From the Guidelines
Carcinoid syndrome typically starts when a carcinoid tumor, usually in the small intestine, appendix, or lungs, begins secreting excessive amounts of hormones like serotonin into the bloodstream, usually after metastasizing to the liver. The syndrome usually doesn't develop until the tumor has metastasized to the liver, as hormones released by tumors in other locations are typically metabolized by the liver before reaching the systemic circulation 1. Common initial symptoms include facial flushing (often triggered by alcohol, spicy foods, or stress), diarrhea, abdominal cramping, wheezing, and heart valve damage over time.
Key Points
- The prognosis for patients with carcinoid tumors varies according to stage at diagnosis, histologic classification, and primary tumor site 1.
- Approximately 50% to 66% of patients with carcinoid syndrome develop valvular cardiac complications consisting of tricuspid regurgitation and/or pulmonary stenosis 1.
- Diagnosis involves measuring 5-HIAA (a serotonin metabolite) in 24-hour urine collection, blood tests for chromogranin A, and imaging studies like CT scans or octreotide scans to locate tumors.
- Treatment focuses on controlling the tumor through surgery when possible and managing symptoms with medications like somatostatin analogs (octreotide, lanreotide), which block hormone release, and specific treatments for symptoms such as antidiarrheals for bowel issues 1.
Symptoms and Diagnosis
- Carcinoid syndrome occurs in approximately 20% of cases of well-differentiated endocrine tumours of the jejunum or ileum (midgut NET) and consists of dry flushing (without sweating; 70% of cases) with or without palpitations, diarrhoea (50% of cases) and intermittent abdominal pain (40% of cases) 1.
- The syndrome develops gradually, and early recognition is important for effective management and preventing complications like carcinoid heart disease.
From the FDA Drug Label
Serotonin plays a role in mediating secretion, motility, inflammation, and sensation of the gastrointestinal tract, and is over-produced in patients with carcinoid syndrome. The start of carcinoid syndrome is not explicitly stated in the provided drug label.
- The label discusses the role of serotonin in carcinoid syndrome and how the drug telotristat ethyl reduces serotonin production, but it does not provide information on when or how carcinoid syndrome begins 2.
From the Research
Carcinoid Syndrome Onset
The onset of carcinoid syndrome is often associated with the secretion of bioactive substances by neuroendocrine tumors, particularly in the presence of liver metastases 3. The most typical clinical manifestations of carcinoid syndrome include:
- Cutaneous flushing
- Diarrhea These symptoms can significantly affect a patient's quality of life, increase costs, and result in changes to their lifestyle, such as diet, work, physical activity, and social life 4.
Pathophysiology and Diagnosis
The pathophysiology of carcinoid syndrome involves the secretion of several humoral factors, including:
- Serotonin (5-HT)
- Histamine
- Kallikrein
- Prostaglandins
- Tachykinins The diagnosis of carcinoid syndrome can be verified through various methods, including:
- Serum chromogranin A as a nonspecific biochemical tumor marker
- Increased urinary excretion of 5-hydroxy indole acetic acid (5-HIAA) as a specific marker for the carcinoid syndrome 3
- Imaging studies such as transabdominal ultrasonography, endoscopy, and computerized tomography 3
Treatment and Management
The treatment of carcinoid syndrome typically involves a multidisciplinary approach, with somatostatin analogues as the first-line treatment 4. However, new therapeutic interventions are needed to address the inevitable clinical progression of the disease. Available treatment options include: