Carcinoid Syndrome
Carcinoid syndrome results from excessive production of vasoactive substances—most notably serotonin—by neuroendocrine tumors (carcinoid tumors). These tumors originate in the diffuse neuroendocrine system and are commonly located in the gastrointestinal tract (especially the small intestine) or the bronchopulmonary system. When they metastasize to the liver (or if they originate in the lung), the secreted substances reach the systemic circulation, causing the characteristic clinical manifestations.
Overview of carcinoid Syndrome
- Incidence: About 2 per 100,000 people per year
- Common Locations:
- GI tract (75%): often small intestine, also rectum and stomach
- Bronchopulmonary system (25%)
- Median Age at Diagnosis: ~55 years
- Pathophysiology:
- Neuroendocrine cells produce serotonin, various peptides, and other amines
- Tumors can metastasize to liver, bone, or brain
- Somatostatin and other peptide receptors are often present on the cell surface
Typical Clinical Manifestations
- Flushing
- Usually described as a dry, red-to-purple flushing of the face and upper torso
- May be precipitated by stress, alcohol, or certain foods/drugs
- Diarrhea
- Often watery and can be frequent, linked to hypermotility from serotonin and other secreted peptides
- Right-Sided Valvular Heart Disease
- Plaque-like fibrous thickening leads to tricuspid insufficiency, pulmonary valve stenosis/regurgitation
- High serotonin exposure on the right side of the heart is implicated (left side is typically unaffected unless a right-to-left cardiac shunt is present)
- Bronchoconstriction
- Less common; can manifest as wheezing
- Mediated by tachykinins and bradykinin
- Other
- Telangiectasia
- Abdominal pain, depending on tumor location and extent
- Hyperpigmentation (rare)
Note: Patients generally develop these symptoms when the tumor has metastasized to the liver (for GI primary tumors) or if the tumor is outside portal circulation (e.g., bronchopulmonary carcinoid).
Bronchopulmonary Carcinoids
- Often produce precursor molecules (e.g., 5-hydroxytryptophan) rather than serotonin
- Can secrete various polypeptide hormones (e.g., ACTH), leading to alternative clinical presentations (e.g., Cushing syndrome)
- Carcinoid syndrome is less common than with GI primaries
Diagnosis
- Clinical Suspicion
- Flushing, diarrhea, right-sided valvular problems
- Episodes of wheezing or severe diarrhea in the setting of a known or suspected tumor
- Biochemical Tests
- 24-hour urine 5-HIAA (the serotonin metabolite) is the mainstay; elevated levels confirm suspicion
- Blood levels of serotonin or chromogranin A can also help
- Tumor Localization
- Imaging
- CT or MRI of chest, abdomen to find primary or metastatic lesions
- Somatostatin receptor scintigraphy (octreotide scan) to localize tumors expressing somatostatin receptors
- PET scans with specialized tracers (e.g., 11C–5-hydroxytryptophan or 18F-fluorodeoxyglucose)
- Endoscopy (upper, lower, or bronchoscopy) depending on suspected site
- Ultrasound (e.g., rectal ultrasound) in selected cases
- Imaging
Treatment
- Surgical Resection
- Preferred for localized disease if feasible, aiming for complete removal of the tumor
- Medical Therapy
- Somatostatin Analogues (e.g., octreotide)
- Control of symptoms (flushing, diarrhea)
- Can slow tumor progression and reduce hormone secretion
- Interferon-α
- Another option to reduce tumor growth, used less frequently in modern practice
- Telotristat
- Inhibits tryptophan hydroxylase, reducing serotonin overproduction
- Systemic therapies (targeted agents, chemotherapy) in metastatic disease
- Somatostatin Analogues (e.g., octreotide)
- Locoregional Procedures
- Liver-directed therapies (e.g., hepatic artery embolization, radiofrequency ablation) for metastatic liver disease
- Can alleviate symptoms by reducing tumor burden
- Supportive Measures
- Management of carcinoid heart disease (valve replacement if severe)
- Monitoring and controlling triggers (diet, stress, etc.)
Prognosis
- Depends on tumor burden, location, and extent of metastases
- Patients with localized disease can often have good long-term outcomes
- Metastatic disease may be more indolent than typical adenocarcinomas, but can still be life-threatening if uncontrolled
Overall, early recognition, biochemical confirmation, and targeted surgical or medical intervention are key to optimizing outcomes in patients with carcinoid syndrome.