Neuroendocrine Tumours and Carcinoid Syndrome

Carcinoid syndrome is a clinical constellation of symptoms caused by the systemic release of vasoactive substances -- primarily serotonin (5-hydroxytryptamine/5-HT), histamine, kallikrein, prostaglandins, and tachykinins -- from neuroendocrine tumors (NETs, formerly called carcinoid tumors). Neuroendocrine tumors arise from enterochromaffin cells, which are part of the diffuse neuroendocrine system scattered throughout the gastrointestinal tract, bronchopulmonary system, and other organs. These cells normally produce and store serotonin and other bioactive amines in dense-core secretory granules. Serotonin synthesis begins with the essential amino acid tryptophan, which is hydroxylated by tryptophan hydroxylase to 5-hydroxytryptophan (5-HTP), then decarboxylated by aromatic L-amino acid decarboxylase (AADC) to serotonin (5-HT). In patients with large tumor burdens, carcinoid tumors can consume up to 60% of dietary tryptophan for serotonin synthesis, potentially causing tryptophan deficiency. Since tryptophan is also the precursor for niacin (vitamin B3) synthesis, tryptophan depletion can produce pellagra (the 4 Ds: dermatitis, diarrhea, dementia, and if untreated, death) -- this is an important but often overlooked complication of advanced carcinoid syndrome. A critical concept for understanding why carcinoid syndrome typically requires hepatic metastases is first-pass hepatic metabolism....