Carcinoid syndrome symptoms. Carcinoid syndrome: signs, diagnosis and treatment

- a complex of symptoms resulting from the hormonal activity of tumors from the cells of the APUD system. Includes hot flashes, persistent diarrhea, right heart fibrosis, abdominal pain, and bronchospasm. When carrying out surgical interventions, the development of a life-threatening carcinoid crisis is possible. Carcinoid syndrome is diagnosed on the basis of anamnesis, complaints, objective examination data, results of determining the level of blood hormones, CT, MRI, scintigraphy, radiography, endoscopy and other studies. Treatment - surgical removal of the tumor, drug therapy.

Carcinoid syndrome is a symptom complex observed in potentially malignant slow-growing neuroendocrine tumors that can occur in almost any organ. In 39% of cases, neoplasms that provoke carcinoid syndrome are localized in the small intestine, in 26% - in the appendix, in 15% - in the rectum, in 1-5% - in other parts of the large intestine, in 2-4% - in the stomach. , 2-3% - in the pancreas, 1% - in the liver and 10% - in the bronchi. In 20% of cases, carcinoid tumors of the gastrointestinal tract are combined with other neoplasms of the large intestine. Carcinoid syndrome usually develops at the age of 50-60 years, men and women suffer equally often.

Carcinoid was first described at the end of the 19th century. In the 1950s, a group of researchers led by Waldenström compiled an extended description of the histological and histochemical features of carcinoid tumors, and also proved the relationship between such neoplasms and the development of the carcinoid syndrome. For a long time, carcinoids were regarded as benign tumors, but recent research has shaken this view. It was found that, despite the slow growth, the formations have certain signs of malignancy and can metastasize to distant organs. The treatment of carcinoid syndrome is carried out by doctors working in the field of oncology, endocrinology, gastroenterology, cardiology, general surgery and other specialties.

Causes of the carcinoid syndrome

The cause of the development of carcinoid syndrome is the hormonal activity of tumors originating from the neuroendocrine cells of the APUD system. Symptoms are determined by changes in the levels of various hormones in the patient's blood. Typically, these neoplasms secrete large amounts of serotonin. As a rule, there is an increase in the production of histamine, prostaglandins, bradykinin and polypeptide hormones.

Carcinoid syndrome does not occur in all patients with carcinoid tumors. With carcinoids of the small and large intestine, this syndrome usually develops only after the appearance of metastases in the liver. This is due to the fact that hormones from the intestine with blood enter the liver through the portal vein system, and then are destroyed by liver enzymes. Metastasis to the liver leads to the fact that the products of tumor metabolism begin to directly enter the general circulation through the hepatic veins, without being cleaved in the liver cells.

With carcinoids localized in the lungs, bronchi, ovaries, pancreas and other organs, the carcinoid syndrome can develop before the onset of metastasis, since the blood from these organs does not pass through the portal vein system before entering the systemic circulation and is not “cleaned” in the liver tissue . Obviously malignant neoplasms cause carcinoid syndrome more often than tumors that do not show signs of malignancy.

An increase in serotonin levels provokes diarrhea, abdominal pain, malabsorption and heart disease. As a rule, with carcinoid syndrome, fibrous degeneration of the endocardium of the right half of the heart is observed. The left side of the heart is rarely affected because serotonin is destroyed as blood passes through the lungs. An increase in the amount of bradykinin and histamine causes hot flashes. The role of polypeptide hormones and prostaglandins in the development of carcinoid syndrome has not yet been elucidated.

Symptoms of the carcinoid syndrome

Hot flashes are the most common manifestation of carcinoid syndrome. This symptom is observed in 90% of patients. There is a sudden, periodic, paroxysmal reddening of the upper half of the body. Usually, hyperemia is especially pronounced in the face, neck and neck. Patients with carcinoid syndrome complain of feeling hot, numb, and burning. Hot flashes are accompanied by an increase in heart rate and a drop in blood pressure. There may be dizziness caused by a deterioration in the blood supply to the brain. During attacks, redness of the sclera and lacrimation may be observed.

In the initial stages of the development of carcinoid syndrome, hot flashes appear once every few days or weeks. Subsequently, their number gradually increases to 1-2 or even 10-20 times a day. The duration of hot flashes in carcinoid syndrome can range from 1-10 minutes to several hours. Typically, seizures occur on the background of drinking alcohol, spicy, fatty and spicy foods, physical activity, psychological stress, or taking medications that increase serotonin levels. Less often, hot flashes develop spontaneously, for no apparent reason.

