Etiology and Pathophysiology Functioning tumors of the diffuse peripheral endocrine or paracrine system produce various amines and polypeptides with corresponding signs and symptoms, including carcinoid syndrome. Carcinoid syndrome is usually associated with functioning malignant tumors that produce serotonin and arise from enteroendocrine cells in the ileum, but it can occur with comparable tumors elsewhere in the GI tract, pancreas, gonads, or bronchi. Rarely, certain highly malignant tumors may also be responsible, including oat cell carcinoma of the lung, pancreatic islet cell carcinoma, and medullary carcinoma of the thyroid gland. Hepatic metastases, however, release metabolic products via the hepatic veins directly into the systemic circulation. Primary pulmonary and ovarian carcinoid products bypass the portal route and may similarly induce symptoms, as can rare intestinal carcinoids with only intra-abdominal spread that drain directly into the systemic circulation or the lymphatics.
Serotonin acts on smooth muscle to produce diarrhea, colic, and malabsorption.
Histamine and bradykinin, through their vasodilator effects, cause flushing. The most common and often earliest sign is an uncomfortable flushing, typically of the head and neck, often precipitated by emotion or the ingestion of food, hot water, or alcohol. Striking skin color changes may occur, ranging from pallor or erythema to cyanosis. Abdominal cramps with recurrent diarrhea occur and are often the patient's major complaint. Malabsorption syndrome has been documented in some cases.