Background     The carcinoid syndrome (CS) is a symptom complex resulting from hormone secretion in patients with carcinoid tumors.  Carcinoid tumors typically grow slowly, and patients may live for many years following diagnosis.  CS becomes manifested only when sufficient concentration of hormones reaches the systemic circulation, most commonly in the presence of liver metastases.  This Fast Fact will focus on managing the symptoms of CS.

Symptoms and causes     The CS includes the complex of: flushing, diarrhea, abdominal cramping, cyanosis, bronchoconstriction, and symptoms of right heart failure. Compared with the general population and other cancer patients, CS sufferers may also be at increased risk for cognitive impairment.  Other specific symptoms depend on the hormones the tumor secretes.  Serotonin-secreting tumors cause diarrhea and abdominal cramping; bradykinin and histamine secretion lead to flushing and cyanosis. Carcinoid tumors may also produce somatostatin, norepinephrine, dopamine, gastrin, vasoactive intestinal peptide, and other hormones. Drugs that block the hormonal secretion can help to control the symptoms of carcinoid syndrome.

Diagnosis:  Usually CS is diagnosed clinically.  Supportive diagnostic tests include 24-hour urinary excretion of 5-hydroxyindoleacetic acid (5-HIAA) and tumor localization through imaging and endoscopy.

Somatostatin Analogs     These drugs are the treatment of choice for CS. Three formulations are available: short-acting octreotide (continuous infusion or 50-500 mcg TID, IV or subcutaneously); depot octreotide (standard dose is 30 mg intramuscularly every 4 weeks; however, doses up to 40 to 60 mg every 4 weeks may offer added benefit); and lanreotide (standard dosing is 30 mg every other week intramuscularly). 50-70% of patients experience a significant reduction of diarrhea and flushing episodes within seven days.  Efficacy and side effect profiles for the three preparations are similar. Side effects include pain at the injection site, abdominal bloating, fatigue, transient fever, elevated serum glucose, and asymptomatic biliary lithiasis. Annual cost varies between $25,000-$60,000, but most insurances cover it.

Interferon     Interferon alpha is effective in controlling both diarrhea and flushing, although it is inferior to the somatostatin analogs.  The dose is 3-9 mU subcutaneously three to seven times per week.  Interferon alpha therapy is often limited by its side effects: fever, anemia, thrombocytopenia, neutropenia, fatigue, depression, and flu-like symptoms.

Telotristat:  this medication is an oral tryptophan hydroxylas inhibitor.  It has been approved in the United States for the treatment of refractory diarrhea in adults with CS that is inadequately controlled by somatostatin therapy alone.  The recommended dose is 250 mg three times a day with food.  Nausea and depression are common side effects at higher doses.  Annual cost averages around $90,000 but most insurances will cover it.

Other symptom-specific treatments

• Diarrhea:  Besides somatostatin analogs, interferon, and telostristat, cyproheptadine is an alternative treatment for carcinoid-associated diarrhea.  60% of patients report improvement within one week.  The dosage is 4 mg TID given orally as a tablet; it can be titrated up to 0.5 mg/kg per day.  Side effects include sedation, dry mouth, dizziness, mild blurring of vision, nausea, and vomiting.  Loperamide and opioids are non-specific anti-diarrheal agents that can be used for mild symptoms.
• Wheezing: bronchodilators.
• Heart failure: diuretics; tricuspid valve replacement.

Non-Drug Treatments     Patients should be counseled to identify and eliminate stressors that reproducibly cause symptoms—this may include specific stressful situations, foods, or alcohol.

Other     Other treatments for refractory symptoms include systemic chemotherapy, hepatic artery embolization, hepatic chemoembolization, or debulking surgery of hepatic metastases. Radiolabeled somatostatin analog 177-Lutetium Dotatate can be used for patients with somatostatin receptor expressing tumors. (13)