Carcinoid syndrome

Published on 02/03/2015 by admin

Filed under Endocrinology, Diabetes and Metabolism

Last modified 22/04/2025

Print this page

rate 1 star rate 2 star rate 3 star rate 4 star rate 5 star
Your rating: none, Average: 0 (0 votes)

This article have been viewed 2047 times

CHAPTER 54

Carcinoid syndrome

1. What are carcinoid tumors? How are they classified?

2. Define carcinoid syndrome.

3. What are the biochemical mediators of carcinoid syndrome?

4. Why does pellagra often accompany carcinoid syndrome?

5. Why do intestinal carcinoid tumors so infrequently cause carcinoid syndrome?

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.

7. How is the diagnosis of carcinoid syndrome usually made?

The diagnosis is made by finding markedly elevated urinary excretion of 5-hydroxyindoleacetic acid (5-HIAA), a breakdown product of serotonin (see Fig. 54-2). Normal urinary 5-HIAA excretion is less than 8 mg/24 hours. Malabsorption syndromes, ingestion of tryptophan-rich foods, and use of certain medications can elevate urinary 5-HIAA, but the value usually remains lower than 30 mg/24 hours (Table 54-1). Carcinoid syndrome is most often associated with urinary 5-HIAA excretion greater than 100 mg/24 hours, although mild or no elevation may be seen in some patients.

TABLE 54-1.

NONCARCINOID CAUSES OF ABNORMAL 5-HYDROXYINDOLEACETIC ACID EXCRETION

Diseases: malabsorption disorders

Food (tryptophan rich) : bananas, pineapples, kiwi, plums, avocados, eggplant, pecans, walnuts, hickory nuts

Medications that increase 5-HIAA : acetaminophen, ephedrine, guaifenesin, mephenesin, methocarbamol, phenacetin, caffeine, nicotine, methamphetamine, phenobarbital, acetanilid, reserpine, phentolamine, phenmetrazine, coumaric acid, melphalan, fluorouracil

Medications that decrease 5-HIAA : aspirin, ethanol, heparin, imipramine, levodopa, methyldopa, monoamine oxidase inhibitors, phenothiazines, isoniazid, corticotropin, gentisic acid, methenamine, streptozotocin

5-HIAA, 5-Hydroxyindoleacetic acid.

8. How is carcinoid syndrome diagnosed if urinary 5-HIAA is normal?

Foregut carcinoid tumors often lack the enzyme L-amino acid decarboxylase and therefore do not make serotonin or 5-HIAA (see Fig. 54-2). Chromogranin A, a sensitive but nonspecific marker of neuroendocrine tumors, is a good alternative test. Mild elevations may occur in many conditions (Table 54-2), but values greater than 31 U/L have 75% sensitivity and 84% specificity for diagnosing carcinoid syndrome. Whole blood serotonin and NSE, when available, may also be helpful in equivocal cases.

TABLE 54-2.

CAUSES OF ELEVATED SERUM CHROMOGRANIN A

Neuroendocrine disorders: carcinoid tumors, pheochromocytoma, islet cell tumors, medullary carcinoma of the thyroid, neurofibromatosis

Other conditions: prostate cancer, hyperthyroidism, renal failure, heart failure, hypertension, atrophic gastritis

Medications: proton pump inhibitors

9. What procedures are best to localize the source of carcinoid syndrome?

10. What is the treatment for carcinoid syndrome?

11. How does one control carcinoid syndrome symptoms?

The most troublesome symptoms patients with carcinoid syndrome experience are intense flushing and frequent diarrhea. Somatostatin analogs (octreotide, lanreotide) are often highly effective in controlling carcinoid symptoms. Other antiflushing and antidiarrheal strategies can be added if symptom control is inadequate. Table 54-3 lists various medication options for relief of refractory symptoms. Hepatic resection can be very effective in patients with focal liver metastases. Other options include hepatic artery embolization, chemoembolization, 90-Y microsphere radioembolization, radiolabeled somatostatin analog therapy, and alpha-interferon.

