The most common initial symptoms of neuroendocrine cancer among patients include anxiety, gastritis, inflammatory bowel disease, irritable bowel syndrome, menopause, and asthma, however, the symptoms may vary based on the site and stage of cancer.
A doctor can mistakenly detected or suspected Neuroendocrine tumors due to the presence of other clinical symptoms. If NETs cause clinical symptoms due to the hormones secreted, they are “functional”. However, most NETs do not produce biologically active hormones and doctors consider them as “non-functional”. Both functional and non-functional NETs appear late, and non-specific symptoms are often attributed to alternative diagnoses. In fact, in an International survey of NET-confirmed patients, the most common initial symptoms were anxiety, gastritis, inflammatory bowel disease, irritable bowel syndrome, menopause, and asthma.
While certain symptoms may indicate the diagnosis and location of NET; NET of the small intestine can cause extensive fibrosis, which is recurrent abdominal pain due to secondary small bowel obstruction or mesenteric ischemia. A retrospective study consisting of 121 patients with mid-intestinal NET who underwent surgery, significant mesenteric fibrosis and intestinal ischemia were observed in 65% and 38% of patients. In fact, the bronchopulmonary reticulum is a centrally located lesion that can cause bronchial obstruction, cough, recurrent obstructive pneumonia, and hemoptysis. In addition, bronchopulmonary NETs may be a source of ectopic adrenocorticotropic hormone (ACTH) production. Therefore, clinicians should consider this diagnosis in unexplained Cushing syndrome1.
The carcinoid syndrome, characterized by flushing, diarrhoea and valvular heart disease, occurs when hormones produced by NETs enter the systemic circulation. It bypasses hepatic metabolism, which can deactivate hormones, usually following liver metastases. In a retrospective cohort study, carcinoid syndrome was reported in 6 to 13% of patients with pathologically confirmed gastrointestinal NETs and less than 1% of patients with bronchopulmonary NETs. Tumors of the spine (distal colon and rectum) are usually hormonally silent and do not cause carcinoid syndrome.
Abdominal pain has been reported in approximately 40% of patients and may be associated with mesenteric fibrosis. Wheezing or bronchospasm occurs in 10-20% of patients and is due to the overproduction of hormones. The release of histamine can cause itching and rashes on the skin. Palpitations are commonly observed due to hormone overproduction and are often reported to occur spontaneously or after a stressful episode. The heartbeat can be short-term or long, up to 30 minutes. There have been minor reports of malnutrition due to malnutrition associated with uncontrolled diarrhoea. People with carcinoid syndrome have a poorer quality of life than patients with NEN without carcinoid syndrome. Not all diarrhoea in people with carcinoid syndrome is hormonal1.
Gastroenteropancreatic neuroendocrine tumors
GEP-NET is characterized by its ability to produce, store, and release many peptide hormones and biogenic amines, which can cause a variety of clinical syndromes.
The various signs and symptoms of GEP-NETs based on their site of origin and hormonal activity are:
- Functional carcinoid: Carcinoid syndrome (diarrhoea, flushing and heart disease)
- Gastrinoma: Zollinger Ellison syndrome (duodenal ulceration, diarrhoea, acid hypersecretion, esophagitis)
- Insulinoma: Hypoglycemia
- Glucagonoma: Diabetes and erythema
- VIPoma: WDHA syndrome or Verner-Morrison syndrome (watery diarrhoea, hypokalemiaachlorhydria)2
Symptoms of Lung carcinoid tumors
About 25% or more of people with lung carcinoid tumors have no symptoms. Doctors often detect this type of tumor by diagnostic tests for other diseases, such as a chest X-ray infection.
If there are symptoms, it is usually a cough or wheezing. Coughing can cause blood to build up in the mucus or phlegm. If the tumor is large enough to block the airway, an infection called obstructive pneumonia can develop.
Symptoms of Pancreatic carcinoid tumors
Neuroendocrine tumors of the pancreas sometimes do not cause symptoms. However, some of the symptoms often observed among patients with pancreatic carcinoid tumors include Stomach ulcers, Diabetes, Indigestion, Diarrhoea, Pain in your abdomen or back, Weight loss, Low blood sugar, Constipation, Fatigue, Heartburn, Muscle cramps, Yellowing of the eyes or skin, Skin rash, and Weakness3.
- 1.Carcinoid Tumors of the Lungs. Cleveland Clinic logo. Published 2021. Accessed March 2022. https://my.clevelandclinic.org/health/diseases/14783-carcinoid-tumors-of-the-lungs
- 2.Díez M, Teulé A, Salazar R. Gastroenteropancreatic neuroendocrine tumors: diagnosis and treatment. Ann Gastroenterol. 2013;26(1):29-36. https://www.ncbi.nlm.nih.gov/pubmed/24714698
- 3.Pancreatic neuroendocrine tumors. Mayo Clinic. Published 2021. Accessed March 2022. https://www.mayoclinic.org/diseases-conditions/pancreatic-neuroendocrine-tumors/symptoms-causes/syc-20352489