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A 40-year-old man comes to the emergency department because of a 3-week history of episodic cutaneous flushing, diarrhea, and wheezing. He has a past medical history of hypertension and type 2 diabetes mellitus. His temperature is 36.6°C (97.9°F), pulse is 125/min, respirations are 30/min, and blood pressure is 90/60 mm Hg. Pulmonary examination shows diffuse wheezes in both lung fields. Cardiac examination shows a prominent "v" wave of the jugular vein and a 1/6 holosystolic murmur best heard on the left lower sternal border. Abdominal examination shows hyperactive bowel sounds. Which other clinical findings is likely to be present?
Contributors:Sam Gillespie, BSc, Sarah Clifford, BMBS, BSc (Hons), Alaina Mueller, Amanda J. Grieco, PhD
Carcinoid syndrome refers to a constellation of symptoms like diarrhea, shortness of breath and flushing, which arise when a specific type of tumor called a neuroendocrine tumor begins secreting hormones.
Neuroendocrine cells are found in tissues throughout the body, particularly in the epithelial layer of gastrointestinal organs and the lungs. They receive signals from nerve cells and, in response, they release hormones into the blood.
Neuroendocrine cells release a variety of hormones including amines, like serotonin and histamine; polypeptides, like bradykinin, a vasodilator; and prostaglandins which are also powerful vasodilators. The production of these hormones can also be regulated by other hormones.
For example, somatostatin is a hormone that’s made by cells in the hypothalamus as well as the gastrointestinal tract, and it travels through the blood and binds to receptors on the surface of neuroendocrine cells.
Binding of somatostatin inhibits the release of a number of hormones from neuroendocrine cells, including serotonin.
Now, when serotonin does get released from neuroendocrine cells, it enters the liver through the portal vein.
The remaining serotonin is not metabolized, and this portion remains in the systemic circulation where it has various effects.
In the gastrointestinal tract, serotonin increases motility and peristalsis; in the vasculature, platelets take up the serotonin and later use it to constrict blood vessels, particularly after injury; and in the connective tissue of the heart, it stimulates fibroblasts which make lots of collagen.
A cell can become cancerous when DNA mutations cause abnormal cellular functions, like uncontrolled, unregulated cellular divisions forming a tumor.
The limitless replication means the developing tumor can invade nearby tissue and spread, through the blood and lymph to distant sites in the body, called metastasis.
If a neuroendocrine cell mutates and transforms into a cancerous cell, then that cell can continue dividing until it becomes a little mass which is a neuroendocrine tumor. And most of the time these neuroendocrine tumors develop in the gastrointestinal tract.
Some of the abnormal functions of the cancerous neuroendocrine cells include producing and secreting large amounts of hormones; and, counterintuitively, they also express more somatostatin receptors on their surface, particularly in the gastrointestinal tract - although it’s unclear why that happens.
Neuroendocrine tumors tend to be slow growing, although some can metastasize, often depending on the location.
The most common site for a neuroendocrine tumor to metastasize to is the liver. So the liver can really be a primary or secondary site of disease.
And it turns out that metastasis, especially to the liver, is often necessary for carcinoid syndrome to occur.
That’s because it leads to liver dysfunction which decreases the liver’s ability to metabolize the hormones which get released from the neuroendocrine cells, allowing them to build up and cause symptoms.
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