What is the next step for a patient with episodic diarrhea, urticaria, flushing, nausea, and vomiting, and elevated chromogranin levels, suggestive of a carcinoid tumor?

Diagnostic Approach for a Patient with Suspected Carcinoid Syndrome

The next step for a 53-year-old male with episodic diarrhea, urticaria, flushing, nausea, vomiting, and elevated chromogranin A should be multiphasic CT or MRI imaging of the abdomen and pelvis to localize the suspected neuroendocrine tumor, followed by somatostatin receptor scintigraphy (Octreoscan). 1, 2

Diagnostic Evaluation Algorithm

Initial Assessment of Chromogranin A Elevation

• Chromogranin A is the best general serum marker for neuroendocrine tumors, with elevated levels in 60% or more of patients with both functioning and non-functioning neuroendocrine tumors 2
• Before proceeding with advanced imaging, rule out false positives by confirming the patient is not taking proton pump inhibitors (discontinue for at least 1 week before retesting), and does not have renal failure, liver failure, hypertension, or chronic gastritis 1, 2
• Elevated levels twice the normal limit or higher correlate with tumor volume and are associated with shorter survival times (HR, 2.8; 95% CI, 1.9–4.0; P<.001) 2

Imaging Studies

• Multiphasic CT/MRI scan of the abdomen and pelvis should be performed to localize the tumor and confirm the diagnosis 1
• Somatostatin receptor scintigraphy (Octreoscan) should follow, as it can detect tumors that may be missed by other diagnostic studies 1, 3
  • This imaging has higher sensitivity (82.9%), specificity (97.7%), and accuracy (88.0%) than chromogranin A alone (62.2%, 83.7%, and 69.6%, respectively) for detecting neuroendocrine tumors 3

Additional Biochemical Testing

• Measure 24-hour urinary 5-hydroxyindoleacetic acid (5-HIAA), a metabolite of serotonin, particularly useful for serotonin-producing carcinoids 1, 2
  • Patient should avoid certain foods (avocados, bananas, cantaloupe, eggplant, pineapples, plums, tomatoes, hickory nuts, plantain, kiwi, dates, grapefruit, honeydew, walnuts) for 48 hours before collection 1
  • Patient should also avoid coffee, alcohol, smoking, and medications that can increase 5-HIAA (acetaminophen, ephedrine, diazepam, nicotine, glyceryl guaiacolate, phenobarbital) 1
• Consider measuring chromogranin B, which may be elevated when chromogranin A is in the reference range 2, 4

Management Considerations

Prevention of Carcinoid Crisis

• If invasive procedures (biopsy, surgery) are planned, recognize the risk of carcinoid crisis, which can cause bronchospasm, hypotension, arrhythmias, and cardiopulmonary failure 1
• Prophylactic administration of octreotide acetate can prevent, abort, or treat carcinoid crisis 1, 5

Treatment Options

• If carcinoid tumor is confirmed, octreotide acetate injection is indicated for treatment of severe diarrhea and flushing episodes associated with metastatic carcinoid tumors 5
• The recommended daily dosage during the first 2 weeks of therapy ranges from 100 to 600 mcg/day in 2-4 divided doses given subcutaneously 5
• The median daily maintenance dosage is approximately 450 mcg, but clinical benefits can be obtained with as little as 50 mcg, while others require up to 1500 mcg/day 5

Important Caveats

• Combining chromogranin A testing with somatostatin receptor scintigraphy increases sensitivity (92.7%) but decreases specificity (81.4%) for tumor detection 3
• Rising chromogranin A levels in an asymptomatic patient with stable imaging does not necessarily indicate the need for new therapy 1, 2
• Some adenocarcinomas may show neuroendocrine differentiation and cause elevated chromogranin A levels, requiring careful histopathological evaluation 6, 7