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Common gastrointestinal symptoms could indicate a neuroendocrine tumor

At least 13 types of neuroendocrine cells exist in the gastrointestinal (GI) tract, all of which secrete bioactive peptides or amines.2

Neuroendocrine tumors (NETs) can arise from these cells in the small intestine and proximal colon and exhibit secretory activity.3

NETs arising in the distal colon and rectum, conversely, are usually nonfunctional and cause symptoms owing to increasing tumor mass.2-4

All of these GI NETs can produce nonspecific symptoms that are uncomfortable for patients and challenging for physicians.3

The clues to carcinoid syndrome

Carcinoid syndrome is one of the more common clinical manifestation of NETs, occurring in 8% to 35% of patients.5

Carcinoid, or functional, syndrome occurs most frequently when certain types of gastrointestinal (GI) NETs metastasize to the liver, which allows secreted serotonin and other vasoactive substances to bypass hepatic metabolism and directly enter systemic circulation.2,5 Other substances include corticotropin, histamine, dopamine, substance P, neurotensin, prostaglandins, kallikrein, and tachykinins.4

Oversecretion of these substances can cause the cluster of symptoms known as carcinoid syndrome. These include flushing, diarrhea, cramping, and wheezing.6 Additionally, cardiac disease is one of the most serious aspects of carcinoid syndrome, occurring in approximately 2/3 of patients.7

Because these symptoms are nonspecific they are often attributed to other more common conditions, such as irritable bowel syndrome. However, by distinguishing certain clues, physicians can make a differential diagnosis to rule out or preliminarily identify a GI NET as a possible cause.3,8

Patients may be more likely to have cardiac disease when they exhibit 5-HIAA levels ≥300 µmol (57 mg) over 24 hours and flushing episodes ≥ 3 per day.8

Other types of GI NETs

GI NETs may be associated with other symptoms and syndromes, depending on the tumor’s site of origin. Click on the graphic to launch and learn more.

Stomach

NET incidence: 0.3 per 100,000 cases1

Predominant hormone: Gastrin10

Major syndromes/symptoms: Pain, vomiting, upper GI bleeding, dyspepsia, anemia, heme-positive stools, gastric polyps7

Median survival with distant metastases: 13 mos1

Duodenum/Jejunum, ileum

NET incidence: 0.19 per 100,000 cases1 / 0.67 per 100,000 cases1

Predominant hormone (other substances): Somatostatin, secretin, cholecystokinin, motilin, GIP10

Major syndromes/symptoms: Abdominal pain, small bowel obstruction4

Median survival with distant metastases: 57 mos/65 mos1

Appendix

NET incidence: 0.15 per 100,000 cases1

Predominant hormone (other substances): Serotonin, substance P7

Major syndromes/symptoms: Nonspecific symptoms, signs of acute appendicitis7

Median survival with distant metastases: 31 mos1

Colon

NET incidence: 0.20 per 100,000 cases1

Predominant hormone (other substances): Somatostatin, peptide YY, neurotensin10

Major syndromes/symptoms: Pain, anorexia, weight loss4

Median survival with distant metastases: 7 mos1

Rectum

NET incidence: 0.86 per 100,000 cases1

Predominant hormone involvement (other substances): Glucagon, PP, glicentin-like peptides4

Major syndromes/symptoms: Rectal bleeding, pain, constipation4

Median survival with distant metastases: 26 mos1

Chart showing the Classification of Neuroendocrine Tumors (NETs)