colloid syndrome. E34.0 Carcinoid syndrome. Carcinoid Syndrome: What is it?

There is a certain type of neuroendocrine tumors - carcinoids, which release certain hormones into the blood (most often these are serotonin, prostaglandin, histamine and others). Due to the entry of these hormones into the blood, a person develops a carcinoid syndrome, which is characterized by certain symptoms.

It turns out that the root cause of the development of such a pathological condition is a tumor in any of the organs. In this case, a hormone-producing tumor can be located:

in the appendix;
in the small or large intestine;
in the stomach.

The reasons

As is already clear from the definition of pathology, the causes of the development of carcinoid syndrome are the presence of a neuroendocrine tumor in the patient's body. Fortunately, these tumors grow very slowly, therefore, if the pathology is detected at an early stage, a complete cure or prolongation of a person's life by 10 years or more is possible. That is why it is so important to have regular check-ups and pay attention to any suspicious symptoms that may indicate carcinoid syndrome - a sign of cancer in the body.

Predisposing factors for the development of this pathological condition may be:

hereditary predisposition (in particular, multiple endocrine neoplasias);
gender - pathology is more often observed in men;
excessive drinking and smoking;
certain types;
history of stomach disease.

In addition, different forms of carcinomas occur in people of different races. Thus, African Americans are more likely to experience stomach tumors, while Europeans have lung carcinomas.

Symptoms

With tumors of various localization, the symptoms of carcinoid syndrome appear with a certain degree of probability. For example, tumors of the small intestine of all neuroendocrine tumors occur in 10% of cases. In this case, the signs of carcinoid syndrome in such an oncological disease will be as follows:

diarrhea;
paroxysmal abdominal pain;
nausea and vomiting.

Tumors of the appendix are even rarer, and often the prognosis for removing the appendix is favorable in cases where the tumor is small and does not metastasize.

The most common neuroendocrine carcinoma is gastric, which is of three types and has a high probability of metastasis:

Type I is a tumor less than 1 cm in size. It is often benign, so the prognosis in the treatment of pathology is favorable;
Type II - a neoplasm up to 2 cm in size, which rarely degenerates into a malignant tumor;
Type III is the most common - these are tumors up to 3 cm in size, which are malignant and often grow into surrounding tissues. The prognosis, even with timely diagnosis, is poor. But, if a tumor is detected at an early stage during a preventive examination and treated comprehensively, then it is possible to provide a person with 10–15 years of a full life, which is already a lot, taking into account a difficult diagnosis.

In other places of localization of neoplasms, the carcinoid syndrome develops almost immediately after the onset of the tumor, so a timely visit to a doctor and treatment of the underlying pathology can save a person's life. If we talk about the symptoms of carcinoid syndrome, they are typical, but they are not diagnostically important, since individually they can manifest themselves in many other pathologies of the internal organs.

So, the main symptoms of a condition such as carcinoid syndrome are:

diarrhea;
hyperemia;
abdominal pain;
wheezing;
pathology of the cardiovascular system;
tides.

In addition, some people may develop a carcinoid crisis, a life-threatening condition with severe consequences.

Diarrhea occurs in most patients with carcinoid syndrome. It occurs for two reasons - either due to the effect of the hormone serotonin, or due to the location of the tumor in the intestine. Hyperemia in a condition such as carcinoid syndrome is characteristic. A person's face turns red in the cheeks and neck, the body temperature rises, dizziness appears and the heartbeat quickens, although blood pressure is within the normal range.

Other symptoms such as abdominal pain, wheezing in the lungs, and swelling of the extremities or accumulation of fluid in the abdominal cavity (which occurs with pathologies of the heart) are not characteristic - they can occur with any disease, so they are not of diagnostic value. But hot flashes, similar to those that women experience with, can characterize the carcinoid syndrome, since they do not occur with other diseases. Unlike climacteric hot flashes, they are of four types:

in the first type, redness occurs in the face and neck, which lasts for several minutes;
at the second, the face becomes cyanotic, which lasts 5-10 minutes, while the nose swells and becomes purple-red;
in the third type, the duration of the tide can be from several hours to several days - the condition is characterized by lacrimation, the appearance of deep wrinkles on the face, dilation of the vessels of the face and eyes;
with the fourth type of tides, irregularly shaped red spots appear on the neck and arms of a person.

Diagnosis and treatment

Diagnosis of a condition such as carcinoid syndrome is difficult, since all the symptoms of the pathology are common, and if there is no characteristic flushing of the face or hot flashes, it is difficult to determine the disorder that caused these symptoms, so patients are prescribed a comprehensive examination, which includes:

testing for biochemistry;
immunofluorescent studies;
instrumental research methods.

The most informative instrumental methods are CT and magnetic resonance imaging, which allow detecting neoplasms in organs even at an early stage of development, which increases the patient's chances of recovery. But other instrumental methods are also prescribed, which diagnostics has at its disposal: radiography, scintigraphy, endoscopy, phlebo- and arteriography.

The treatment of such a pathological condition as carcinoid syndrome includes the treatment of the root cause, that is, the tumor. The treatment method allows you to determine the diagnosis, since it shows the localization of the tumor, its stage of development and other criteria that are important for developing a treatment plan.

