Carcinoid syndrome
1. What are carcinoid tumors? How are they classified?
Carcinoid tumors are neoplasms that arise from enterochromaffin cells. They are classified according to their site of origin as foregut (bronchus, stomach, duodenum, bile ducts, pancreas), midgut (jejunum, ileum, appendix, ascending colon), or hindgut (transverse and descending colon, rectum) carcinoids. They also develop in the ovaries, testes, prostate, kidney, breast, thymus, or skin. Approximately 55% of carcinoid tumors occur in the gastrointestinal (GI) tract, and 30% are found in the bronchopulmonary system. Of those tumors in the GI tract, the location frequencies are as follows: small intestine (45%, most commonly the ileum), rectum (20%), appendix (16%), colon (11%), and stomach (7%).
Carcinoid syndrome is a humorally mediated disorder consisting of cutaneous flushing (90%), diarrhea (75%), bronchospasm (20%), endocardial fibrosis (33%), right-sided heart valvular lesions, and occasionally pleural, peritoneal, or retroperitoneal fibrosis.
3. What are the biochemical mediators of carcinoid syndrome?
Carcinoid tumors produce a variety of humoral mediators, including serotonin, chromogranin A, neuron-specific enolase (NSE), histamine, prostaglandins, bradykinin, tachykinins, neurotensin, motilin, and substance P. Diarrhea and fibrous tissue formation may be caused by serotonin, whereas flushing and wheezing are likely the result of histamine, prostaglandins, or kinins (Fig. 54-1). The formation and metabolism of serotonin are shown in Figure 54-2.
Figure 54-1. Carcinoid syndrome.
Figure 54-2. Serotonin metabolism.
4. Why does pellagra often accompany carcinoid syndrome?
Pellagra is caused by niacin deficiency that results when a carcinoid tumor diverts large amounts of tryptophan from niacin synthesis to produce serotonin (see Fig. 54-2).
5. Why do intestinal carcinoid tumors so infrequently cause carcinoid syndrome?
Carcinoid syndrome occurs when humoral mediators enter the systemic circulation in large quantities. Solitary intestinal carcinoids secrete mediators into the portal circulation, where they are almost totally metabolized by the liver and never reach the systemic circulation. Carcinoid syndrome does not usually occur with these tumors unless the patient has hepatic metastases that impair mediator metabolism or that secrete mediators directly into the hepatic vein. Extraintestinal carcinoids, however, may cause carcinoid syndrome in the absence of metastases because they secrete mediators into venous systems that do not first pass through the liver.
6. Do carcinoid tumors cause any other humoral syndromes?
Carcinoids may also secrete corticotropin-releasing factor (CRF) or corticotropin (adrenocorticotropin [ACTH]), thus causing Cushing’s syndrome, or growth hormone–releasing factor (GRF), thus causing acromegaly. These syndromes have been reported mainly with bronchial and pancreatic carcinoid tumors.
KEY POINTS 1: CARCINOID SYNDROME
1. Carcinoid syndrome results from tumor production of humoral mediators that cause flushing, diarrhea, bronchospasm, and fibrous tissue formation.
2. Most patients with carcinoid syndrome have extensive liver metastases that either impair the metabolic clearance of mediators secreted by the primary tumor or secrete the mediators directly into the hepatic vein.
3. Carcinoid syndrome is diagnosed by demonstrating markedly increased urinary excretion of 5-hydroxyindoleacetic acid (5-HIAA) or elevated levels of serum chromogranin A or whole blood serotonin.
4. The treatment for carcinoid syndrome is surgery, when possible, or palliation of symptoms by giving medications that reduce secretion of the humoral mediators or antagonize their effects.
5. A carcinoid crisis can be precipitated when a patient with a carcinoid tumor is given an adrenergic or sympathomimetic medication or a monoamine oxidase (MAO) inhibitor.
6. A carcinoid crisis is best treated with intravenous octreotide and hydrocortisone and avoidance of adrenergic and sympathomimetic agents.
7. How is the diagnosis of carcinoid syndrome usually made?
