The Sounds of a Zebra – Symptoms of Neuroendocrine Cancer

Today is Neuroendocrine Cancer Awareness Day. This annual event, coordinated by the International Neuroendocrine Cancer Alliance, aims to raise awareness about this rare but growing cancer. As a company that was, in essence, founded to create a better understanding of neuroendocrine tumor activity and treatment response, we join the NET community in trying to raise awareness about this often misdiagnosed disease. Following is a summary of the symptoms of this disease and some resources to get help should you suspect that you or a loved one is dealing with neuroendocrine cancer.

NETs, or neuroendocrine tumors, are uncontrolled dividing cells originating from endocrine and neural tissue. This means a NET can form in a variety of organs of the body. The ubiquity and variety of neuroendocrine cells are the main reasons patients presenting with NET symptoms are often incorrectly diagnosed for prolonged periods of time. This misdiagnosis can delay NET findings and treatment – sometimes for years.

Research indicates NET patients, on average, visit six different healthcare providers over the course of fifty-four months before a correct NET diagnosis. By the time a diagnosis of NET is made, 58% of patients already have metastases (the NET cells have also moved to another area of the body).¹

Needless delays in diagnosis and the potential to catch NETs prior to metastases are critical reasons to create awareness of Neuroendocrine Cancer with NET November. Step one to quicker, better outcomes for NET patients is understanding the symptoms of NETs. Education and knowledge are powerful tools in earlier diagnosis and more treatable disease. Although the diversity of NETs is significant, below, we list more common symptoms across diagnoses and specific NET types.

Please see a healthcare provider if you are experiencing any combination of the symptoms below.

Common Symptoms of Neuroendocrine Tumors²

• Hypoglycemia – low blood sugar
• Hyperglycemia – high blood sugar
• Anxiety or confusion
• Frequent urination

Carcinoid Syndrome – refers to a group of symptoms caused by a NET releasing large amounts of hormone-associated molecules. It is an urgent condition that requires immediate attention by a healthcare provider. Carcinoid syndrome may happen in people with any type of NET. The signs of carcinoid syndrome include³:

• Persistent Flushing (warmth, redness in the face that lasts more than a few minutes)
• Fast or irregular heartbeat
• Wheezing and difficulty breathing
• Pellagra (inflamed skin, diarrhea, sores in mouth)
• Abdominal cramps
• Severe Diarrhea

Neuroendocrine tumors will have symptoms based on their anatomical location and physiological purpose. The following are symptoms associated with specific types of NETs:

Gastroenteropancreatic Neuroendocrine Tumors (GEP-NETs) – these can develop in any part of the gastrointestinal tract (intestines, pancreas, stomach, etc.). The most common sites of GEP-NETs are the appendix and the ileum. GEP-NETs have been steadily increasing in the United States since the 1980s. Signs or symptoms of GEP-NETs may include:⁴

• Flushing – warmth, redness in the face
• Periodic abdominal pain
• Wheezing
• Diarrhea
• Persistent fatigue
• Constipation
• Unexplained weight loss
• History of Multiple Endocrine Neoplasia (MEN 1 or 2)

Bronchopulmonary Neuroendocrine Tumors (BP-NETs or NETs of the lungs) – also called Lung NETs, these represent about 25% of all neuroendocrine cancers. These usually develop in the airways (bronchi). Signs or symptoms of BP-NETs may include⁵:

• Persistent cough
• Hemoptysis (coughing up blood)
• Wheezing
• Dyspnea (shortness of breath)
• Chest pain (specifically with the act of breathing)
• Chronic fatigue
• frequent pneumonia

Pancreatic Neuroendocrine Tumors (Pan-NETs) – signs or symptoms depend mainly on the type of hormone the tumor releases. For example, tumors releasing gastrin, a hormone that stimulates acid production in the stomach, have acid reflux and burning abdominal pain as primary symptoms. Other hormone-secreting NETs differ in their primary signs. Below, we have broken them out by the type of hormone the NET is overproducing, which gives a ‘cluster’ of symptoms^6,7

• • Hyperglycemia (high blood sugar)
  • Severe swelling or irritation of the skin
  • Mouth sores
  • Anemia (low blood levels)
  • Unexplained weight loss

VIPoma (Vaso Intestinal Peptide Releasing Tumor)

• • Severe, watery diarrhea
  • Muscle weakness
  • Fatigue
  • nausea

Understanding the signs and symptoms of neuroendocrine cancer is the first step in helping to recognize and then begin treatment for these rare and varied forms of cancer. Many in the constellation of symptoms presented by a NET are somewhat common, but, as the saying goes, sometimes those hoofbeats are actually Zebras. Knowing NET is an issue as soon as possible provides more treatment options and improved potential outcomes.

If you, or someone you know, has been experiencing any of the symptoms referenced above, see your healthcare provider and discuss your concerns about neuroendocrine cancer and options for diagnosis or monitoring. Learn more at any of these resources:

• NET Research Foundation
• International Neuroendocrine Cancer Alliance
• The Carcinoid Cancer Foundation
• North American Neuroendocrine Tumor Society

NOTES:

Hyperglycemia can be a life-threatening situation. Seek immediate medical attention if it is experienced.

¹Patient-reported Burdon of a Neuroendocrine Tumor (NET) Diagnosis: Results From the First Global Survey of Patients with NETs: Journal of Global Oncology. 2017 Feb; 3(1): 43-53.

²Neuroendocrine Tumor Symptoms: MD Anderson Cancer Center.

³Pandit S, Annamaraju P, Bhusal K. Carcinoid Syndrome. [Updated 2023 Feb 13]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2023 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK448096

⁴Gastrointestinal Neuroendocrine Tumors: Penn Medicine Abramson Cancer Center

⁵Neuroendocrine Tumors of the Lung:  Current Challenges and Advances in the Diagnosis and Management of Well-Differentiated Disease. Journal of Thoracic Oncology. Vol 12, Issue 3. March, 2017.

⁶Pancreatic Neuroendocrine Tumors – Patient Information: Hartford HealthCare.

⁷Pancreatic Neuroendocrine Tumor: Cedars-Sinai