The main methods of cancer treatment today are:

surgical excision of the tumor;
chemotherapy;
radiation therapy;
symptomatic treatment.

The main method is the surgical removal of the neoplasm, which can be radical, palliative and minimally invasive. Radical excision involves the removal of the area affected by the tumor, adjacent tissues and lymph nodes, as well as metastases in the body.

Palliative surgery involves the removal of only the primary tumor and the largest metastases. Minimally invasive surgery includes ligation of the hepatic vein, which makes it possible to get rid of symptoms such as hot flashes and diarrhea. After surgical excision, a complex of chemotherapy drugs is prescribed to destroy metastases in the body and the remnants of the tumor (if any). The complex use of surgical methods and chemotherapy allows you to prolong the life of the patient, and in some cases (when the tumor is detected at an early stage) and completely recover.

As for symptomatic treatment, it is necessary to alleviate the patient's condition. For this purpose, serotonin antagonists, H1 and H2 receptor blockers, antidepressants, alpha interferon and other drugs are prescribed.

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Diseases with similar symptoms:

Intestinal obstruction is a severe pathological process, which is characterized by a violation of the process of release of substances from the intestine. This disease most often affects people who are vegetarians. There are dynamic and mechanical intestinal obstruction. If the first symptoms of the disease are detected, it is necessary to go to the surgeon. Only he can accurately prescribe treatment. Without timely medical attention, the patient may die.

ICD-10 code

Carcinoid (carcinoid syndrome) is a rare potentially malignant hormonally active tumor originating from argentophilic cells. Most often, carcinoid tumors are localized in the gastrointestinal tract, less often they occur in the bronchi, gall bladder, pancreas and ovaries. The size of tumors, as a rule, is not large and varies from 0.1 to 3 cm.

Carcinoid syndrome is a disease caused by the circulation of mediators, which is manifested by reddening of the skin (90%), diarrhea (75%), noisy breathing (20%), endocardial fibrosis (33%), damage to the valves of the right heart; sometimes there is pleural, peritoneal or retroperitoneal fibrosis.

The reasons

The etiology of carcinoid, like other tumors, is still unclear. The origin of many symptoms of the disease is due to the hormonal activity of the tumor. A significant release of serotonin, lysylbradykinin and bradykinin, histamine, prostaglandins by tumor cells has been proven.

The development of carcinoid syndrome is due to a hormonally active tumor originating from enterochromaffin (argentaffin) intestinal cells (Kulchitsky cells). At the same time, hypertensive syndrome accompanies increasing intestinal disorders.

Classification

One of the most appropriate approaches to the classification of carcinoid tumors of the gastrointestinal tract is their division according to embryogenesis into anterior, middle, and posterior. In accordance with this, there are:

Carcinoid tumors of the anterior part of the digestive tube (bronchi, stomach, duodenum, pancreas); these neoplasms are argentaffin-negative, contain a small amount of serotonin, sometimes secrete 5-hydroxytryptophan and ACTH, are able to metastasize to the bones;
Carcinoids of the middle part of the digestive tube (lean, ileum, right colon) are argentaffin-positive, contain a lot of serotonin, rarely secrete serotonin or ACTH, rarely metastasize;
Carcinoid tumors of the posterior part of the digestive tube (transverse colon, descending colon and rectum) are argentaffin-negative, rarely contain serotonin and ACTH, and can metastasize to the bones. Sometimes they are also found in the gonads, prostate, kidneys, mammary glands, thymus, or skin.

Symptoms

Symptoms, the course of carcinoid are made up of local symptoms caused by the tumor itself, and the so-called carcinoid syndrome, due to its hormonal activity. Local manifestations are local soreness; often there are signs resembling acute or chronic appendicitis (with the most frequent localization of the tumor in the appendix) or symptoms of intestinal obstruction, intestinal bleeding (with localization in the small or large intestine), pain during defecation and excretion of scarlet blood with feces (with rectal carcinoid ), weight loss, anemia. Carcinoid syndrome includes peculiar vasomotor reactions, attacks of bronchospasm, hyperperistalsis of the gastrointestinal tract, characteristic skin changes, lesions of the heart and pulmonary artery. In a pronounced form, it is not observed in all patients, more often with tumor metastases to the liver and other organs, especially multiple ones.

Typical symptoms are:

Hyperemia
Diarrhea
Abdominal pain
Wheezing due to bronchospasm (narrowing of the airways)
valvular heart disease
Surgery can cause a complication known as a carcinoid crisis.

Hyperemia is the most common symptom of carcinoid syndrome. In 90% of patients, hyperemia occurs during the disease. Flushing is characterized by redness or discoloration of the face and neck (or upper body), as well as fever. Attacks of flushing usually occur suddenly, spontaneously, they can also be caused by emotional stress, physical stress, or drinking alcohol.

Attacks of hyperemia can last from minutes to several hours. Flushing may be accompanied by a rapid heartbeat, low blood pressure, or dizzy spells if blood pressure drops too low and no blood is flowing to the brain. Rarely hyperemia is accompanied by high blood pressure. The hormones that are responsible for flushing are not fully recognized.

