Carcinoid syndrome

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Introduction0:00–0:23

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 tumors were also called “carcinoid tumors” in the past, because of their association with carcinoid syndrome.

Physiology0:23–2:04

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.
In the liver, some of the serotonin is metabolized to 5-hydroxyindoleacetic acid which is eliminated from the body through the urine.
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.

Pathology2:04–4:48

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. Common primary sites for neuroendocrine tumors, are someplace along the small or large intestines, as well as the stomach, pancreas, and liver, the lungs, the ovaries in females, and the thymus.
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.
Increased histamine and bradykinin can cause vasodilation leading to flushing, while histamine can also cause itching. Increased serotonin can cause thickening of the collagen, called fibrosis, in the heart valves leading to heart dysfunction.
Most often, fibrosis affects the right side of the heart, causing tricuspid regurgitation and pulmonary stenosis; and bronchoconstriction leading to asthma, shortness of breath, and wheezing.
Fibrosis can also affect the abdominal mesenteries, as well as the retroperitoneal area. In the latter situation, extensive fibrosis may cause ureteral obstruction and impair kidney function.The increased synthesis of serotonin also reduces the amount of tryptophan available to the body to make niacin, vitamin B3.
Reduced levels of niacin can cause pellagra, a disease which causes symptoms like inflamed skin and mental confusion. The most common symptoms of carcinoid syndrome include diarrhea; shortness of breath, and flushing and itching.

Symptoms4:48–5:04

These symptoms can be worsened by alcohol or emotional stress since these can further stimulate the neuroendocrine cells.To diagnose carcinoid syndrome, a urinalysis can be done, which usually shows increased levels of 5-hydroxyindoleacetic acid, while blood tests can show a niacin deficiency.

Diagnosis5:04–6:02

Identifying the primary neuroendocrine tumor can be done through medical imaging techniques like a CT or MRI scan, or through techniques that identify the number of cells that express somatostatin receptors, like the Octreoscan, or the Gallium 68 PET scan.
With an Octreoscan, a radiolabeled somatostatin analogue, octreotide, is injected, and it binds to the increased number of somatostatin receptors on tumor cells.
A gamma camera is then used to pick up the radioactive octreotide signals, and translates them into an image that shows where the tumor is.
Another diagnostic imaging technique, called a Gallium 68 PET scan, uses the same principle, and it seems to be more accurate at detecting neuroendocrine tumors.Treatment of carcinoid syndrome is aimed at stopping hormone production from the neuroendocrine cells.

Treatment6:02–6:29

This can be done with somatostatin analogues, which bind to the somatostatin receptor and inhibit hormone release. Decreasing emotional stress and alcohol consumption can also help limit hormone release.
Treatment of the primary tumor is usually done through surgical resection.All right, as a quick recap, carcinoid syndrome is a set of symptoms that occur when a neuroendocrine tumor secretes excess serotonin, histamine, and bradykinin.

Review6:29–6:54

The classic symptoms include diarrhea; shortness of breath, and flushing and itching. Diagnosis can be made with an octreotide scan, as well as elevated 5-hydroxyindoleacetic acid in the urine, and decreased niacin levels in the blood.