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definition - Carcinoid_syndrome

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Carcinoid syndrome

                   
Carcinoid syndrome
Classification and external resources

Serotonin
ICD-10 E34.0
ICD-9 259.2
ICD-O: M8240/3-8245
DiseasesDB 2040
MedlinePlus 000347
eMedicine med/271
MeSH D008303

Carcinoid syndrome refers to the array of symptoms that occur secondary to carcinoid tumors.[1] The syndrome includes flushing and diarrhea, and, less frequently, heart failure and bronchoconstriction.[2] It is caused by endogenous secretion of mainly serotonin and kallikrein.

Contents

  Clinical presentation

  Presentation of the carcinoid syndrome.[3]

The carcinoid syndrome occurs in approximately 10% of carcinoid tumors[4] and becomes manifest when vasoactive substances from the tumors enter the systemic circulation escaping hepatic degradation. This is the case when carcinoid tumors metastasize to the liver or they arise for example in the bronchus.

The most important clinical finding is flushing of the skin, usually of the head and the upper part of thorax.[5] Secretory diarrhea and abdominal cramps are also characteristic features of the syndrome. When the diarrhea is intensive it may lead to electrolyte disturbance and dehydration. Other associated symptoms are nausea, and vomiting. Bronchoconstriction, which may be histamine-induced, affects a smaller number of patients and often accompanies flushing.

About 50% of patients have cardiac abnormalities, caused by serotonin-induced fibrosis of the tricuspid and pulmonary valves, called cardiac fibrosis. 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" is an acronym for Tricuspid Insufficiency, Pulmonary Stenosis (fibrosis of tricuspid and pulmonary valves).

Abdominal pain is due to desmoplastic reaction of the mesentery or hepatic metastases.

Although the most common site of a carcinoid tumor is the appendix or terminal ileum, liver metastases, releasing serotonin directly into the systemic circulation are required for the carcinoid syndrome to occur. This is because serotonin created by a GI carcinoid tumour and released into the hepatic portal system is broken down at the liver and does not reach the systemic circulation. Serotonin is also metabolized in the lungs. However: If the tumor is bronchogenic in origin, then metastasis does not need to occur in order for carcinoid syndrome to occur.

  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 receptors 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 or when the cancer is accompanied by liver failure (cirrhosis). 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 metabolized.

In most patients, there is an increased urinary excretion of 5-HIAA (5-hydroxyindoleacetic acid), a degradation product of serotonin.

The biology of these tumors is interesting as it differs from many other tumor types. Ongoing research on the biology of these tumors may reveal new mechanisms for tumor development[6]

  Diagnosis

With a certain degree of clinical suspicion, the most useful initial test is the 24 hour urine levels of 5-HIAA (5-hydroxyindoleacetic acid), the end product of serotonin metabolism. Patients with carcinoid syndrome usually excrete more than 25 mg of 5-HIAA per day. For localization of both primary lesions and metastasis, the initial imaging method is Octreoscan, where indium-111 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%. Gallium-68 labelled somatostatin analogues such as 68Ga-DOTA-Octreotate (DOTATATE), performed on a PET/CT scanner is superior to conventional Octreoscan. 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. 18F-FDG PET/CT, which evaluate for increased metabolism of glucose, may also aid in localizing the carcinoid lesion or evaluating for metastases. Chromogranin A and platelets serotonin are increased.

  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.

  Primary site of a carcinoid cancer of gut, secondaries are also visible on the mesentery

  Treatment

For symptomatic relief of carcinoid syndrome:

Alternative treatment for qualifying candidates:

  • Surgical resection of tumor and chemotherapy (5-FU and doxorubicin)
  • Endovascular, Chemoembolization, targeted chemotherapy directly delivered to the liver through special catheters mixed with embolic beads (particles that block blood vessels). For patients with liver metastases.
  Uncertainties

All aspects of this disease have significant uncertainties. Patients frequently face disagreeing doctors and have to choose which doctors' advice to follow, thereby effectively deciding their own treatment course. Disease progression is difficult to ascertain because the disease can metastasize anywhere in the body, can be too small to identify with any current technology, and surprises can await the surgeon in the operating room. The markers, such as Chromogranin A, are generally poor signifiers. Therefore, the patient and doctor must make decisions with few facts and few ways to test the results of those decisions.

  Prognosis

Prognosis varies from individual to individual. It ranges from a 95% 5 year survival for localized disease to an 80% 5 year survival for those with liver metastases.[citation needed] The average survival time from the start of octreotide treatment has increased to about 12 years.[citation needed]

  Synonyms

  • Thorson-Bioerck syndrome
  • Argentaffinoma syndrome
  • Cassidy-Scholte sydrome
  • Flush syndrome

  References

  1. ^ "carcinoid syndrome" at Dorland's Medical Dictionary
  2. ^ [http://www.internetmedicin.se/dyn_main.asp?page=1515 internetmedicin.se > Carcinoider, gastrointestinala (gastrointestinal carcinoids). By Eva Tiensuu Janson. Retrieved Nov 2010
  3. ^ Table 15-14 in: Mitchell, Richard Sheppard; Kumar, Vinay; Abbas, Abul K.; Fausto, Nelson. Robbins Basic Pathology. Philadelphia: Saunders. ISBN 1-4160-2973-7.  8th edition.
  4. ^ Warrell et al. (2003). Oxford Textbook of Medicine (4th ed.). Oxford University Press. ISBN 0-19-262922-0. 
  5. ^ E.Goljan, Pathology, 2nd ed Mosby Elsevier, Rapid Review series.
  6. ^ JL Cunningham and ET Janson The Hallmarks of Ileal Carcinoids (Eur J Clin Invest 2011; 41 (12): 1353–1360) http://onlinelibrary.wiley.com/doi/10.1111/j.1365-2362.2011.02537.x/abstract

  See also

   
               

 

All translations of Carcinoid_syndrome


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