Carcinoid syndrome
2557974
217343436
2008-06-05T16:52:41Z
SmackBot
433328
Date the maintenance tags or general fixes
{{DiseaseDisorder infobox |
Name = Carcinoid syndrome |
ICD10 = {{ICD10|E|34|0|e|20}} |
ICD9 = {{ICD9|259.2}} |
ICDO = {{ICDO|8240|3}}-8245 |
Image = |
Caption = |
OMIM = |
MedlinePlus = 000347 |
eMedicineSubj = med |
eMedicineTopic = 271 |
DiseasesDB = 2040 |
MeshID = D008303 |
}}
'''Carcinoid syndrome''' refers to the array of [[symptom]]s that occur secondary to [[carcinoid]] [[tumor]]s. Carcinoid tumors are discrete, yellow, well-circumscribed tumors that can occur anywhere along the [[gastrointestinal tract]] (GI) and in the lung. They most commonly affect the [[Vermiform appendix|appendix]], [[ileum]], and [[rectum]]. These tumors are unique in that they are [[endocrine]] in nature. They secrete [[hormone]]s into the [[blood stream]], which then travel to end [[Organ (anatomy)|organs]] and act upon them via appropriate receptors. Although quite rare with 15 cases/1,000,000 population, carcinoid tumors account for 75% of GI endocrine tumors.
==Clinical presentation==
Clinical findings include:<ref>E.Goljan, ''Pathology, 2nd ed'' Mosby Elsevier, Rapid Review series.</ref>
*[[Flushing (physiology)|Flushing]] of the skin
*[[Diarrhea]] and abdominal cramps
*[[Right heart|Right sided heart]] disease - fibrosis of the tricuspid valve
*[[Bronchoconstriction]]
*Abdominal pain due to [[desmoplasia|desmoplastic]] reaction of the [[mesentery]]
*In most patients, increased urinary excretion of 5-HIAA (5-hydroxyindoleacetic acid), a degradation product of [[serotonin]]
*Serotonin causes [[fibrosis]] of the [[tricuspid valve|tricuspid]] and [[pulmonary valve|pulmonary]] valves. Elevated levels of circulating serotonin have been associated with cardiac failure, due to fibrous deposits on the endocardium. These deposits are thought to be responsible for the fibrous degeneration of the valve apparatus.
**"TIPS" - Tricuspid Insufficiency, Pulmonic Stenosis (fibrosis of tricuspid and pulmonary valves)
{{Expand-section|date=June 2008}}
== Pathophysiology ==
Carcinoid tumors produce the vasoactive substance, [[serotonin]]. It is commonly, but incorrectly, thought that serotonin is the cause of the flushing. The flushing results from secretion of [[kallikrein]], the enzyme that catalyzes the conversion of kininogen to lysyl-bradykinin. The latter is further converted to [[bradykinin]], one of the most powerful [[vasodilators]] known. Other components of the carcinoid syndrome are diarrhea (probably caused by serotonin), a [[pellagra]]-like syndrome (probably caused by diversion of large amounts of tryptophan from synthesis of the vitamin B3, [[Niacin]], to the synthesis of 5-hydroxyindoles including serotonin), fibrotic lesions of the endocardium, particularly on the right side of the heart resulting in insufficiency of the tricuspid valve and, less frequently, the pulmonary valve and, uncommonly, bronchoconstriction. The pathogenesis of the cardiac lesions and the bronchoconstriction is unknown, but the former probably involves activation of serotonin [[5-HT2B receptor]]s by serotonin. When the primary tumor is in the gastrointestinal tract, as it is in the great majority of cases, the serotonin and kallikrein are inactivated in the liver; manifestations of carcinoid syndrome do not occur until there are [[metastases]] to the liver. Carcinoid tumors arising in the [[bronchi]] may be associated with manifestations of carcinoid syndrome without liver metastases because their biologically active products reach the systemic circulation before passing through the liver and being [[Drug metabolism|metabolized]].
== Diagnosis ==
With a certain degree of clinical suspicion, [[diagnosis]] is made primarily by measuring plasma levels of the secreted [[glycoprotein]] [[Chromogranin A]], supported by measuring the 24 hour [[urine]] levels of [[5-HIAA]] (5-hydroxyindoleacetic acid), a breakdown product of serotonin. Patients with carcinoid syndrome usually excrete >25 mg of 5-HIAA per day. For localization of both primary lesions and metastasis, the initial imaging method is Octreoscan, where <math>{}^{111}</math>Indium labelled [[somatostatin]] analogues ([[octreotide]]) are used in [[scintigraphy]] for detecting tumors expressing [[somatostatin]] receptors. Median detection rates with octreoscan are about 89%, in contrast to other imaging techniques such as [[CT scan]] and [[MRI]] with detection rates of about 80%. Usually on CT scan, one will note a spider-like/crab like change in the mesentery due to the fibrosis from the release of serotonin. PET scans, which evaluate for increased metabolism of glucose, may also aid in localizing the carcinoid lesion or evaluating for metastases.
== Localization of tumour ==
Tumour localization may be extremely difficult. Barium swallow and follow-up examination of the intestine may occasionally show the tumour. Capsule video endoscopy has recently been used to localize the tumour. Often [[laparotomy]] is the definitive way to localize the tumour.
== Treatment ==
For symptomatic relief of carcinoid sydrome:
*Octreotide (somatostatin analogue- neutralizes serotonin and decreases urinary 5-HIAA)
*Methysergide maleate (antiserotonin agent but not used because of serious side effect of retroperitoneal fibrosis)
*Cyproheptadine ([[antihistamine]])
Alternative treatment for qualifying candidates:
*[[Surgical]] resection of tumor and [[chemotherapy]] (5-FU and doxorubicin)
== Prognosis ==
[[Prognosis]] varies from individual to individual. It ranges from a 95% 5 year survival for localized disease to a 20% 5 year survival for those with liver metastases. The average survival time from the start of octreotide treatment has increased to about 12 years.
== Synonyms ==
*Thorson-Bioerck syndrome
*[[Staining (biology)#Silver staining|Argentaffinoma]] syndrome
*Cassidy-Scholte sydrome
*Flush syndrome
==References==
{{reflist}}
# "Endocrine Tumors of the GI Tract and Pancreas." Harrison's Manual of Medicine. Eugene Braunwald. 15th edition. New York: McGraw-Hill, 2002. 298-299.
# "Malignant Carcinoid Syndrome." Current Medical Diagnosis & Treatment. Lawrence M. Tierney, Jr. 43rd edition. New York: Lange Medical Books/McGraw-Hill, 2004. 1625.
# "Carcinoid Syndrome." Griffith's 5 Minute Clinical Consult. Mark Dambro. Mobile Version 6.0.139. Lippincott, Williams and Wilkins, 2003.
# "Current Status of Gastrointestinal Carcinoids." Gastroenterology. Irvin M. Modlin et al. 2005;128;1717-1751.
==See also==
* [[Kulchitsky cells]]
==External links==
* [http://www.caringforcarcinoid.org Caring for Carcinoid Foundation]
* [http://www.carcinoidsyndrome.net Carcinoid Syndrome]
* [http://www.merck.com/mrkshared/mmanual/section2/chapter17/17b.jsp Merck]
* http://www.carcinoid.org
{{Endocrine pathology}}
[[Category:Gastroenterology]]
[[Category:Endocrinology]]
[[Category:Cardiology]]
[[de:Flush-Syndrom]]