Carcinoid Tumor/Syndrome
  • Most common gastrointestinal endocrine tumor (75% of such neoplasms)
  • Presenting symptoms:
    • Gastrointestinal bleeding
    • Abdominal pain
    • GI obstruction due to:
      • tumor growth
      • tumor-induced mesenteric fibrosis
    • Symptoms associated with hormones secreted by the tumor
  • Carcinoid refers to tumor slow growth (4-5 years between onset of symptoms and diagnosis) and initial underestimation of malignant potentialand.
  • Tumor properties:
    • Arise from neuroendocrine cells {neuroendocrine cells are most common in: the gastrointestinal tract, pulmonary bronchi, pancreas}
    • Tumors are most commonly found in the appendix, ileum, and rectum (may be found anywhere from the stomach to the rectum)
    • In the small intestine: carcinoid tumors -- one of the two most common malignancies.
    • 90% of carcinoid tumors derived from enterochromaffin (Kulchitsky cells) within the gastrointestinal tract
    • From a small, primary tumor, peritoneal and mesenteric spread induces by fibrotic reactions (causing obstruction, vascular compromise, intestinal kinking)
  • Gastric carcinoid tumor may arise from:
    • enterochromaffin cells or
    • histamine-secreting enterochromaffin-like cells
      • increased risk factors for this etiology:
        1. chronic atrophic gastritis
          1. tumorigenesis due to the combination of chronic inflammation and hypergastriemia associated with atrophic gastritis.
        2. achlorhydria due to:
          1. pernicious anemia
          2. Helicobacter pylori infection
  • Carcinoid Syndrome:
    • Enterochromaffin cells:
      • embryologically related to:
        • thyroid C cells
        • adrenal medullary cells
        • melanocytes
      • secrete many hormones, causing symptoms of hormone excess, including:
        1. cutaneous flushing, diarrhea, valvular heart disease (endocardial fibrosis --tricuspid insufficiency, pulmonary stenosis, right-sided heart failure}"classic triad"
        2. (less commonly): wheezing, paroxysmal hypotension, telangiectasis (spot formed on the skin by a dilated capillary or terminal artery)
    • Serotonin: most common secretory product (tumor serotonin synthesis from circulating tryptophan)
      • up to 50% of dietary tryptophan may be converted to serotonin by the tumor, leading insufficient amino acid substrate for protein synthesis and conversion to niacin. Consequently:
        • patients may exhibit protein malnutrition or
        • mild pellagra
          • (niacin deficiency -- erythema on portions of the body exposed to light, subsequent dermal exfoliation;also, weakness, digestive disturbance, spinal pain, convulsions, melancholia)
    • Diagnosis:
      • abdominal pain, nausea, weight loss, obstruction, gastrointestinal bleeding
      • imaging studies (CT, barium studies)
      • endoscopy
      • Most useful diagnostic test:serotonin metabolite (urinary 5-hydroxyindoleacetic acid {5-HIAA} concentration -- > 15 mg per day
      • plasma and platelet serotonin levels
      • biopsy
      • octreotide scintigraphy (octreotide binds to type 2 somatostatin receptors (highly expressed by most carcinoids)
    • Treatment:
      • tumor resection (rarely curative due to metastasis)
      • loperamide (Imodium), diphenoxylate (Lomotil)/atropine for mild diarrhea:
      • cholestyramine (Questran, Questran Light) (following ileal resection)
      • H1 and H2 receptor blockers (e.g. diphenhydramine (Benadryl) and  ranitidine (Zantac))-- inhibit cutaneous flushing.
      • phenoxybenzamine (Dibenzyline) -- inhibition of bradykinin release
      • methylxanthine bronchodilators and glucocorticoids: relief of dyspnea and wheezing due to pulmonary carcinoids
      • cyproheptadine (Periactin) and methysergide (Sansert): relief from diarrhea
        • note that methysergide can promote fibrosis (similar to that caused by the tumor)
      • Octreotide: potent inhibitor of carcinoid hormone secretion. Effective in:
        • treating life-threatening carcinoid syndrome manifestations, e.g.:
          1. hypotension with resulting angina.
          2. Transient exacerbation due to general anesthesia for example.
      • Systemic chemotherapy:
        • streptozocin (Zanosar),  fluorouracil (5-FU), cyclophosphamide (Cytoxan), dacarbazine (DTIC) and doxorubicin (Adriamycin) -- best response: combination of doxorubicin (Adriamycin) and streptozocin (Zanosar) {tumor regression in 40% of patients}
        • IFN-alpha
Kaplan, L,M. Endocrine Tumors of the Gastrointestinal Tract and Pancreas In Harrison's Principles of Internal Medicine 14th edition, (Isselbacher, K.J., and Braunwald, E., Wilson, J.D., Martin, J.B., Fauci, A.S. and Kasper, D.L., eds) McGraw-Hill, Inc (Health Professions Division), 1998, pp. 584-592.