What Are Neuroendocrine Tumours

Overview

Neuroendocrine tumours (NETs) are a collection of rare cancers that originate from neuroendocrine cells. Our body has a neuroendocrine system to tightly regulate its functions including metabolism, digestion, developmental growth, reproduction, energy balance, and response to stress. These functions are controlled by specialised neuroendocrine cells. Neuroendocrine cells are a type of cell that release hormones in response to nerve signals.¹

Neuroendocrine cells can be compared to airport officials controlling the crowd by directing everyone on time to different gates to board different flights. Your endocrine cells watch for nervous system impulses just like them. Your cells inform your endocrine system to release hormones when they receive the signal and inform your body of when and what to do. These cells have characteristics of both nerve cells and hormone-producing endocrine cells. They can be present in all of the body's organs and are involved in various bodily processes.²

Neuroendocrine cells do more than only monitor signals and initiate the release of hormones. Additionally, they produce and release hormones that regulate activity in the organ in which they are found. For example, pancreatic  islet cells (neuroendocrine cells), produce hormones such as insulin and glucagon to regulate glucose metabolism in our body.²

Endocrine cells become neuroendocrine tumours when they start to divide and multiply uncontrollably. These tumours can harm the organs where the cells are located.

Neuroendocrine tumours can be classified based on the location:^1,3

• Gastrinoma: A type of NET that occurs in the pancreas and produces excessive amounts of the hormone gastrin, leading to high levels of stomach acid
• Insulinoma: A type of NET that occurs in the pancreas and produces excessive amounts of insulin, leading to low blood sugar levels
• Carcinoid tumours: A type of NET that occurs in the gut, especially in the appendix (4%), small intestine (19%), large intestine (20%) and lungs (30%)
• Pheochromocytoma: A type of NET that occurs in the adrenal glands and produces hormones such as adrenaline or noradrenaline, leading to high blood pressure and heart problems
• Medullary thyroid cancer (MTC): Rarest type of NET that occurs in the thyroid gland
• Merkel cell carcinoma: A rare form of NET that appears in the merkel cells on the epidermis (top layer of skin). The head, neck, and arms are among the body parts where this form of NET frequently first appears
• Paraganglioma: Another extremely rare NET that arises outside the adrenal gland. They are frequently referred to as extra-adrenal paragangliomas since they can form in the belly or along nerve pathways in the brain, neck, chest, pelvis, or bladder

Neuroendocrine tumours can be also categorised by the appearance of the tumour cells under a microscope, and the rate at which the cells divide and spread throughout the body. NETs are graded into three stages, Grade 1 (slow-growing tumour), Grade 2 (steady-growing tumours) and Grade 3 (rapid-growing tumour). NETs may also be classified as "functional" or "non-functional”.Functional NETs (10-30%) are tumours that produce or release hormones and other symptom-causing chemicals. Non-functional NETs (60%) are tumours that do not produce hormones or not enough is released to produce symptoms.^3,4

Since most neuroendocrine tumours are non-functional in nature, they get diagnosed when the cancer becomes advanced i.e. the cancer cells spread (metastasis) to nearby organs, lymph nodes or bones causing the development of new symptoms.¹

Causes of neuroendocrine tumours

There is not one specific cause of neuroendocrine tumours. Still, scientists believe several genetic, hereditary, age, gender and other risk factors play an interconnected role in the development of these tumours.¹

Some of the causes and inherited genetic factors leading to neuroendocrine tumours are:^1,3,4

• Multiple endocrine neoplasia type 1 (MEN1): MEN1 is a genetic disorder (hereditary) linked to endocrine (hormone-producing gland) cancers. MEN1 was formerly referred to as Wermer syndrome. This condition causes your thyroid, parathyroid or adrenal glands to produce excess hormones and form tumours. In some cases, the tumours are formed in parts of the digestive tract (intestines) or kidneys
• Multiple endocrine neoplasia type 2 (MEN2): MEN 2 is a hereditary condition that causes your pancreas, pituitary or parathyroid to produce excess hormones and form tumours. RET is the name of the gene connected to MEN2. Medullary thyroid carcinoma and other malignancies linked to MEN2 are more likely to develop in people with RET gene mutations
• Neurofibromatosis type 1: This is a rare hereditary genetic condition where tumours grow on your skin and nerves, affecting your eyes and other parts of your body due to the mutation (alteration of the gene) on the NF1 gene. The prominent symptom of this condition is café-au-lait spots i.e. coffee and milk-coloured brown spots on the skin. NETs like carcinoid tumours and pheochromocytomas are more common in people with NF1
• Tuberous sclerosis complex: Tuberous sclerosis complex is a rare genetic disorder that affects many different parts of the body, including the brain, heart, skin, and kidneys. Spontaneous mutations in TSC1 and TSC2 genes cause TSC. People with tuberous sclerosis complex are at increased risk of developing neuroendocrine tumours in the pancreas and digestive system, as well as tumours in other parts of the body
• Von Hippel-Lindau syndrome (VHL): VHL is a genetically inherited condition which causes tumours to develop in multiple organs, including the brain, spinal cord, adrenal glands, and pancreas. People with VHL are at an increased risk of developing neuroendocrine tumours in adrenal glands (pheochromocytoma)

Studies showed NETs can occur at any age but it is more prevalent in the older population (the 40s-60s). It was also found NETs were more common in women than men as it was found 2% of NETs in women were found in the reproductive tract. People with conditions such as Chronic atrophic gastritis, Pernicious anaemia and Zollinger-Ellison syndrome were found to be more prone to developing NETs in the digestive system as it alters the amount of stomach acid produced.

