Carcinoid syndrome

Carcinoid syndrome
Serotonin
Classification and external resources
Specialty	endocrinology
ICD-10	E34.0
ICD-9-CM	259.2
ICD-O	M8240/3-8245
DiseasesDB	2040
MedlinePlus	000347
eMedicine	med/271
MeSH	D008303
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Carcinoid syndrome is a paraneoplastic syndrome comprising the signs and symptoms that occur secondary to carcinoid tumors. The syndrome includes flushing and diarrhea, and, less frequently, heart failure and bronchoconstriction. It is caused by endogenous secretion of mainly serotonin and kallikrein.

The carcinoid syndrome occurs in approximately 5% of carcinoid tumors and becomes manifest when vasoactive substances from the tumors enter the systemic circulation escaping hepatic degradation. Interestingly, if the primary tumor is from the GI tract (hence releasing serotonin into the hepatic portal circulation), carcinoid syndrome generally does not occur until the disease is so advanced that it overwhelms the liver's ability to metabolize the released serotonin.

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 the increased serotonin, which increases peristalsis, leaving less time for fluid absorption), a pellagra-like syndrome (probably caused by diversion of large amounts of tryptophan from synthesis of the vitamin B₃niacin, which is needed for NAD production, to the synthesis of serotonin and other 5-hydroxyindoles), 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.

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