Pant, MD: You’re saying like manifested in the heart? Like blood pressure manifestations?
Michael A. Morse, MD: Yes, that’s right. So, carcinoid crisis is often a scenario where people have very high blood pressures and then they’ll have sudden plummeting of their blood pressure. Some people with get severely bronchospastic and hypoxic—that means low oxygen—during that. But it happens so rapidly, because of the large amount of hormones released all at once, that it can be medically very difficult to intervene.
Shubham Pant, MD: So, Larry, what about in your case? I’m hoping you never had the carcinoma crisis.
Larry Pleasant: No, certainly not that I’ve been aware of. I’ve had, as I said, serious flushing episodes, but never anything that affected my blood pressure or heart rate or anything that I can equate to a carcinoid crisis.