Carcinoid Syndrome – causes, symptoms, diagnosis, treatment, pathology

Carcinoid Syndrome – causes, symptoms, diagnosis, treatment, pathology


Carcinoid, refers to a specific type of tumor,
a carcinoid tumor, which causes neuroendocrine cells to secrete hormones, which lead to all
sorts of symptoms like diarrhea, shortness of breath and flushing. So when these symptoms develop as a result
of a carcinoid tumor, it’s called carcinoid syndrome. 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 bind 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. 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 carcinoid tumor. And most of the time these carcinoid 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. Carcinoid tumors tend to be slow growing,
although some can metastasize, often depending on the location. Common primary sites for carcinoid 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, fibrosis, particularly in the heart valves leading to heart dysfunction,
like tricuspid regurgitation and pulmonary stenosis; and bronchoconstriction leading
to asthma, shortness of breath, and wheezing.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. These symptoms can be worsened by alcohol
or emotional stress since these can further stimulate the neuroendocrine cells. Diagnosis of carcinoid syndrome can be made
through medical imagining like a CT scan. An octreoscan can help identify carcinoid
tumors by using an injected radiolabeled somatostatin analogue, octreotide, to bind to the increased
number of somatostatin receptors on tumor cells. Urinalysis will show increased levels of 5-hydroxyindoleacetic
acid, while blood tests can show a niacin deficiency. Treatment of carcinoid syndrome is aimed at
stopping hormone production from the neuroendocrine cells. 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 carcinoid tumor itself with
surgical resection or chemotherapy can also alleviate carcinoid syndrome. So, to recap: carcinoid syndrome is a set
of symptoms that occur as a result of the overproduction of serotonin, histamine, and
bradykinin by neuroendocrine cells which develop into a carcinoid tumor. 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.

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