10 Warning Signs and Symptoms of Neuroendocrine Tumors You Should Know

Neuroendocrine tumors (NETs) are rare cancers that develop in cells of the neuroendocrine system, which consists of cells that receive signals from the nervous system and respond by producing hormones. These tumors can occur anywhere in the body but are most commonly found in the lungs, pancreas, and gastrointestinal tract. Because neuroendocrine tumors can produce excess hormones, they often cause a variety of symptoms that may seem unrelated at first.

Understanding the symptoms of neuroendocrine cancer is crucial for early detection and treatment. While these tumors are relatively rare, affecting approximately 5 to 7 people per 100,000 annually, their symptoms can be subtle and easily mistaken for other conditions. This article will guide you through the 10 most common warning signs and symptoms of neuroendocrine tumors to help you recognize when medical attention is needed.

1. Persistent Abdominal Pain and Cramping

One of the most frequently reported symptoms of neuroendocrine tumors, particularly those in the gastrointestinal tract or pancreas, is chronic abdominal pain. This discomfort can manifest as:

• Dull, aching pain in the middle or upper abdomen
• Intermittent cramping that comes and goes
• Pain that worsens after eating
• Discomfort that persists for weeks or months

The pain occurs because the tumor may be physically blocking the intestine or pancreatic ducts, or because it’s producing hormones that affect digestion and intestinal motility. Unlike typical stomach upset, this pain tends to be persistent and doesn’t respond well to over-the-counter medications. If you experience unexplained abdominal pain lasting more than two weeks, especially when accompanied by other symptoms on this list, it’s important to consult a healthcare provider.

2. Chronic Diarrhea

Diarrhea is a hallmark symptom of certain types of neuroendocrine tumors, especially those that produce excessive amounts of hormones like serotonin, vasoactive intestinal peptide (VIP), or gastrin. This isn’t your typical bout of diarrhea from food poisoning or a stomach virus.

Characteristics of NET-related diarrhea include:

• Watery stools occurring multiple times per day (often 5-10+ times)
• Persistent symptoms lasting weeks or months
• Diarrhea that doesn’t respond to typical antidiarrheal medications
• Episodes that may worsen after eating certain foods, particularly high-fat meals
• Nighttime diarrhea that disrupts sleep

The excess hormones produced by these tumors can stimulate the intestines to secrete more fluid and increase intestinal motility, leading to frequent, watery bowel movements. This chronic diarrhea can lead to dehydration, electrolyte imbalances, and significant impact on quality of life.

3. Facial Flushing

Flushing is one of the most characteristic symptoms of carcinoid syndrome, which occurs when certain neuroendocrine tumors release large amounts of hormones into the bloodstream. This symptom presents as:

• Sudden redness and warmth spreading across the face and neck
• Episodes lasting from a few minutes to several hours
• Skin that may feel hot to the touch during episodes
• Possible spread to the upper chest and back
• Accompanying feelings of warmth or heat

The flushing is typically triggered by stress, alcohol consumption, certain foods (like aged cheeses or cured meats), or exercise. Unlike normal blushing, these episodes are often more intense, last longer, and occur without obvious emotional triggers. Some patients also experience visible red or purple patches on the skin during these episodes. The flushing occurs because hormones like serotonin and histamine cause blood vessels near the skin’s surface to dilate.

4. Wheezing and Difficulty Breathing

Respiratory symptoms can occur in neuroendocrine tumors, particularly lung carcinoid tumors or when carcinoid syndrome affects the respiratory system. These symptoms include:

• Wheezing similar to asthma
• Shortness of breath during normal activities
• Persistent cough that doesn’t resolve
• Chest tightness or pressure
• Difficulty taking deep breaths

When neuroendocrine tumors develop in the lungs, they can physically obstruct airways, causing breathing difficulties. Additionally, the excess hormones produced by some NETs can cause bronchospasm—a tightening of the muscles around the airways—similar to what occurs in asthma. These respiratory symptoms may be mistaken for asthma, chronic obstructive pulmonary disease (COPD), or recurring respiratory infections, which can delay proper diagnosis. If you have persistent respiratory symptoms that don’t respond to typical asthma treatments, especially when combined with other symptoms like flushing or diarrhea, further investigation may be warranted.

