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carcinoid syndrome

Etiology: - syndrome resulting from release of neuroendocrine agents & other hormones from enterochromaffin cells (carcinoid) - pulmonary carcinoid neoplasms or malignant carcinoid metastatic to the liver Epidemiology: -> peak incidence is in the 6th decade of life. Pathology: 1) release neuroendocrine agents from tumor cells a) serotonin b) bradykinin c) kallikrein d) histamine e) prostaglandin f) tachykinins 1] neuropeptide K 2] substance P 2) release of other hormones a) gastrin b) ACTH c) insulin d) glucagon e) somatostatin f) chorionic gonadotropin g) vasoactive intestinal polypeptide (VIP) h) motilin i) calcitonin 3) atypical carcinoid variants a) may be deficient in dopa-decarboxylase b) may secrete 5-hydroxytryptophan 4) cardiac - tricuspid valve & pulmonic valve thickening & stenosis - excess serotonin can lead to fibrosis or the tricuspid valve & pulmonic valve - endocardial fibrosis [5] 5) hepatomegaly [5] 6) retroperitoneal fibrosis [5] 7) pelvic fibrosis [5] Clinical manifestations: 1) 5% of patients with carcinoid tumors manifest carcinoid syndrome 2) carcinoid triad a) flushing b) diarrhea c) right-sided heart failure 3) paraneoplastic manifestations a) associated with release neuroendocrine agents from tumor cells (see pathology) b) skin manifestations 1] episodic skin flushing 2] telangiectasias 3] pellagra dermatosis (tryptophan depletion from 5-HT synthesis) 4] cyanosis c) gastrointestinal manifestations - abdominal cramps - nausea/vomiting - diarrhea d) hypotension e) pulmonary manifestations - bronchoconstriction, bronchospasm - wheezing, cough dyspnea [5] f) cardiac valvular dysfunction 1] tricuspid regurgitation (most common) 2] pulmonic valvular regurgitation 3] pulmonic valvular stenosis 4] mitral insufficiency [5] 5] aortic insufficiency [5] g) cardiac arrhythmias [5] 4) small bowel obstruction may occur Laboratory: 1) elevated 24 hour urine 5-hydroxy-indoleacetic acid (5-HIAA) a) acidify to pH of 2-3 with 10 mL of 6N HCl b) normal 2-8 mg 5-HIAA/24 hours c) false positives with foods high in tryptophan or serotonin: bananas, plantains, tomatoes, eggplant, pineapple, kiwi, walnuts, hickory note, pecans, avocados d) false negative with patients taking reserpine, salicylates, MAO inhibitors, phenothiazines, L-dopa 2) eelevated blood 5-hydroxy-indoleacetic acid (5-HIAA) a) whole blood or platelet rich plasma b) collect in EDTA tube containing ascorbate c) most serotonin in blood is stored in platelets d) reference interval 1] 50-200 ng/mL (whole blood) 2] 125-500 mg/mL (platelet-rich plasma) 3) 5-hydroxytryptophan in blood or urine Radiology: 1) as indicated by signs/symptoms 2) useful studies may include: a) abdominal CT b) endoscopy c) barium enema d) enteroclysis e) upper GI with small bowel follow through 3) bone scans 4) echocardiography 5) octreotide scintigraphy a) octreotide binds type 2 somatostatin receptors b) type 2 somatostatin receptors expressed in large numbers by most carcinoid tumors c) identifies primary & metastatic tumor in 2/3 of patients Management: 1) symptomatic treatment a) antihistamines (H1 & H2) 1] ranitidine 2] diphenhydramine b) phenoxybenzamine may inhibit release of bradykinin c) glucocorticoids may help relieve bronchospasm & wheezing d) octreotide inhibits tumor growth & hormone secretion by carcinoid cells 1] 150-1500 ug/day 2] control of diarrhea, flushing, wheezing 3] long-acting IM form for monthly injection 2) successful treatment of underlying malignancy results in resolution of symptoms [4] a) chemotherapeutic protocols 1] doxorubicin 2] streptozocin b) surgery 3) prognosis a) carcinoid tumors 1] 95% 5-year survival with local disease 2] 65% 5-year survival with lymph node involvement 3] 20% 5-year survival with liver metastases b) median survival is 2.5 years with carcinoid syndrome c) overall 18% 5 year survival without treatment v) overall 67% 5 year survival after introduction of octreotide

Interactions

disease interactions

Related

carcinoid (argentaffinoma) octreotide (Sandostatin)

General

paraneoplastic syndrome

Properties

ASSOCIATED-NEOPLASM[S]: carcinoid

References

  1. Clinical Diagnosis & Management by Laboratory Methods, 19th edition, J.B. Henry (ed), W.B. Saunders Co., Philadelphia, PA. 1996, pg 533-35
  2. Mayo Internal Medicine Board Review, 1998-99, Prakash UBS (ed) Lippincott-Raven, Philadelphia, 1998, pg 55
  3. Harrison's Principles of Internal Medicine, 14th ed. Fauci et al (eds), McGraw-Hill Inc. NY, 1998, pg 585, 587
  4. Medical Knowledge Self Assessment Program (MKSAP) 16, 17, 19. American College of Physicians, Philadelphia 2012, 2015, 2021
  5. Ahmad A (slide show) Carcinoid Tumors: Cancers in Slow Motion. Medscape. March 30, 2016 http://reference.medscape.com/features/slideshow/carcinoid-tumors