Carcinoid Syndrome (1)

This unfortunate lady has Carcinoid Syndrome. It is speculated that this lesion doesn't start to cause symptoms until it is metastatic to the liver. This explains the patients hepatomegaly. Metastatic disease to the liver is necessary because the liver is a good metabolizer of 5-HT (serotonin) the active agent that causes all of a patients symptoms. To get systemic effects it must get past the liver. Further evidence of metastatic disease is exhibited by the murmur of tricuspid insufficiency. This is speculated to occur secondary to high serotonin levels affecting the tricuspid valve causing significant valvular insufficiency (3) as is exemplified by the pulsatile liver on examination. Finally, a further sign of metastatic disease is the evidence of lung parenchymal disease as suggested by the symptoms of wheezing. Again this is presumed hematogenous seeding from the liver, through the right side of heart and finally into the lung (2).

Most carcinoid's can be picked up with a urine collection for 5-hydroxyindoleacetic acid (5-HIAA) which is a metabolite of serotonin (5). Usually, serum serotonin levels are also elevated. However, many gastric carcinoid tumors lack the aromatic L-amino acid decarboxylase and convert 5-hydroxytryptophan to serotonin with low efficiency. Since 5-HTP is not metabolized to 5-HIAA, urinary studies could be negative unless you look for this specific molecule.

Treatment (4,6-9) is not very promising though Octreotide SQ injections can provide relief. This can be coupled with Histamine receptor blockers (H-1 blocker = diphenydramine and H-2 blocker = ranitidine). Diarrhea is treated symptomatically with anti-motility agents. Meter-dosed inhalers can help with the wheezing and associated dyspnea. There have been cases of hepatic artery embolization of the tumor in patients in which the tumor is found early and in one lobe of the liver. Surgery, hepatic artery embolization and chemotherapy have been used to reduce the tumor burden. Unfortunately, the cardiac valve abnormalities are irreversible.

Median survival once a patient develops flushing is approximately 2 1/2 years. Patients who excrete >800 micromol/day (>150 mg/d) have approximately one year survival (1).

References:

  1. Harrison's Principles of Internal Medicine, 13th edition, Ed. Isselbacher KJ, Braunwald E, Wilson JD, Martin JB, Fauci AS, Kasper DL. McGraw Hill, New York, 1994; pp. 1537-39.
  2. Kvols LK. Metastatic carcinoid tumours and the malignant carcinoid syndrome. Ann NY Acad of Sci 1994 (?): 464-470.
  3. Pellikkka PA, et al. Carcinoid heart disease: Clinical and echocardiographic spectrum in 74 patients. Circulation 1993; 87: 1188-1196.
  4. Oberg K. Chemotherapy and biotherapy in neuroendocrine tumors. Curr Opin Oncol 1993 Jan; 5(1): 110-120.
  5. Kema IP, et al. Serotonin, catecholamines, histamine and their metabolites in urine, platelets and tumor tissue of patients with carcinoid tumor. Clin Chem 1994 Jan; 40(1):86-95.
  6. Therassee E, et al. Transcatheter chemoembolization of progressive carcinoid liver metastasis. Radiology 1993 Nov; 189(2): 541-7.
  7. Ruszniewski P, et al. Hepatic arterial chemoembolization in patients with liver metastases of endocrine tumors. A prospective phase II study in 24 patients. Cancer 1993 Apr 15; 71(8): 2624-30.
  8. Debas HT, Gittes G. Somatostatin analogue therapy in functioning neuroendocrine gut tumors. Digestion 1993; 54 Suppl 1 :68-71.
  9. Hajarizadeh H., et al. Effective palliative treatment of metastatic carcinoid tumors with intra-arterial chemotherapy/chemoembolization combined with octreotide acetate. Am J. Surg 1992 May; 163(5): 479-83.

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