What is Carcinoid Syndrome?

Carcinoid Syndrome is a collection of symptoms caused by hormones (primarily serotonin and other vasoactive substances) released by carcinoid tumors—a type of neuroendocrine tumor (NET). The syndrome occurs when these hormones reach the systemic circulation, typically when the tumor has metastasized to the liver or when the primary tumor is outside the GI tract.

What are Carcinoid Tumors?

• Neuroendocrine Tumors (NETs): Slow-growing tumors arising from neuroendocrine cells
• Most Common Locations:
  • Small intestine (ileum—most common site for carcinoid syndrome)
  • Appendix (usually benign, rarely causes syndrome)
  • Colon, rectum
  • Lungs, bronchi
  • Pancreas, stomach (rare)
• Many are found incidentally and never cause symptoms

Why Doesn't Every Carcinoid Tumor Cause Carcinoid Syndrome?

• GI Carcinoids WITHOUT Liver Mets: Hormones drain into portal vein → liver metabolizes them before reaching systemic circulation → no syndrome
• WITH Liver Metastases: Tumor in liver releases hormones directly into systemic circulation → syndrome develops
• Non-GI Primary (Lungs, Ovaries): Hormones bypass liver → can cause syndrome even without mets
• Only ~10% of carcinoid tumors cause carcinoid syndrome

Classic Symptoms ("The Carcinoid Triad"):

1. Flushing:

• Sudden redness of face, neck, upper chest
• Warmth, sometimes sweating
• Lasts seconds to minutes
• Triggered by alcohol, stress, certain foods, emotions
• Most common symptom (85-90%)

2. Diarrhea:

• Watery, secretory diarrhea
• Multiple bowel movements per day
• Can lead to dehydration, electrolyte imbalances
• Occurs in ~70-80% of patients

3. Wheezing/Bronchospasm:

• Asthma-like symptoms
• Shortness of breath
• Occurs in ~10-20%

Other Symptoms:

• Abdominal Pain, Cramping
• Weight Loss
• Pellagra-Like Skin Changes: Rough, scaly skin (from niacin deficiency—tumor uses tryptophan to make serotonin instead of niacin)
• Carcinoid Heart Disease: Fibrosis of right-sided heart valves (tricuspid, pulmonary) → heart failure (seen in ~50% of patients with long-standing syndrome)

Carcinoid Crisis (Medical Emergency):

• Severe, Life-Threatening Episodes: Extreme flushing, hypotension (dangerously low BP), bronchospasm, tachycardia, confusion
• Triggers: Surgery, anesthesia, tumor manipulation, stress
• Treatment: IV octreotide, fluid resuscitation, ICU care

Diagnosis:

1. 24-Hour Urine 5-HIAA (5-Hydroxyindoleacetic Acid):

• Gold Standard Test
• 5-HIAA is a breakdown product of serotonin
• Elevated in carcinoid syndrome (>25 mg/24 hours highly suggestive)
• Dietary Restrictions: Avoid serotonin-rich foods 3 days before test (bananas, avocados, pineapple, walnuts, kiwi)
• False Positives: Certain medications (SSRIs, acetaminophen, caffeine)

2. Chromogranin A (CgA):

• Tumor marker for neuroendocrine tumors
• Elevated in most NETs
• Useful for monitoring disease progression/response to treatment
• Not specific (can be elevated in other conditions, PPIs)

3. Imaging (Localize Tumor and Metastases):

• CT or MRI Abdomen/Pelvis: Identify primary tumor, liver mets
• Octreotide Scan (Somatostatin Receptor Scintigraphy): Functional imaging; carcinoid tumors have somatostatin receptors → take up radiotracer → "lights up" on scan
• Gallium-68 DOTATATE PET/CT: Newer, more sensitive functional imaging
• Echocardiogram: Assess for carcinoid heart disease

Treatment:

1. Somatostatin Analogs (SSAs) - FIRST-LINE for Symptom Control:

• Octreotide (Sandostatin®):
  • Short-acting: 100-600 mcg subcutaneous 2-3x/day
  • Long-acting (Sandostatin LAR®): 20-30 mg IM monthly
• Lanreotide (Somatuline®): 120 mg subcutaneous monthly
• Mechanism: Inhibit hormone release from tumor; also slow tumor growth
• Effects: Control flushing, diarrhea in 70-90%; reduce tumor progression
• Side Effects: GI symptoms (nausea, cramping), gallstones (20-50% develop—prophylactic cholecystectomy during surgery sometimes done)

2. Surgery (Curative if Resectable):

• Resect primary tumor ± liver metastases if localized
• Debulking surgery (cytoreduction) even if not curative—reduces hormone production
• Preoperative Octreotide: Prevent carcinoid crisis during surgery

3. Liver-Directed Therapies (If Liver Mets):

• Hepatic Artery Embolization or Chemoembolization: Block blood supply to liver tumors
• Radiofrequency Ablation (RFA): Destroy tumors with heat
• Liver Transplant: Very rare; for select patients with liver-only disease

4. Peptide Receptor Radionuclide Therapy (PRRT):

• Lutetium-177 DOTATATE (Lutathera®): Radioactive drug that binds to somatostatin receptors on tumor cells → delivers targeted radiation
• For advanced, progressive NETs
• Significantly prolongs progression-free survival

5. Chemotherapy:

• Generally less effective for carcinoid tumors (more effective for high-grade NETs or pancreatic NETs)
• Streptozocin, 5-FU, temozolomide, capecitabine

6. Targeted Therapy (mTOR Inhibitor):

• Everolimus (Afinitor®): Slows tumor growth in advanced NETs

7. Symptomatic Treatment:

• Diarrhea: Loperamide, diphenoxylate-atropine
• Niacin Supplementation: Prevent pellagra
• Diuretics: For carcinoid heart disease

Monitoring:

• Symptoms: Flushing, diarrhea frequency
• 24-Hour Urine 5-HIAA, Chromogranin A: Every 3-6 months
• Imaging (CT/MRI): Every 3-12 months (depends on tumor grade/behavior)
• Echocardiogram: Annually or as needed (screen for carcinoid heart disease)

Prognosis:

• Carcinoid tumors are generally slow-growing
• 5-Year Survival:
  • Localized (no mets): >95%
  • Regional spread: ~70-80%
  • Distant metastases: ~50-70%
• Many patients live for years even with metastatic disease with good symptom control
• Carcinoid heart disease is a major cause of morbidity/mortality