Diarrhea is the second important symptom of carcinoid syndrome. Approximately 75% of patients with carcinoid syndrome have diarrhea. Diarrhea often occurs along with flushing, but can also occur without it. In carcinoid syndrome, diarrhea is most often due to serotonin.

Heart disease occurs in 50% of patients with carcinoid syndrome. Carcinoid syndrome usually leads to scarring and stiffness of the pulmonary valve on the right side of the heart. Stiffness of these two valves reduces the heart's ability to pump blood from the right ventricle to the lungs and other parts of the body, which can lead to heart failure.

Typical symptoms of heart failure include an enlarged liver (due to the heart's supply of blood in heart failure, when it is unable to pump all the incoming blood), swelling of the legs and ankles (dropsy), swelling of the abdomen due to fluid accumulation (abdominal dropsy). The cause of damage to the tricuspid and pulmonary valves of the heart in carcinoid syndrome, in most cases, is the intense long-term effect of serotonin on the blood.

A carcinoid attack is a dangerous condition that can occur during surgery. It is characterized by a sudden drop in pressure that causes shock, sometimes accompanied by an excessively rapid heart rate, elevated blood glucose levels, and severe bronchospasm.

A carcinoid attack can be fatal. The best way to prevent a carcinoid attack is surgery.

Wheezing occurs in about 10% of patients with carcinoid syndrome. Wheezing is a consequence of bronchospasm (spasm of the airways), which occurs as a result of the release of hormones by a carcinoid tumor.

Abdominal pain is a common symptom in patients with carcinoid syndrome. Pain may occur due to liver metastases, due to the fact that the tumor affects neighboring tissues and organs, or intestinal obstruction.

Diagnostics

The diagnosis is confirmed by a high content of sorotonin in the blood plasma, increased urinary excretion of 5-hydroxyindoleacetic acid, as well as the detection of a tumor of the intestine, liver, and lungs during instrumental research methods. Biochemical parameters can be distorted when eating foods containing a large amount of serotonin (bananas, walnuts, citrus fruits, kiwi, pineapples), taking rauwolfia preparations, phenothiazines, salicylates, as well as in pathological conditions complicated by intestinal obstruction, when the excretion of 5-hydroxyindoleacetic acid may increase to 9–25 mg/day.

Immunofluorescent studies confirm the presence of neuropeptides (serotonin, substance P and neurotensin) in carcinoid tumors. Determination of carcinoembryonic antigen (CEA) in the diagnosis of carcinoid tumors also has a certain meaning: its level is usually normal or minimal. If the CEA concentration is elevated, another tumor should be suspected.

Comprehensive topical diagnosis of carcinoids includes X-ray examination, computed tomography, ultrasound scanning, the use of immunoautoradiographic methods for determining hormones in the blood, selective arterio - and phlebography, scintigraphy with indium-111-octreotide and morphological examination of the biopsy. The use of the entire complex of modern research methods (fluoroscopy, endoscopy, selective arterio- and phlebography, ultrasound, computed tomography, radionuclide studies, determination of hormones in the blood, immunohistochemical examination of tumor biopsy specimens) provides a correct diagnosis in 76.9% of cases.

Treatment

Considering the general principles of therapy for carcinoid syndrome, it should be noted that the earliest removal of the tumor is advisable. However, it must be remembered that the clinical manifestations of carcinoid syndrome very often occur in cases where there are already functionally active liver metastases. In this case, radical surgical treatment is not feasible. However, mitigation of the carcinoid syndrome clinic can be achieved by excising as many metastases as possible, thus reducing the total amount of serotonin-producing tissue. If surgical intervention is not possible for any reason, X-ray therapy can be used, the effectiveness of which, however, is low due to the resistance of carcinoid tumors to radiation exposure. After radiation therapy, there are no reliable data on the increase in life expectancy.

Among the drugs used in the treatment of carcinoid tumors, cyclophosphamide should be singled out, the effectiveness of which, according to a number of authors, is about 50%. There are also reports that a good therapeutic effect is noted when prescribing serotonin antagonists, of which cyproheptadine and deseryl have found the most widespread use. Cyproheptadine has not only antiserotonin, but also antihistamine action. It is administered intravenously at a dose of 6 to 40 mg. Deseryl is used orally at a dose of 6 to 24 mg and intravenously for 1-2 hours at a dose of 10-20 mg.

Some antidepressants - fluoxetine, sertraline, fluvoxamine, paroxetine - can be used for symptomatic therapy.

Histamine H1 and H2 receptor blockers (cimetidine, ranitidine, diphenhydramine/diphenhydramine) are effective in carcinoids producing predominantly histamine. Loperamide (Imodium) is used to treat diarrhea.

Synthetic analogues of somatostatin - octreotide (sandostatin) and lanreotide (somatulin) - are widely used to treat carcinoid syndrome. Sandostatin, interacting with somatostatin receptors, inhibits the production of active substances by the tumor. The recommended regimen for the use of sandostatin (octreotide) in the treatment of carcinoid and neuroendocrine syndromes is 150-500 mcg subcutaneously 3 times a day. The drug increases the survival of patients with carcinoid tumors and the presence of metastases, improves the quality of life of patients, facilitating or eliminating hot flashes, intestinal motor dysfunction, diarrhea.