12. What chemotherapy regimens are most effective in carcinoid tumors?

13. What is a carcinoid crisis?

14. How can a carcinoid crisis be prevented?

15. Can a carcinoid crisis be predicted?

Patients with carcinoid tumors who have not developed carcinoid syndrome can be tested for their potential to have a carcinoid crisis. This is most commonly accomplished with an epinephrine provocation test; patients are given progressive intravenous (IV) boluses of epinephrine every 5 minutes, starting with a dose of 1 μg and increasing, if necessary, to 10 μg, while heart rate and blood pressure are monitored every 60 seconds. A positive response consists of flushing or a blood pressure drop of 20 mm Hg systolic or 10 mm Hg diastolic 45 to 120 minutes after an injection. All patients undergoing this test must have venous catheters and be monitored carefully throughout the test; IV phentolamine (Regitine) 5-mg and methoxamine (Vasoxyl) 3-mg preparations must also be available to reverse a crisis should it occur.

16. Describe the management of a carcinoid crisis.

Effective treatment for carcinoid crisis consists of IV administration of octreotide and glucocorticoids. If this does not abort the episode, additional options include methotrimeprazine (an antiserotonin agent), methoxamine (a direct vasoconstrictor), phentolamine (an alpha-adrenergic blocker), ondansetron (a serotonin receptor antagonist), and glucagon. It is critical to avoid the use of adrenergic and sympathomimetic agents in patients with suspected carcinoid crisis because these drugs can significantly worsen the condition. Effective medication dose regimens for this condition are listed in Table 54-4.

TABLE 54-4.

MANAGEMENT OF CARCINOID CRISIS

MEDICATION DOSE REGIMEN
Octreotide (Sandostatin) 50 μg IV over 1 min, then 50 mg IV over 15 min
Hydrocortisone (Solu-Cortef) 100 mg IV over 15 min
Methotrimeprazine (Levoprome) 2.5-5.0 mg slow IV push
Methoxamine (Vasoxyl) 3-5 mg slow IV push, followed by an infusion
Phentolamine (Regitine) 5 mg slow IV push
Ondansetron (Zofran) 20 mg IV over 15 min
Glucagon 0.5-1.5 mg slow IV push

IV, Intravenous.

From Warner RRP: Gut neuroendocrine tumors. In Bardin CW, editor: Current therapy in endocrinology and metabolism, ed 6, St. Louis, 1997, Mosby, pp 606–614.

Bibliography

Baudin, E, Gastroenteropancreatic endocrine tumors. clinical characterization before therapy. Nat Clin Pract Endocrinol Metab 2007;3:228–238.

Campana, D, Nori, F, Piscitelli, L, et al, Chromogranin A. is it a useful marker of neuroendocrine tumors. J Clin Oncol 2007;25:1963–1967.

Eriksson, B, Kloppel, G, Krenning, E, et al, Consensus guidelines for the management of patients with digestive neuroendocrine tumors. well differentiated jejunal-ileal tumor/carcinoma. Neuroendocrinology 2008;87:8–19.

Feldman, JM. The carcinoid syndrome. Endocrinologist. 1993;3:129–135.

Galanis, E, Kvols, LK, Rubin, J. Carcinoid syndrome. J Clin Oncol. 1998;16:796–798.

Koopmans, KP, Neels, OC, Kema, IP, et al. Improved staging of patients with carcinoid and islet cell tumors with 18F-dihydroxy-phenyl-alanine and 11C-5-hydroxy-tryptophan positron emission tomography. J Clin Oncol. 2008;26:1489–1495.

Maggard, MA, O’Connell, JB, Ko, CY. Updated population-based review of carcinoid tumors. Ann Surg. 2004;240:117–122.

Modlin, IM, Lye, KD, Kidd, M. A 5-decade analysis of 13,715 carcinoid tumors. Cancer. 2003;97:934–959.

Moldin, IM, Oberg, K, Chung, CD, et al. Gastroenteropancreatic neuroendocrine tumors. Lancet Oncol. 2008;9:61–72.

O’Toole, D, Ducreaux, M, Bommelaer, G, et al, Treatment of carcinoid syndrome. a prospective crossover evaluation of lanreotide versus octreotide in terms of efficacy, patient acceptability, and tolerance. Cancer 2000;88:770–776.

Plockinger, U, Wiedenmann, B. Management of metastatic endocrine tumors. Best Pract Res Clin Gastroentero. 2005;19:553–576.

Soga, J, Yakuwa, Y, Osaka, M, Carcinoid syndrome. a statistical evaluation of 748 reported cases. J Exp Clin Cancer Res 1999;18:133–141.

Stuart, K, Levy, DE, Anderson, T, et al, Phase II study of interferon gamma in malignant carcinoid tumors (E9292). a trial of the Eastern Oncology Group. Invest New Drugs 2004;22:75–81.