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Neuroendocrine%20tumors Signs and Symptoms
Definition
- Rare, small, slow-growing epithelial neoplasms with predominant neuroendocrine differentiation found in most organs of the body
Pathophysiology
- Arise from cells throughout the diffuse endocrine system
- Carcinoid tumors and pancreatic neuroendocrine tumors (NETs) are the most common
- Carcinoid tumors arise from the lungs and bronchi, stomach, small intestine, appendix, rectum or thymus
- Pancreatic NETs arise from the pancreas
- Most common subtypes are:
- Insulinomas that produce insulin
- Gastrinomas which produce gastrin, a hormone that helps digest food
- Glucagonomas that produce glucagon, a hormone that helps to raise blood sugar levels
- VIPomas produce vasoactive intestinal peptide (VIP) that helps digestion and a number of other body processes
- Somatostatinomas produce somatostatin that helps with digestion
- Most common subtypes are:
- Others less common NETs arise in the parathyroid glands, adrenal glands, pituitary gland, and calcitonin-producing cells of the thyroid gland
- Majority of the NETs are sporadic but some tumors are caused by inherited genetic syndrome such as multiple endocrine neoplasia (MEN), Von-Hippel Lindau (VHL) disease, tuberous sclerosis complex, and neurofibromatosis
- They have the ability to store and secrete various peptides and neuroamines
- Some of these substances can cause specific clinical syndromes while other substances may produce elevated plasma or urine levels that are not associated with a specific symptom complex or syndrome
Clinical Manifestation
- Flushing
- Usually the dry type
- Secondary to prostaglandins, kinins, and serotonin
- Characteristic depends on the location of the tumor
- Diarrhea
- Commonly the secretory type
- Produces large-volume stools
- Persists with fasting
- Relieved by proton pump inhibitor
- Abdominal pain
- Usually severe, persistent, and disturbs sleep
- Dyspepsia
- Ulcer
- Relieved by proton pump inhibitor use that is very suggestive of gastrinoma diagnosis
- Steatorrhea
- Bronchoconstriction
- Wheezing due to bronchospasm is seen in 1/3 of patients with carcinoid syndrome that is usually caused by substance P, histamine, or serotonin
- Hypoglycemia
- Seen in patients with insulinoma as part of Whipple triad (hypoglycemic symptoms, blood glucose level of <40 mg/dL, and relief of symptoms with glucose)
- Hyperglycemia
- Dementia
- Dermatoses (eg urticaria, pellagra, cafe au lait)
- Obstructive symptoms (eg nausea, vomiting, cholestasis)
- Weight loss
Functional NETs
- Symptoms are due to excess hormone production
- Most common functionally active NETs include carcinoids, insulinomas, gastrinomas, VIPoma and glucagonomas
- Most common manifestation is carcinoid syndrome caused by elevated levels of serotonin and is associated with carcinoid tumors from the small intestine or appendix
- Symptoms of carcinoid syndrome:
- Vasomotor symptoms (eg facial flushing, telangiectasia, chronic facial cyanosis, rhinitis)
- Increased intestinal motility (eg diarrhea, borborygmi, abdominal pain)
- Heart failure (eg endocardial fibrosis, pulmonary stenosis, tricuspid insufficiency)
- Bronchoconstriction (eg asthma)
- Symptoms of carcinoid syndrome:
- Most nonfunctional tumors are asymptomatic and not associated with clinical hormonal syndrome
- Symptoms such as abdominal discomfort, diarrhea, bowel obstruction, weight loss, and jaundice are due to local growth and metastasis
- They may not be diagnosed until they have progressed to advanced disease because they are slow-growing tumors
- They are often found incidentally during imaging studies or surgery and their neuroendocrine origin may be noted only after histologic examination
- They are still biologically active even though they do not secrete peptides which cause a clinical syndrome
- The peptides that they secrete are used for their diagnosis [eg chromogranins, especially chromogranin A (CgA), and pancreatic polypeptide]
- The presence of pancreatic mass without hormonal symptoms in a patient who has increased serum pancreatic polypeptide or CgA level is suggestive of non-functional NETs
- The peptides that they secrete are used for their diagnosis [eg chromogranins, especially chromogranin A (CgA), and pancreatic polypeptide]
