Carcinoid syndrome is a paraneoplastic syndrome caused by bioactive compounds released from neuroendocrine tumors (NETs), most commonly arising from the small intestine. It occurs in approximately 10% of patients with NETs.

Key Points

• Caused by secretion of serotonin and other vasoactive substances
• Most common in metastatic midgut NETs
• Classic triad: flushing, diarrhea, and right-sided heart disease
• Diagnosis requires biochemical and imaging studies
• Treatment involves both symptom control and tumor management

Cardinal Manifestations

Cutaneous (85%)

• Flushing patterns:
  • Foregut: prolonged red/purple flush
  • Midgut: brief pink/red flush
  • Triggered by stress, alcohol, exercise
• Telangiectasias
• Pellagra (niacin deficiency)

Gastrointestinal (80%)

• Secretory diarrhea
  • Watery, non-bloody
  • Often postprandial
  • Can be severe (>20 stools/day)
• Abdominal cramping
• Malabsorption
• Weight loss

Cardiovascular

• Carcinoid heart disease (50%)
  • Right-sided valve disease
  • Tricuspid regurgitation
  • Pulmonary valve stenosis
• Hemodynamic changes
  • Hypotension
  • Tachycardia

Respiratory (15%)

• Wheezing
• Bronchospasm
• Dyspnea

Diagnostic Approach

Biochemical Testing

• 24-hour urinary 5-HIAA
  • Sensitivity: 90%
  • Specificity: 90%
  • Dietary restrictions required
• Serum markers
  • Chromogranin A
  • Neuron-specific enolase
  • Serotonin

Imaging Studies

• Anatomical imaging
  • CT/MRI abdomen/pelvis
  • Chest imaging
  • Cardiac MRI/ECHO
• Functional imaging
  • Somatostatin receptor scintigraphy
  • 68Ga-DOTATATE PET
  • FDG-PET (high-grade tumors)

Other Assessments

• Endoscopy
• Echocardiography
• NT-proBNP levels
• Histopathological confirmation

Treatment Strategy

Symptom Control

• Somatostatin analogs
  • Octreotide (100-500 μg SC tid)
  • Lanreotide (60-120 mg monthly)
  • Long-acting formulations
• Anti-diarrheal agents
  • Loperamide
  • Diphenoxylate/atropine
  • Cholestyramine
• Other medications
  • H1/H2 blockers
  • Telotristat ethyl
  • Cyproheptadine

Tumor-Directed Therapy

• Surgery
  • Primary tumor resection
  • Metastasectomy
  • Debulking procedures
• Liver-directed therapy
  • Embolization
  • Radioembolization
  • Ablation
• Systemic therapy
  • Peptide receptor radionuclide therapy
  • Everolimus
  • Interferon-alpha

Major Complications

Carcinoid Crisis

• Triggers
  • Anesthesia
  • Surgery
  • Chemotherapy
  • Tumor manipulation
• Clinical features
  • Severe flushing
  • Bronchospasm
  • Hemodynamic instability
  • Cardiac arrhythmias
• Management
  • Prophylactic octreotide
  • IV fluids
  • Vasopressors if needed
  • H1/H2 blockers

Carcinoid Heart Disease

• Pathophysiology
  • Fibrotic plaques
  • Valve dysfunction
  • Right heart failure
• Management
  • Regular cardiac monitoring
  • Diuretics
  • Valve replacement if needed

Follow-up Care

Surveillance Schedule

• Biochemical monitoring
  • 24-hour urinary 5-HIAA every 3-6 months
  • Chromogranin A levels
  • NT-proBNP monitoring
• Imaging
  • Cross-sectional imaging every 3-6 months
  • Annual echocardiogram
  • Nuclear imaging as needed

Prognostic Factors

• Favorable
  • Early diagnosis
  • Well-differentiated tumors
  • Absence of carcinoid heart disease
  • Good performance status
• Poor
  • High tumor burden
  • Carcinoid heart disease
  • High chromogranin A levels
  • High urinary 5-HIAA levels

Quality of Life Considerations

• Dietary modifications
• Stress management
• Support groups
• Regular exercise as tolerated
• Psychological support