Signs and symptoms
Pathophysiology
The carcinoid syndrome occurs secondary to neuroendocrine tumors. These tumors occur mostly in the gut and less commonly in the lungs, but may also occur in other places in the body such as the pancreas, kidneys, and other organs. Neuroendocrine tumors produce several biologically active substances, mainly amines and peptides. There are over 40 substances known to be secreted by these tumors but the exact effect of each and their contribution to the carcinoid syndrome is unknown. The most common substances found to be released and contribute to the syndrome include serotonin, histamine, tachykinins, kallikrein, and prostaglandins with the greatest contribution appearing to be from serotonin. The symptoms of the carcinoid syndrome result from the action of these substances largely on the blood vessels. These biologic substances are often metabolized and inactivated by the liver in a process known as first pass metabolism. This is why carcinoid syndrome most often occurs in patients whom the neuroendocrine tumor has metastasized to the liver, which allows the substances to bypass the first pass metabolism. Neuroendocrine tumors arising in the bronchi may be associated with manifestations of carcinoid syndrome without liver metastases because their biologically active products reach the systemic circulation before passing through the liver and being metabolized.Carcinoid crisis
Carcinoid crisis is an extreme exacerbation of the carcinoid syndrome. This results from excessive release of amines by the neuroendocrine tumors. It is largely a result of stressful procedures such as anesthesia, surgery, or radiation treatment. Symptoms of carcinoid crisis include flushing, hypotension, arrhythmia and bronchospasm.Carcinoid heart disease
Carcinoid heart disease is the result of valvular damage related to the vasoactive substances released by the neuroendocrine tumor reaching the right side of the heart. This mainly affects the right side of the heart unless there is anomalous circulation (i.e. patent foramen ovale) because the lungs will metabolize the substances released by the tumor similar to how the liver will. After initial tissue injury around the valves, plaque will develop and fibrosis will occur, possibly mediated by excess serotonin.Diagnosis
With a certain degree of clinical suspicion, the most useful initial test is the 24-hourImaging
Imaging studies should be largely focused on the abdomen and pelvis because the neuroendocrine tumors causing the carcinoid syndrome largely arise in the gut. Nuclear medicine gamma camera imaging that utilizes radioactive somatostatin analogues such as indium-111 pentetreotide are used to localize the tumor. PET scan can also be used to find the primary tumor site. Bronchoscopy with biopsy can performed if there is evidence of a pulmonary tumor. For patients with serotonin elevated 5x the upper limit of normal or more, an echocardiogram is recommended for evaluation of carcinoid heart disease.Differential diagnosis
Other conditions similar to the carcinoid syndrome that should be considered include: *Treatment
Treatment of the carcinoid syndrome is focused on controlling the proliferation of the primary tumor and symptomatic control of the symptoms with somatostatin analogues octreotide or lanreotide. These analogues can help control the growth of the tumor itself and the associated symptoms of the carcinoid syndrome. In patients whose symptoms are refractory to initial doses, increasing the dose or switching to another analogue pasireotide may be effective. In patients who continue to be refractory, mTOR inhibitors such as everolimus. The TPH inhibitor telotristat ethyl may be useful in controlling diarrhea associated with the carcinoid syndrome. Peptide directed radiotherapy (PRRT) is another alternative treatment for patients who failed somatostain analogue therapy. This method uses radioactive somatostatin analogues such as 177Lu-Dotatate or 90Y-Edotreotide to target tumors directly. These therapies are effective for metastatic disease but studies have been limited to about 6-month time periods. Cytoreductive surgery performed chemically with 131 metaiodobenzylguanidine (131I-MIBG) may also control symptoms starting around 6–15 months post procedure and lasting as long as 39 months. There are also procedures that target the liver directly such as radiofrequency ablation or radioembolization that deliver targeted therapy directly to the liver through special catheters. This is especially useful for patients with liver metastases.Carcinoid heart disease
The most important aspect of treating carcinoid heart disease is detecting its presence with echocardiography, likely with color doppler. Treatment consists of the same treatment as patients with heart failure with definitive treatment being surgical valve repair or replacement.Uncertainties
Disease progression is difficult to ascertain because the disease canEpidemiology
The incidence of neuroendocrine tumors in the US lies somewhere from 2.7 to 4.3 per 100,000 people and appears to be increasing over time. The incidence of the carcinoid syndrome is about 0.27 per 100,000 people in the US, about 10% of all people with neuroendocrine tumors. There does not appear to be any variance by gender however patients of African American ethnicity appear to be affected by the carcinoid syndrome more often.Nonhuman animals
The carcinoid syndrome can affect other animals similarly to humans. Similarly to humans, the carcinoid syndrome is due to neuroendocrine tumors that arise mainly from the bowel but also from other organs. Common signs in animals include vomiting, diarrhea, and weight loss but other symptoms that are more common in humans such as flushing, hypotension and diarrhea can also occur. Similar to humans, the cause of the carcinoid syndrome is the release of bioactive substances such as serotonin and histamine.See also
* Carcinoid * Neuroendocrine tumor * Small intestine neuroendocrine tumor * Kulchitsky cells * ApudomaReferences
Further reading
* * * *External links
{{DEFAULTSORT:Carcinoid Syndrome Paraneoplastic syndromes Syndromes affecting the gastrointestinal tract