Carcinoid syndrome

For patient information click here

Overview
Carcinoid syndrome refers to the array of symptoms that occur secondary to carcinoid tumors. Carcinoid tumors are discrete, yellow, well-circumscribed tumors that can occur anywhere along the gastrointestinal tract (GI). They most commonly affect the appendix, ileum, and rectum. These tumors are unique in that they are endocrine in nature. They secrete hormones into the blood stream, which then travel to end organs and act upon them via appropriate receptors. Although quite rare, 15 cases/1,000,000 population, carcinoid tumors account for 75% of GI endocrine tumors.

Clinical presentation
Clinical findings include:
 * Flushing of the skin
 * Diarrhea and abdominal cramps
 * Right sided heart disease
 * bronchoconstriction
 * abdominal pain due to desmoplastic reaction of the mesentery
 * in most patients, increased urinary excretion of 5-HIAA (5-hydroxyindoleacetic acid), a degradation product of serotonin
 * Serotonin causes fibrosis of the tricuspid valve and pulmonary valve
 * "TIPS" - Tricuspid Insufficiency, Pulmonic Stenosis (fibrosis of tricuspid and pulmonary valves)

Pathophysiology
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 serotonin), a pellagra-like syndrome (probably caused by diversion of large amounts of tryptophan from synthesis of the vitamin, niacin, to the synthesis of 5-hydroxyindoles including serotonin), 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. 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. Carcinoid tumors arising in the bronchi, because their biologically active products reach the systemic circulation before passing through the liver, may be associated with manifestations of carcinoid syndrome without liver metastases.

Diagnosis
With a certain degree of clinical suspicion, diagnosis is made primarily by measuring plasma levels of the secreted glycoprotein Chromogranin A, supported by measuring the 24 hour urine levels of 5-HIAA (5-hydroxyindoleacetic acid), a breakdown product of serotonin. Patients with carcinoid syndrome usually excrete >25 mg of 5-HIAA per day. For localization of both primary lesions and metastasis, the initial imaging method is Octreoscan, where $${}^{111}$$Indium 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 scans and MRI with detection rates of about 80%. Usually on CT scan, one will note a spider-like/crab like change in the messentery due to the fibrosis from the release of serotonin. PET scans, which evaluate for increased metabolism of glucose, may also aid in localizing the carcinoid lesion or evaluating for metastases.

Localization of tumur
Tumour localization may be extremely difficult, Barium swallow and follow-up examination of the intestine may occasionally show the tumour. Capsule video endoscopy has recently been used to localized the tumour. Often laparotomy is the definitive way to localize the tumour.

Treatment
For symptomatic relief of carcinoid sydrome: Alternative treatment for qualifying candidates:
 * Octreotide (somatostatin analogue- neutralizes serotonin and decreases urinary 5-HIAA)
 * Methysergide maleate (antiserotonin agent but not used because of serious side effect of retroperitoneal fibrosis)
 * Cyproheptadine (antihistamine)
 * Surgical resection of tumor and chemotherapy (5-FU and doxorubicin)

Prognosis
Prognosis varies from individual to individual. It ranges from a 95% 5 year survival for localized disease to a 20% 5 year survival for those with liver metastases. The average survival time from the start of octreotide treatment has increased to about 12 years.

Synonyms
Thorson-Bioerck syndrome, argentaffinoma syndrome, Cassidy-Scholte sydrome, flush syndrome