5. Unexplained Weight Loss

Significant, unintentional weight loss is a common symptom of many cancers, including neuroendocrine tumors. This weight loss typically:

• Occurs without changes to diet or exercise habits
• Amounts to 5% or more of body weight over 6-12 months
• Happens despite maintaining normal or increased appetite
• May be accompanied by muscle wasting and weakness

Several mechanisms contribute to weight loss in NET patients. The tumor itself consumes nutrients and energy, while chronic diarrhea prevents proper absorption of nutrients from food. Some NETs produce hormones that increase metabolism, causing the body to burn calories more rapidly. Additionally, the general feeling of illness and reduced appetite that can accompany cancer contributes to decreased food intake. Weight loss combined with other symptoms like diarrhea, flushing, or abdominal pain should prompt immediate medical evaluation.

6. Heart Palpitations and Rapid Heartbeat

Cardiovascular symptoms are another manifestation of hormone-secreting neuroendocrine tumors. Patients may experience:

• Sudden awareness of heartbeat (palpitations)
• Racing heart rate (tachycardia) even at rest
• Irregular heartbeat or skipped beats
• Sensation of heart pounding in the chest, neck, or throat
• Feeling lightheaded or dizzy during episodes

These symptoms occur because hormones like serotonin, norepinephrine, and other vasoactive substances released by NETs can directly affect heart function and blood vessel tone. The hormones can cause blood vessels to constrict or dilate suddenly, leading to changes in blood pressure and heart rate. Over time, chronic exposure to these hormones can even cause damage to heart valves, a condition called carcinoid heart disease. If you experience new or worsening heart palpitations, especially in combination with flushing or breathing difficulties, seek medical attention promptly.

7. Stomach Ulcers and Severe Heartburn

Some neuroendocrine tumors, particularly gastrinomas (a type of pancreatic NET), produce excessive amounts of gastrin, a hormone that stimulates stomach acid production. This leads to:

• Severe, persistent heartburn or acid reflux
• Burning pain in the upper abdomen
• Multiple stomach or duodenal ulcers
• Ulcers that recur despite treatment
• Ulcers in unusual locations
• Nausea and vomiting

This constellation of symptoms is known as Zollinger-Ellison syndrome when caused by a gastrinoma. The excess acid production can cause severe damage to the stomach and intestinal lining, leading to painful ulcers that are difficult to heal. Unlike typical peptic ulcers caused by H. pylori bacteria or NSAID use, these ulcers are caused by excessive acid production driven by tumor-secreted hormones. Patients often report that their symptoms don’t fully respond to standard acid-reducing medications, or that ulcers keep returning after treatment.

8. Low Blood Sugar Episodes (Hypoglycemia)

Insulinomas, a type of pancreatic neuroendocrine tumor, produce excessive insulin, leading to dangerous drops in blood sugar levels. Symptoms of hypoglycemia include:

• Confusion, difficulty concentrating, or mental fog
• Sweating, shakiness, and trembling
• Extreme hunger
• Rapid heartbeat and anxiety
• Dizziness, lightheadedness, or fainting
• Blurred vision
• Weakness and fatigue
• Irritability or mood changes

These episodes typically occur during fasting states, such as between meals, during the night, or first thing in the morning before eating. The symptoms quickly improve after eating or drinking something containing sugar. What distinguishes insulinoma-related hypoglycemia from other causes is the pattern of recurrent episodes, especially those occurring after fasting or exercise, and blood sugar levels that drop below 50 mg/dL during symptomatic episodes. Severe hypoglycemia can be dangerous and may lead to seizures or loss of consciousness if not treated promptly.

9. Skin Rash and Changes

Certain neuroendocrine tumors can cause distinctive skin manifestations. The most notable is necrolytic migratory erythema, associated with glucagonomas (pancreatic NETs that produce excess glucagon). Skin symptoms include:

• Red, blistering rash that spreads across the body
• Rash particularly affecting the face, groin, buttocks, and legs
• Painful or itchy patches
• Skin lesions that may crust over and heal with pigmentation changes
• Scaling and thickening of the skin
• Angular cheilitis (inflammation at the corners of the mouth)
• Glossitis (inflamed, smooth tongue)

The rash associated with glucagonomas is cyclical—it appears, worsens, then partially heals, only to recur in the same or different areas. This pattern, combined with other symptoms like diabetes or weight loss, can be a key diagnostic clue. The skin changes occur due to the metabolic effects of excess glucagon and associated nutritional deficiencies, particularly amino acid and zinc deficiencies.

