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Carcinoid syndrome

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. more...

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Pathophysiology

Carcinoid tumors secrete vasoactive substances such as serotonin, histamine, catecholamines, and prostaglandins. These hormones acts upon many tissues of the body including the central nervous system, blood vessels of the intestinal tract, and platelets, ultimately altering blood flow. Prior to metastasis, the liver is capable of metabolizing most of the hormones elaborated by such tumors, rendering patients asymptomatic. Only about 5% of patients with carcinoid tumors ever develop symptoms of the carcinoid syndrome which includes, flushing, diarrhea, hypotension, edema, asthma-like bronchoconstriction attacks, and valvular heart disease. The onset of these symptoms suggests that the tumor has metastasized to the liver, allowing serotonin and its various by-products to reach systemic circulation.

Diagnosis

With a certain degree of clinical suspicion, diagnosis is made 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.

Treatment

For symptomatic relief of carcinoid sydrome:

  • 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)

Alternative treatment for qualifying candidates:

  • 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. However, median survival for patients with carcinoid sydrome is 2.5 years from the first episode of flushing.

Synonyms

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

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Carcinoid-Related Intrapulmonary Shunting May Be Associated With Increased Production of Nitric Oxide
From CHEST, 12/1/99 by Shinji Teramoto

To the Editor:

In a recent issue of CHEST, Lee and Lepler (April 1999)[1] rationally discussed the mimicking of hepatopulmonary syndrome (HPS) by the severe intrapulmonary shunting that is caused by carcinoid syndrome.

HPS is caused by hypoxemia in patients with chronic liver diseases in the absence of intrinsic lung disease,[2] and so carcinoid-related intrapulmonary shunting and hypoxemia are not exactly the same as HPS. However, HPS may occur secondary to a functional right-to-left shunt because of intrapulmonary vascular dilatation.[3] Thus, the shunting in that situation may mimic the pathogenesis of HPS in carcinoid syndrome. Furthermore, recent evidence suggests that nitric oxide (NO) is an important mediator of impaired oxygenation in patients with cirrhosis (ie, HPS).[4,5] The increased production of NO by metastatic carcinoid tumors in the lung may be another cause of extraordinary vasodilation and intrapulmonary shunting, resulting in severe hypoxemia in carcinoid syndrome.

Patients with carcinoid syndrome are known to produce the vasoconstrictor 5-hydroxytryptamine. However, NO, a major vasodilator, also may be produced in patients with carcinoid syndrome.[6] Although carcinoid-related pulmonary shunting may be responsible for hypoxemia in the case of the patient reported by Lee and Lepler who has metastatic carcinoid tumors, the pathogenic mechanism of severe hypoxemia may not be simple in carcinoid syndrome. Because many neurohumoral vasoactive substances can be released by tumors, the complex regulatory mechanism may work in the lungs of the patients. Further analysis of vasodilators and vasoconstrictors may be important to elucidate the mechanism of hypoxemia in the carcinoid syndrome.

Shinji Teramoto, MD, FCCP Takeshi Matsuse, MD Yasuyoshi Ouchi, MD Tokyo University Hospital Tokyo, Japan

Correspondence to: Shinji Teramoto, MD, FCCP, Department of Geriatric Medicine, Tokyo University Hospital, 7-3-1 Hongo Bunkyo-ku, Tokyo, Japan 113-8655

REFERENCES

[1] Lee DF, Lepler LS. Severe intrapulmonary shunting associated with metastatic carcinoid. Chest 1999; 115:1203-1206

[2] Krowka MJ, Cortese DA. Hepatopulmonary syndrome: current concepts in diagnosis and therapeutic considerations. Chest 1994; 105:1528-1537

[3] Whyte MK, Hughes JM, Peters AM, et al. Analysis of intrapuhnonary right to left shunt in the hepatopulmonary syndrome. J Hepatol 1998; 29:85-93

[4] Teramoto S, Matsuse T, Ouchi Y. Nitric oxide and impaired oxygenation before and after liver transplantation [letter]. Ann Intern Med 1999; 131:69

[5] Rolla G, Brussino L, Colagrande P, et al. Exhaled nitric oxide and oxygenation abnormality in hepatic cirrhosis. Hepatology 1997; 26:842-847

[6] Hansen MB, Dresner LS, Wait RB. Profile of neurohumoral agents on mesenteric and intestinal blood flow in health and disease. Physiol Res 1998; 47:307-327

COPYRIGHT 1999 American College of Chest Physicians
COPYRIGHT 2000 Gale Group

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