Conducted numerous studies on the use of a-interferon in patients with carcinoid tumors. For the treatment of patients used doses of a-interferon 3-9 IU subcutaneously 3-7 times a week. The use of higher doses of the drug does not improve treatment rates, but significantly increases the percentage of toxic reactions. In the treatment of a-interferon improvement is observed in 30-75% of cases.

Treatment of arterial hypertension is carried out according to the general rules. In some cases, treatment should be aimed at combating the complications of carcinoid syndrome, such as cardiovascular insufficiency, gastrointestinal bleeding, etc. It should be noted that the duration of the disease (10 years or more), significant depletion of patients with carcinoid syndrome requires general strengthening therapy.

Thus, the main type of treatment for patients with carcinoid and neuroendocrine tumors is the surgical method. Their drug treatment is based on chemotherapy, the use of somatostatin analogues and a-interferons.

Dizziness
Nausea
Abdominal pain
Elevated temperature
Red spots on the hands
Cardiopalmus
Vomit
Diarrhea
Red spots on the neck
Facial redness
lacrimation
Neck redness
Hot flashes
Swelling of the limbs
Redness of the nose
Rattling in the chest
Accumulation of fluid in the abdominal cavity
Nose swelling
Blueness of the face
The appearance of deep wrinkles on the face

It turns out that the root cause of the development of such a pathological condition is a tumor in any of the organs. In this case, a hormone-producing tumor can be located:

in the appendix;
in the small or large intestine;
in the stomach.

The reasons

Predisposing factors for the development of this pathological condition may be:

hereditary predisposition (in particular, multiple endocrine neoplasias);
gender - pathology is more often observed in men;
excessive drinking and smoking;
certain types of neurofibromatosis;
history of stomach disease.

In addition, different forms of carcinomas occur in people of different races. Thus, African Americans are more likely to experience stomach tumors, while Europeans have lung carcinomas.

Symptoms

diarrhea;
paroxysmal abdominal pain;
nausea and vomiting.

Tumors of the appendix are even rarer, and often the prognosis for removing the appendix is favorable in cases where the tumor is small and does not metastasize.

The most common neuroendocrine carcinoma is gastric, which is of three types and has a high probability of metastasis:

Type I is a tumor less than 1 cm in size. It is often benign, so the prognosis in the treatment of pathology is favorable;
Type II - a neoplasm up to 2 cm in size, which rarely degenerates into a malignant tumor;
Type III is the most common - these are tumors up to 3 cm in size, which are malignant and often grow into surrounding tissues. The prognosis, even with timely diagnosis, is poor. But, if a tumor is detected at an early stage during a preventive examination and treated comprehensively, then it is possible to provide a person with 10–15 years of a full life, which is already a lot, taking into account a difficult diagnosis.

So, the main symptoms of a condition such as carcinoid syndrome are:

diarrhea;
hyperemia;
abdominal pain;
wheezing;
pathology of the cardiovascular system;
tides.

In addition, some people may develop a carcinoid crisis, a life-threatening condition with severe consequences.

Other symptoms such as abdominal pain, wheezing in the lungs, and swelling of the extremities or accumulation of fluid in the abdominal cavity (which occurs with pathologies of the heart) are not characteristic - they can occur with any disease, so they are not of diagnostic value. But hot flashes, similar to those that women experience during menopause, can characterize the carcinoid syndrome, since they do not occur with other diseases. Unlike climacteric hot flashes, they are of four types:

in the first type, redness occurs in the face and neck, which lasts for several minutes;
at the second, the face becomes cyanotic, which lasts 5-10 minutes, while the nose swells and becomes purple-red;
in the third type, the duration of the tide can be from several hours to several days - the condition is characterized by lacrimation, the appearance of deep wrinkles on the face, dilation of the vessels of the face and eyes;
with the fourth type of tides, irregularly shaped red spots appear on the neck and arms of a person.

Diagnosis and treatment

testing for biochemistry;
immunofluorescent studies;
instrumental research methods.

The main methods of cancer treatment today are:

surgical excision of the tumor;
chemotherapy;
radiation therapy;
symptomatic treatment.

The main manifestations of carcinoid syndrome are diarrhea and hot flashes.

Hyperemia is the most common symptom that occurs. Almost ninety percent of patients who have this disease have signs of hyperemia. There is an increase in temperature, the face and neck become red. Redness can occur against the background of emotional stress, alcohol intake, physical work. Redness occurs suddenly and lasts from a few minutes to several hours. At the same time, the patient's pressure decreases, dizziness appears, and the heartbeat quickens. Some doctors believe that with an increase in serotonin, bradykinin and substance P, redness occurs and this symptomatology increases. Serotonin can cause diarrhea, histamine - wheezing, tachykinins - redness due to the fact that it dilates blood vessels.

Diarrhea - may occur with flushing or by itself. Doctors attribute diarrhea to the action of serotonin. Occurs in approximately 75% of patients. To reduce manifestations, codeine phosphate is used every six hours at 15 mg, loperamide - the initial dose is prescribed 4 mg once, and then 2 mg each, the maximum daily intake is 16 mg.

Heart problems - occur in half of patients with carcinoid syndrome. Carcinoid syndrome changes the connective tissue in the pulmonary valve of the heart. Due to the fact that the valve is thickened, affected by carcinoid syndrome, the heart begins to poorly pump blood from the right stomach to the lungs, other parts of the body, this leads to heart failure. With the development of heart failure, ascites occurs, the liver enlarges, and the legs swell. Such symptoms are caused by long-term and large amounts of serotonin in the blood.

Carcinoid crisis is the most dangerous condition that can occur during surgery. A sharp drop in blood pressure, increased blood glucose, palpitations, bronchospasm. A carcinoid crisis can lead to the death of the patient, so somatostatin is used before surgery to prevent a crisis.

Wheezing - occurs due to emerging bronchospasm as a result of the action of hormones that the tumor secretes.

Abdominal pain - often occurs in patients with carcinoid syndrome. Metastases spread to the liver and cause pain, or due to intestinal obstruction, since the tumor is more common in the intestine.

John A. Outes, L. Jackson Roberts II (John A. Oates, L. Jackson Roberts II)

In a carcinoid tumor accompanied by reddening of the skin of the face, telangiectasia, diarrhea, damage to the heart valves and narrowing of the bronchi, it is assumed that all these manifestations are due to the release of one biologically active substance or several from the tumor. Serotonin was the first of these substances to be discovered. Its hyperproduction serves as the most constant biochemical indicator of the carcinoid syndrome. However, it is not the only mediator of symptoms, as carcinoid tumors can produce both a variety of indoles and chemically unidentified substances, including vasoactive peptides and histamine. The latter substances can cause flushing of the skin. An extended classification of carcinoid tumors takes into account the wide variety of biologically active substances produced by them, as well as different mechanisms of their production and accumulation. In accordance with this, a wide range of clinical manifestations of carcinoid syndrome was noted.

Tumors.Carcinoid tumors are slow growing neoplasms composed of enterochromaffin cells. Metastatic tumors that cause carcinoid syndrome usually originate from small primary tumors of the ileum. This syndrome can also be caused by a neoplastic formation localized in the appendix, in organs derived from the embryonic anterior part of the digestive tract (bronchi, stomach, pancreas and thyroid glands), as well as developed from ovarian and testicular teratomas.

Carcinoid tumors are extremely prone to metastasizing to the liver (and metastases can be extensive) with minimal metastasis to other organs. Extrahepatic metastases include tumors in the bones, mainly represented by osteoblastic elements, as well as in the lungs, pancreas, ovaries, adrenal glands and other organs.

Primary carcinoid tumors are most often localized in the appendix, but they very rarely metastasize. From the large intestine, carcinoid can metastasize, but it almost never has hormonal activity.

A common carcinoid tumor of the ileum is histologically characterized by compact aggregations of cells of the same size and the same type of nuclei. The histochemical feature of these cells is a positive argentophilic reaction, when silver salts are converted to metallic silver. A positive argentophilic reaction is not required for diagnosis, however, organ carcinoid tumors that originate from the embryonic anterior digestive tract contain a small amount of argentophilic cells. Tumors of these organs are distinguished by a wide range of histological manifestations: for example, in the lungs - from a typical bronchial carcinoid to histological forms indistinguishable from oat cell carcinoma. Electron-microscopic examination always reveals electron-dense secretory granules in them.

Clinical manifestations.Unlike most metastatic tumors, carcinoid tumors are characterized by unusually slow growth, and therefore patients survive for 5-10 years from the time of diagnosis of carcinoid. The hormonal activity of these tumors causes both a wide range of clinical symptoms and a long period of illness. Death occurs as a result of heart or liver failure, as well as complications associated with tumor growth.

vasomotor response. Most often, the tumor is manifested by hyperemia of the skin in the form of erythematous reddening of the skin of the head and neck (the area of the rush of blood to the face). During the vascular reaction, the skin color may change from red to cyanotic, and then to pronounced pallor. Prolonged bouts of hyperemia may be accompanied by lacrimation and swelling of the periorbital region. The systemic effects of these reactions vary. They can be manifested by tachycardia and hypotension, however, sometimes blood pressure does not change. Hypertension is rarely recorded, and therefore the carcinoid syndrome cannot be considered its cause.

Skin hyperemia can be triggered by emotional factors (excitement and arousal), food intake and alcoholic beverages. In addition, pentagastrin and beta-adrenergic antagonists, such as epinephrine, may act as a trigger for vasodilation. Since the hemodynamic disturbances caused by these pharmacological agents can be pronounced, they should be prescribed with great caution.

Telangiectasia. In some patients with carcinoid syndrome, as a result of frequent and prolonged bouts of cutaneous vasodilation, telangiectasias may appear, first on the face and neck, and then in the zygomatic bone, where they are most pronounced.

Symptoms from the gastrointestinal tract. Vasomotor reactions are sometimes accompanied by increased peristalsis, "rumbling" in the abdomen with sudden pain attacks and acute development of diarrhea. However, more often diarrhea is chronic with a secretory component, in severe cases it is accompanied by a violation of absorption processes in the intestine.

