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, vomiting 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. If the primary tumor is from the gastrointestinal 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 several vasoactive substances, most prominently serotonin. It is commonly thought that serotonin is the cause of the flushing, but this is only partially correct. The flushing also 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.

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.

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.

Regards
Amalia
Managing Editor
Journal of clinical Oncology and Cancer Research