10. Fatigue and Weakness

Persistent, overwhelming fatigue is a common but often overlooked symptom of neuroendocrine tumors. This fatigue differs from normal tiredness in several ways:

• Not relieved by adequate rest or sleep
• Disproportionate to activity level
• Interferes with daily activities and work
• Accompanied by muscle weakness
• Feeling of complete exhaustion even after minimal exertion
• Mental fatigue and difficulty concentrating

Multiple factors contribute to fatigue in NET patients. The tumor itself and the body’s immune response to it consume energy. Chronic diarrhea leads to nutritional deficiencies and dehydration. Hormonal imbalances caused by the tumor disrupt normal metabolism. Sleep may be disrupted by symptoms like nighttime diarrhea, flushing, or low blood sugar. Additionally, the psychological burden of dealing with chronic symptoms contributes to exhaustion. While fatigue alone is rarely diagnostic, when combined with other symptoms on this list, it strengthens the case for medical investigation.

Main Causes of Neuroendocrine Tumors

The exact causes of neuroendocrine tumors remain largely unknown, but research has identified several factors that may increase risk:

Genetic Factors

Several inherited genetic syndromes significantly increase the risk of developing neuroendocrine tumors:

• Multiple Endocrine Neoplasia Type 1 (MEN1): A genetic syndrome that causes tumors in multiple endocrine glands, including pancreatic NETs
• Multiple Endocrine Neoplasia Type 2 (MEN2): Associated with medullary thyroid carcinoma, a type of neuroendocrine cancer
• Von Hippel-Lindau (VHL) syndrome: Increases risk of pancreatic NETs among other tumor types
• Neurofibromatosis Type 1 (NF1): May increase risk of certain NETs, particularly pheochromocytomas
• Tuberous Sclerosis Complex: Associated with increased risk of pancreatic NETs

Sporadic Development

The vast majority of neuroendocrine tumors (over 90%) occur sporadically without any identifiable genetic syndrome or clear cause. These tumors appear to develop due to random genetic mutations that accumulate over time in neuroendocrine cells.

Age and Demographics

Certain demographic factors are associated with higher NET incidence:

• Age: Most commonly diagnosed in adults aged 50-70, though they can occur at any age
• Race: Slightly higher incidence in African Americans compared to Caucasians
• Gender: Some types are more common in women, others in men

Other Potential Risk Factors

While research is ongoing, some studies suggest possible associations with:

• Family history of neuroendocrine tumors, even without identified genetic syndromes
• Certain chronic conditions affecting the stomach (such as chronic atrophic gastritis)
• Immune system disorders

It’s important to note that having risk factors doesn’t mean someone will definitely develop a neuroendocrine tumor, and many people diagnosed with NETs have no identifiable risk factors.

Prevention Strategies

Because the causes of most neuroendocrine tumors are unknown and many occur sporadically, there are no guaranteed prevention methods. However, certain strategies may help with early detection and potentially reduce risk:

Genetic Counseling and Testing

For individuals with a family history of neuroendocrine tumors or known hereditary syndromes:

• Consider genetic counseling to assess your risk
• Undergo genetic testing if appropriate to identify hereditary syndromes
• If you have a genetic syndrome associated with NETs, follow recommended surveillance protocols
• Regular screening can detect tumors early when they’re most treatable

General Health Maintenance

While these measures haven’t been proven to prevent NETs specifically, they support overall health and may aid in early detection:

• Regular medical check-ups: Annual physical examinations can help detect unusual symptoms early
• Report persistent symptoms: Don’t ignore ongoing digestive issues, unexplained weight loss, or other concerning symptoms
• Maintain detailed family health history: Know your family’s cancer history and share it with your healthcare provider
• Healthy lifestyle: While not proven to prevent NETs, maintaining a balanced diet, regular exercise, avoiding tobacco, and limiting alcohol supports overall health

Awareness and Early Detection

The most effective “prevention” strategy for NETs is actually early detection:

• Be aware of the warning signs and symptoms listed in this article
• Seek medical attention for persistent, unexplained symptoms
• Don’t dismiss symptoms as “just stress” or “normal aging”
• If initial treatments for symptoms don’t work, advocate for further investigation
• For those at high genetic risk, adhere to recommended screening schedules

Early-stage neuroendocrine tumors are often more treatable and have better outcomes than those detected at later stages.