Cardiovascular manifestations. A characteristic feature of the carcinoid syndrome is fibroelastosis of the endocardium and valves, predominantly in the right sections of the heart, but sometimes small changes are also detected in the left sections. Plaque-like thickenings of the endocardium, consisting of smooth muscle cells surrounded by a stroma rich in mucopolysaccharides, collagen and microfibrils, do not penetrate into the internal elastic membrane. Displacement of the valvular leaflets, tendinous cords and papillary muscles leads to dysfunction of the valves of the right heart, which can lead to their regurgitation, stenosis, or both. The fibrous process can cause extremely dangerous hemodynamic disturbances due to tricuspid valve insufficiency and stenosis of the pulmonary artery orifice. High cardiac output with concomitant impairment of cardiac function may be the result of either continuous release of vasodilators by the tumor or increased blood flow in tumor metastases.

Pulmonary symptoms. The narrowing of the bronchi occurs less frequently in carcinoid syndrome, it cannot be pronounced, especially during the period of increased vasomotor activity.

General symptoms. In addition to hormonal effects, a carcinoid tumor itself can cause intestinal obstruction or intestinal bleeding. Necrotic changes in a carcinoid tumor localized in the intestine or liver can cause abdominal pain, a general deterioration in the patient's well-being, fever and leukocytosis. With metastasiszah carcinoid syndrome is manifested by an increase in the size of the liver. The spread of liver metastases can occur before the results of liver function tests change. Sometimes carcinoid syndrome is accompanied by myasthenia gravis.

Hormonal activity of carcinoid tumor. The most constant characteristic of carcinoid tumors is the activity in them of tryptophan hydroxylase, which catalyzes the formation of 5-hydroxytryptophan (5-HTP) from tryptophan. Most carcinoid tumors also contain aromatic decarboxylase. L -amino acids, which catalyzes the formation of 5-hydroxytryptamine (serotonin). In carcinoid tumors of the stomach and other organs that have developed from the anterior part of the digestive tract of the embryo, decarboxylase activity is often reduced, as a result of which they release 5-GTP rather than serotonin. After release from the tumor, serotonin is inactivated by monoamine oxidase. In addition, it is absorbed by platelets, which also helps to remove free serotonin from the blood. Monoamine oxidase oxidizes serotonin to 5-hydroxyindoleacetaldehyde, which in turn, under the influence of aldehyde dehydrogenase, quickly turns into 5-hydroxyindoleacetic acid (5-HIAA). This acid is rapidly excreted in the urine, and almost all circulating serotonin can be measured by the amount of 5-HIAA excreted. Carcinoid tumors differ in their ability to accumulate serotonin, the concentration of which in the tumor tissue can range from a few micrograms per 1 g to 3 mg/g. The concentration of serotonin in the tumor tissue is not related to the intensity of its synthesis, corresponding to the urinary excretion of 5-HIAA. In short, tumors of the ileum tend to be more serotonin-accumulating than carcinoids localized in other organs that have developed ontogenetically from the anterior alimentary tract of the embryo.

In patients with carcinoid syndrome, tachykinin class peptides are determined in the tumor and blood. In this syndrome, several vasodilating peptides belonging to this class have been identified, including the non-decapeptide substance P. No specific substances of the tachykinin class, typical of the carcinoid syndrome, have yet been found.

Bradykinin, like vasodilating peptides, is released (but not always) during the period of increased vasomotor activity. In accordance with this, it cannot be considered the main specific substance that causes it in carcinoid syndrome.

Some carcinoid tumors, especially those of the stomach, produce and release large amounts of histamine, which can be detected by an increase in its amount in the urine. The release of histamine from the tumor causes sudden vasodilation, accompanied by hot flushes, tachycardia, and hypotension.

In a number of cases, carcinoid syndrome is accompanied by hyperadrenocorticism. It is caused by ectopic production of adrenocorticotropic hormone or corticotropin-releasing factor by tumors that are usually localized not in the ileum, but in other organs (bronchi, pancreas, ovaries and stomach).

In some cases, "multiple endocrine adenomas" accompany carcinoids localized in organs developed from the anterior part of the digestive tract of the embryo. These include parathyroid adenomas and pancreatic tumors that cause Zollinger-Ellison syndrome.

Tumors of organs embryogenetically associated with the anterior part of the digestive tract are similar in histological structure to carcinoid. They can produce very large amounts of gastrin, insulin, calcitonin, glucagon, corticotropin, growth hormone, growth hormone releasing factor, and vasoactive intestinal polypeptides in the absence of the usual clinical manifestations of the carcinoid syndrome. These carcinoid tumors seem to have a common embryogenetic origin with tumors that cause the development of the carcinoid syndrome.

Pathophysiology.Serotonin is responsible for the clinical manifestations of carcinoid syndrome associated with increased intestinal motility. In addition, an increase in its level in the blood can cause the deposition of fibrin in the endocardium.

