From the Guidelines
Paraneoplastic carcinoid syndrome is a condition where a carcinoid tumor, typically in the gastrointestinal tract or lungs, secretes bioactive substances that cause symptoms distant from the primary tumor site, such as flushing, diarrhea, and bronchospasm, and is usually observed in patients with liver metastases or retroperitoneal disease. This condition is characterized by the secretion of various hormones and vasoactive peptides, including serotonin, histamine, and tachykinins, into the systemic circulation, causing episodic symptoms 1. The prognosis for patients with carcinoid tumors varies according to stage at diagnosis, histologic classification, and primary tumor site, with approximately 50% to 66% of patients with carcinoid syndrome developing valvular cardiac complications 1.
Diagnosis and Treatment
The diagnosis of paraneoplastic carcinoid syndrome involves identifying the underlying carcinoid tumor and managing the paraneoplastic symptoms. First-line therapy includes surgical resection of the primary tumor when possible, and somatostatin analogs like octreotide are the mainstay of treatment for symptom management 1. These medications block the release of bioactive substances causing symptoms, and additional medications may include telotristat ethyl for persistent diarrhea, antihistamines for flushing, and bronchodilators for wheezing.
Management of Symptoms
In cases of carcinoid heart disease, cardiac monitoring and management are essential. The effectiveness of these treatments stems from their ability to inhibit hormone secretion from the tumor cells, thereby reducing the systemic effects that characterize paraneoplastic carcinoid syndrome. Somatostatin analogs are the first-line treatment of carcinoid syndrome and may be considered as first-line systemic antiproliferative treatment in unresectable PCs, particularly of low-grade TC and AC 1. Locoregional or radiotargeted therapies should be considered for metastatic disease, and systemic chemotherapy is used for progressive PCs, although cytotoxic regimens have demonstrated limited effects.
Key Considerations
- Approximately one-third of carcinoid tumors arise in the lungs or thymus, and two-thirds arise in the gastrointestinal tract 1
- The classic syndrome is not usually observed unless liver metastases or, rarely, retroperitoneal disease have occurred 1
- Somatostatin receptor imaging may visualize nearly 80% of the primary tumors and is most sensitive for metastatic disease 1
- Plasma chromogranin A can be increased in PCs 1
From the Research
Definition and Causes
- Paraneoplastic carcinoid syndrome is a condition caused by the release of serotonin and other substances from well-differentiated neuroendocrine tumors (NETs) 2.
- Carcinoid tumors are rare and usually slow-growing, but some patients with advanced metastatic disease can develop symptoms of carcinoid syndrome, which results in debilitating diarrhea and flushing 3.
- The symptoms of carcinoid syndrome are thought to be related to the ability of the tumors to produce serotonin 3.
Symptoms
- The hallmark symptoms of carcinoid syndrome are flushing and diarrhea 2.
- Atypical signs and symptoms can include wheezing, abdominal pain, valvular heart disease, telangiectasias, pellagra, and the complications of mesenteric fibrosis, including ureteral obstruction, bowel obstruction, and bowel ischemia 2.
- The classic "carcinoid triad" associated with the syndrome includes flushing, diarrhea, and cardiac involvement 4.
Diagnosis and Treatment
- The diagnosis of carcinoid syndrome requires symptoms and corresponding elevations in lab tests 2.
- Treatment options include surgery and medical management with somatostatin analogs 2.
- Somatostatin analogs such as octreotide and lanreotide can control many of the carcinoid symptoms 5, 4.
- Other treatment options include hepatic resection, hepatic artery chemoembolization, and radionuclide therapy 6, 5.