If you have a family history of one of these illnesses is recommended to visit your GP to get genetic testing done. They might perform a tumour check along with genetic testing, so you can receive treatment earlier before it becomes a concern.

Signs and symptoms of neuroendocrine tumours

Depending on where the tumours are located, neuroendocrine tumour symptoms can differ. The neuroendocrine carcinoma of the gastrointestinal tract (GI NETs) and the neuroendocrine carcinoma of the lung consists of symptoms known as carcinoid syndrome.¹

When NETs release more hormones than your body requires, it results in carcinoid syndrome. Only 10% of those who have NETs go on to develop carcinoid syndrome. The most prevalent and initial symptom of carcinoid syndrome is uncomfortable flushing of the head and neck.^1,3,1,3

Some frequently prevalent signs and symptoms of neuroendocrine tumours are:^1,3,5,6

• Abdominal pain or discomfort: Some neuroendocrine tumours can cause abdominal pain or discomfort, especially if they are located in the digestive system
• Diarrhoea: Neuroendocrine tumours in the digestive system can cause diarrhoea, which may be watery or contain mucus or blood
• Weight loss: People with neuroendocrine tumours may experience weight loss due to decreased appetite or malabsorption of nutrients
• Fatigue

Symptoms associated with the size and/or location of the tumour:⁶

• Persistent pain at a particular location
• Any area of the body that has thickened or developed a lump
• Nausea 
• Persistent  hoarseness or a persistent cough
• Alterations in bowel or bladder patterns
• Jaundice
• Unexpected bleeding or discharge

If there are changes in the levels of your hormones you might experience ulcers, an increase or decrease in blood glucose levels, rashes, anxiety and confusion. It is important to know the mentioned symptoms can be related to other diseases and if you experience any of these symptoms visit your GP to get the right diagnosis and treatment. 

Management and treatment for neuroendocrine tumours

Based on the symptoms and diagnosis by checking hormone levels in the blood, imaging tests to locate tumours and biopsy your doctor will create a treatment plan suitable for you. In addition, the management and treatment of neuroendocrine tumours will also depend on the size, location, and grade of the tumour, as well as the patient's overall health. 

Some of the treatments for neuroendocrine tumours include:^5,6,7

• Surgery: Surgery is often the first line of treatment for neuroendocrine tumours, especially if the tumour is small and localised. The goal of surgery is to remove the entire tumour (complete surgical resection) and any surrounding tissue that might contain cancer cells
• Radiation therapy: Radiation therapy uses high-energy X-rays to destroy cancer cells. It may be used after surgery to help reduce the risk of the tumour returning, or it may be used to shrink the tumour before surgery
• Chemotherapy: Chemotherapy uses drugs to destroy cancer cells. It may be used alone or in combination with other treatments, depending on the type and location of the tumour
• Targeted therapy: Targeted therapy is a type of treatment that targets specific genetic changes in cancer cells. It may be used in conjunction with chemotherapy to improve the effectiveness of the treatment
• Hormone therapy: Hormone therapy is a treatment that blocks the production or action of hormones that can help the tumour grow. It may be used for neuroendocrine tumours that produce hormones or for tumours that are sensitive to hormones
• Symptom management: In addition to these treatments, patients with neuroendocrine tumours may also receive medications to manage symptoms, such as diarrhoea, abdominal pain, and flushing

It is important to note that the most appropriate treatment will depend on the individual patient and the specific features of their tumour, and a doctor should be consulted for personalised treatment regimens and to learn more about the possible side effects of the treatments.

FAQs

How are neuroendocrine tumours diagnosed?

Diagnosis of neuroendocrine tumours may include a physical examination, blood tests, imaging studies, and biopsy to check if the tumour is cancerous.⁷

How can I prevent neuroendocrine tumours?

The exact cause of neuroendocrine tumours is not known, so it is difficult to prevent them. Maintaining a healthy lifestyle, avoiding exposure to certain chemicals, and early detection and treatment of any genetic conditions may reduce the risk.¹

How common are neuroendocrine tumours

Neuroendocrine tumours are relatively rare, affecting 4000 people in the UK every year.

Who are at risk of neuroendocrine tumours

People with a family history of neuroendocrine tumours and certain genetic conditions may be at increased risk.¹

What are the different types of neuroendocrine tumours

The different types of neuroendocrine tumours include gastrinoma, insulinoma, carcinoid tumours, and pheochromocytoma, among others.^1,3

When should I see a doctor?

You should see a doctor if you have any symptoms that suggest you may have a neuroendocrine tumour, such as abdominal pain, diarrhoea, flushing, usual bleeding, or unexplained weight loss.⁶

Summary

Neuroendocrine tumours are a type of cancer that arises from specialised cells that release hormones in response to nerve signals. They can occur anywhere in the body and can produce excessive amounts of hormones. Factors that increase the risk of neuroendocrine tumours include family history, inherited genetic conditions, and other diseases that increase stomach acid.

If you have symptoms such as abdominal cramping, flushing, or unexplained weight loss, it is important to see your GP for an evaluation so an appropriate diagnosis can be made. Based on the diagnosis, your doctor will talk about the management, and treatment of neuroendocrine tumours which may include various tests and treatments, such as surgery, radiation therapy, and chemotherapy. If you have a history of neuroendocrine tumours in your family, get in touch with support programs and opt for early detection through genetic testing.