The secondary effect of excess production of serotonin is also manifested in cases where a significant part of the dietary tryptophan is metabolized in the process of hydroxylation; while a smaller amount becomes available for the formation of nicotinic acid and proteins. With urinary excretion of 5-HIAA in excess of 200–300 mg/day, plasma tryptophan levels decrease and nicotinamide deficiency is detected.

The mechanism of paroxysmal vasodilation. Although paroxysmal vasodilation in patients with histamine-secreting gastric carcinoids may be due to the action of this amine, the mechanism of their onset is still not well understood. Current evidence suggests that serotonin does not mediate these seizures.

The release of substances that cause paroxysmal vasodilation, apparently, can also be triggered by catecholamines, since most often these attacks are not spontaneous, but are associated with excitement and other emotional factors. In the experiment, these attacks can be caused by the introduction of isoproterenol in an amount of less than 0.5 μg / day. Pentagastrin at doses less than 25 mcg also causes a sharp reddening of the skin, which often occurs during meals. These attacks can be stopped with somatostatin, which most likely inhibits the release of vasodilatory substances.

Diagnostics. With a full set of symptoms, carcinoid syndrome is easily recognized. Moreover, a diagnosis can be made even if only one of the symptoms is present. The diagnosis is confirmed by hyperproduction of 5-hydroxyindoles and increased urinary excretion of 5-HIAA, which normally should not exceed 9 mg/day. In a patient on a diet high in serotonin, the biochemical diagnosis of carcinoid may be difficult. So, for example, after taking large amounts of walnuts or bananas, which contain a significant amount of serotonin, the excretion of 5-HIAA in the urine increases. Some drugs also interfere with 5-HIAA urinary excretion biochemical tests and may cause a misdiagnosis of carcinoid syndrome. Urinary excretion of 5-HIAA is enhanced, for example, by the use of cough syrups containing guaiacolate, as well as some phenothiazines. After excluding the alimentary pathway of 5-hydroxyindoles, the diagnosis of carcinoid syndrome should be made if more than 25 mg/day is excreted in the urine. In carcinoid syndrome, non-tropical sprue, acute intestinal obstruction, 9-25 mg/day of 5-HIAA can be excreted.

Measuring the amount of serotonin in the blood or in platelets is less important for the diagnosis of carcinoid syndrome compared to the quantitative determination of its main metabolites in the urine. At the same time, the determination of an increased amount of serotonin in the tumor tissue serves as a necessary addition to the study of its histological structure in order to establish its carcinoid nature. Before performing a quantitative determination of serotonin in the tissue of a tumor suspected of carcinoid, a part of it should always be kept frozen.

The main directions of diagnosis for suspected carcinoid syndrome

1. Quantification of daily urinary excretion of 5-HIAA

2. If increased urinary excretion of 5-HIAA confirms the diagnosis of carcinoid syndrome, an attempt should be made to detect a primary tumor in the testicles, ovary, or bronchi

3. To resolve the issue of the possibility of excision of liver metastases, it is necessary: to establish the localization and nature of liver metastases using computed tomography, liver scintillation scanning, arteriography, ultrasound; assess the functional state of the liver and heart; look for extrahepatic metastases (in bones and other tissues)

4. In patients with intractable diarrhea, it is necessary to exclude a possible violation of absorption processes in the intestine (malabsorption)

Differential diagnosis. In cases where the patient has paroxysmal vasodilation without increased urinary excretion of 5-HIAA, other diagnostic features should be considered to confirm a carcinoid tumor and develop an associated carcinoid syndrome. However, it should be borne in mind that some pathological conditions associated with systemic activation of mast cells, including mastocytosis, can also be accompanied by sudden vasomotor attacks, hypotension, and even syncope without increasing the level of 5-HIAA in the urine. Sudden "tides" are typical of menopause, they accompany other tumors, to which, first of all, specific medullary thyroid carcinoma should be attributed.

variants of carcinoid syndrome.The origin of the tumor affects the production of its biologically active substances, their accumulation and release. Carcinoid tumors in organs embryogenetically associated with the anterior part of the digestive tract (bronchi, stomach, pancreas) differ significantly from tumors that have developed in organs originating from the distal midgut of the embryo. The latter cause the development of the classic carcinoid syndrome, in which the tumor always secretes serotonin with or without a small amount of 5-hydroxytryptophan (5-GTP). As a rule, the tumor contains a large amount of serotonin, and usually consists of dense compact aggregations of argentophilic cells.

Carcinoid tumors in organs developed from the anterior part of the digestive tract of the embryo, in contrast, contain less serotonin and argentophil cells and can secrete 5-GTP. These tumors appear to be more commonly associated with hyperadrenocorticism and multiple endocrine adenomas.

In addition to these common features, common to all carcinoid tumors of this group, carcinoids of the stomach and bronchi differ in specific clinical and biochemical features. Patients with carcinoid tumors of the stomach are characterized by unusual "hot flashes", which usually begin with the appearance on the skin of the face and neck of bright red erythematous spots with sharply defined tortuous borders, which eventually merge. Most likely, these attacks are provoked by food intake. Carcinoid tumors of the stomach are deficient in the enzyme decarboxylase and secrete 5-GTP. As a rule, they also secrete histamine, in connection with which patients often develop peptic ulcers. Diarrhea and cardiac disorders are not typical clinical manifestations of carcinoid tumors, which secrete abundantly 5-GTP and insufficiently produce serotonin.