Frequently Asked Questions

What is the difference between a neuroendocrine tumor and neuroendocrine cancer?

The terms are often used interchangeably, but there’s a technical distinction. Neuroendocrine tumor (NET) is a broad term that includes both benign and malignant growths. Neuroendocrine cancer or neuroendocrine carcinoma typically refers to the malignant, more aggressive forms. NETs are classified by grade (how abnormal the cells look) and differentiation (how much they resemble normal cells), which helps determine their behavior and treatment approach.

Are neuroendocrine tumor symptoms constant or do they come and go?

Symptoms can vary significantly. Some symptoms like chronic diarrhea or abdominal pain may be persistent, while others like flushing, wheezing, or heart palpitations often occur in episodes that come and go. The intermittent nature of some symptoms can make diagnosis challenging, as patients may feel fine when they see their doctor. Keeping a symptom diary can be helpful for identifying patterns and triggers.

How long can you have a neuroendocrine tumor without knowing?

Many neuroendocrine tumors grow slowly and may not cause symptoms for years. Some are discovered incidentally during imaging or procedures for unrelated conditions. Non-functional NETs (those that don’t produce excess hormones) may not cause symptoms until they grow large enough to press on nearby organs. In some cases, people have had tumors for 5-10 years before diagnosis. This is why NETs are sometimes called “slow-growing” cancers.

Can neuroendocrine tumors cause anxiety and panic attacks?

Yes, certain neuroendocrine tumors, particularly pheochromocytomas and paragangliomas, can produce hormones like adrenaline and noradrenaline that cause symptoms identical to panic attacks: rapid heartbeat, sweating, trembling, feelings of impending doom, and high blood pressure. Additionally, the low blood sugar caused by insulinomas can trigger anxiety-like symptoms. If you experience panic attack symptoms along with other signs like flushing, high blood pressure, or headaches, mention this to your doctor.

What should I do if I have several of these symptoms?

If you’re experiencing multiple symptoms listed in this article, especially if they’re persistent or worsening, schedule an appointment with your primary care physician. Bring a list of all your symptoms, when they started, how often they occur, and anything that makes them better or worse. Your doctor may order blood tests, urine tests, or imaging studies. Be prepared to advocate for yourself if symptoms persist despite initial negative tests—diagnosing NETs can be challenging and may require specialized testing.

Are neuroendocrine tumors hereditary?

Most neuroendocrine tumors (over 90%) occur sporadically without a hereditary component. However, about 5-10% of NETs are associated with inherited genetic syndromes such as Multiple Endocrine Neoplasia (MEN1 or MEN2), Von Hippel-Lindau syndrome, or neurofibromatosis type 1. If you have a personal or family history of NETs or related syndromes, genetic counseling may be appropriate to assess your risk and determine if surveillance is recommended.

Do all neuroendocrine tumors cause carcinoid syndrome?

No, carcinoid syndrome (the collection of symptoms including flushing, diarrhea, wheezing, and heart issues) occurs in only about 10% of people with neuroendocrine tumors. It’s most common when the tumor has spread to the liver, which allows the hormones to bypass the liver’s filtering effect and enter general circulation. Tumors in certain locations, like the midgut (small intestine and appendix), are more likely to cause carcinoid syndrome than tumors in other locations.

Can stress or diet cause neuroendocrine tumors?

There is no evidence that stress or diet directly causes neuroendocrine tumors to develop. However, once you have a hormone-secreting NET, certain foods, beverages, and stress can trigger or worsen symptoms. Common triggers include alcohol, aged cheeses, cured meats, chocolate, and high-fat foods. These don’t cause the tumor itself but can provoke symptom episodes like flushing or diarrhea in people who already have functional NETs.

References:

• American Cancer Society – Gastrointestinal Carcinoid Tumors
• Cancer.Net – Neuroendocrine Tumors
• Mayo Clinic – Neuroendocrine Tumors
• NHS – Neuroendocrine Tumours
• National Cancer Institute – Gastrointestinal Carcinoid Tumors
• National Organization for Rare Disorders – Neuroendocrine Tumors