In patients with carcinoid tumors of the bronchi, vasomotor attacks are especially prolonged and severe. They are accompanied by swelling of the periorbital tissues, excessive tearing and salivation, hypotension, tachycardia, restlessness or anxiety, and tremor. Nausea, vomiting, intractable diarrhea and bronchial constriction can progress, extremely aggravating the patient's condition.

These attacks can be prevented with the help of glucocorticoids, and chlorpromazine allows to stop their main manifestations to some extent.

Treatment.Treatment for carcinoid syndrome is directed, firstly, to reduce the mass of the tumor by surgery and/or with the help of chemotherapy drugs and, secondly, to alleviate and stop the symptoms caused by hormones.

After the diagnosis of carcinoid syndrome in some patients excised tumors that have developed from testicular or ovarian teratomas, as well as bronchi. Carcinoid tumors of this localization, in connection with the release of their secret directly into the systemic circulation, cause the development of the carcinoid syndrome even before the appearance of metastases. If humoral substances are released into the portal circulation system, they are largely metabolically neutralized by the liver, and therefore these tumors can cause the development of a carcinoid syndrome only after the formation of metastases, most often in the liver. Since carcinoid tumors grow relatively slowly, palliative resection of liver metastases in some cases can alleviate the patient's condition. Excision of large isolated liver metastases leads to a weakening of the clinical manifestations of the syndrome and a decrease in urinary excretion of 5-HIAA for several years. Sometimes, with multiple liver metastases, a lobe of the liver or the entire liver is resected. This operation is performed only if the metastases are localized mainly in the lobe of the liver to be resected. The volume of the operation is determined by the data of ultrasound examination of the liver, computed tomography, as well as examination of the surface of the liver during laparoscopy or laparotomy.

In patients with diffuse metastases in both lobes of the liver, a decrease in the tumor mass and a decrease in clinical symptoms can be achieved with surgical ligation or percutaneous embolization of the hepatic artery. Sufficient experience has not yet been accumulatedand similar operations, therefore, further study of the effectiveness of this method of treatment and possible postoperative complications is necessary.

Universal effective methods of chemotherapy have not been developed. In some cases, 5-fluorouracil, cyclophosphamide, streptozotocin, doxorubicin and methotrexate, used both individually and in various combinations, have a palliative effect. The objective response to this chemotherapy is low: the average duration of remission after a course of treatment is usually less than one year, in addition, almost all chemotherapy drugs have a pronounced toxic effect. Only in a very small proportion of patients, treatment with 5-fluorouracil is accompanied by mild toxicity. Initial doses of all chemotherapeutic agents should be small if more than 150 mg/day of 5-HIAA is excreted in the urine or if the patient has "hot flashes", since rapid lysis of tumor tissue under the influence of high doses can lead to a massive release of mediator substances and cause a "carcinoid crisis" . Radiation therapy can be effective at the stage of metastasis, for example in the bone. Some patients were tried to be treated with tamoxifen and leukocyte interferon.

A certain success may be accompanied by treatment with drugs whose action is directed to the humoral mediator substances of the tumor tissue. For example, in gastric carcinoids that produce and release a significant amount of histamine, its vasodilating effect can be blocked by a combination of H-1 (eg, diphenhydramine) and H-2 (cimetidine or ranitidine) antagonists. With diarrhea, treatment is mainly symptomatic (it is stopped with loperamide). In addition, serotonin antagonists, such as cyproheptadine and methysergide, can also be used for the same purpose, although long-term treatment with methysergide is associated with the risk of developing retroperitoneal fibrosis. To interrupt one of the steps in the synthesis of serotonin and relieve diarrhea, p-chlorophenylalanine, which inhibits the activity of tryptophan hydroxylase, is also used. Another drug - somatostatin - showed its effectiveness in the massive release of mediator substances by a carcinoid tumor, as well as in the phenomena of a "carcinoid crisis", since it sufficiently stopped the attacks of vasodilation, diarrhea and bronchial constriction that develop in this case. They prevent severe vasomotor attacks with glucocorticoids and relieve the clinical symptoms of carcinoid syndrome with phenothiazines, mainly in patients whose tumor is localized in the bronchi or in other organs that have developed fromanterior part of the digestive tract of the embryo.

At present, methods have not been developed that promote regression or at least partial suspension of the development of endocardial fibrosis in this disease, which makes surgical prosthetics of the affected fibrotic heart valves much more difficult.

With urinary excretion of 5-HIAA in an amount of approximately 100 mg / day, taking niacin prevents the development of pellagra in a patient.

Hypotension should not be treated with catecholamines, since epinephrine, norepinephrine, and other adrenergic drugs stimulate tumor release of vasodilators, which increase and prolong circulatory disturbances. If hypotension requires correction, then preference should be given to fluid replacement or the introduction of methoxamine.

T.P. Harrison. principles of internal medicine.Translation d.m.s. A. V. Suchkova, Ph.D. N. N. Zavadenko, Ph.D. D. G. Katkovsky