Diarrhea is detected in 75% of patients with carcinoid syndrome. It occurs due to increased motility of the small intestine under the influence of serotonin. It has a chronic persistent character. The severity of the symptom can vary greatly. Due to malabsorption, all types of metabolism (protein, carbohydrate, fat, water-electrolyte) are disturbed, hypovitaminosis develops. With a long-term current carcinoid syndrome, drowsiness, muscle weakness, fatigue, thirst, dry skin and weight loss are noted. In severe cases, there are edema, osteomalacia, anemia and pronounced trophic changes in the skin, due to gross metabolic disorders.

Cardiac pathology is found in half of patients suffering from carcinoid syndrome. As a rule, endocardial fibrosis is detected, accompanied by damage to the right half of the heart. Fibrotic changes cause failure of the tricuspid and pulmonary valves and provoke stenosis of the pulmonary trunk. Valve failure and stenosis of the pulmonary artery in carcinoid syndrome can lead to the development of heart failure and stagnation in the systemic circulation, which are manifested by edema of the lower extremities, ascites, pain in the right hypochondrium due to liver enlargement, swelling and pulsation of the neck veins.

In 10% of patients with carcinoid syndrome, the phenomena of bronchospasm are observed. Patients are disturbed by attacks of expiratory dyspnea, accompanied by wheezing and buzzing wheezing. Another fairly common manifestation of carcinoid syndrome is abdominal pain, which may be due to a mechanical obstruction to the movement of intestinal contents due to the growth of the primary tumor or the occurrence of secondary foci in the abdominal cavity.

A terrible complication of the carcinoid syndrome can be a carcinoid crisis - a condition that occurs during surgical interventions, accompanied by a sharp decrease in blood pressure, increased heart rate, pronounced bronchospasm and an increase in blood glucose levels. The shock that occurs during a carcinoid crisis poses an immediate threat to the patient's life and can be fatal.

Diagnostics of the carcinoid syndrome

The oncologist establishes the diagnosis on the basis of characteristic symptoms, external examination data and objective studies. An increased level of serotonin is detected in the blood plasma. In the urine, a high content of 5-hydroxyindoleacetic acid is determined. To exclude a false positive result, within 3 days before testing, a patient with suspected carcinoid syndrome is advised to refrain from taking foods containing a large amount of serotonin (walnuts, eggplant, avocados, tomatoes, bananas, etc.) and certain medications.

In doubtful cases, tests with alcohol, catecholamines, or calcium gluconate are performed to stimulate hot flashes. To determine the localization of the tumor and identify metastases, a patient with carcinoid syndrome is sent for CT and MRI of internal organs, scintigraphy, radiography, gastroscopy, colonoscopy, bronchoscopy and other studies. In the presence of sufficient indications, laparoscopy can be used. Carcinoid syndrome is differentiated from systemic mastocytosis, hot flashes during menopause, and side effects when taking certain medications.

Treatment of carcinoid syndrome

The main method of treatment is surgery. Depending on the localization and prevalence of the process, radical excision of the primary focus or various palliative operations is possible. In case of carcinoid syndrome caused by tumors of the small intestine, resection of the small intestine is usually performed along with a portion of the mesentery. In case of damage to the large intestine and neoplasms located in the region of the ileocecal sphincter, a right-sided hemicolectomy is performed.

In case of carcinoid syndrome caused by a neoplasm in the appendix area, an appendectomy is performed. Some oncologists additionally remove nearby lymph nodes. Palliative surgical interventions are indicated at the stage of metastasis, include the removal of large foci (both secondary and primary) to reduce hormone levels and reduce the severity of carcinoid syndrome. Another way to reduce the manifestations of the carcinoid syndrome is embolization or ligation of the hepatic artery.

The indication for chemotherapy in carcinoid syndrome is the presence of metastases. In addition, this method of treatment is used in the postoperative period with heart damage, liver dysfunction and a high level of 5-hydroxyindoleacetic acid in the urine. To avoid the development of a carcinoid crisis, treatment is started with small doses of drugs, gradually increasing the dosage. The effectiveness of chemotherapy in carcinoid syndrome is low. A significant improvement is noted in no more than 30% of patients, the average duration of remission is 4-7 months.

As a symptomatic therapy for carcinoid syndrome, serotonin antagonist drugs are prescribed: fluoxetine, sertraline, paroxetine, etc. For tumors that produce a large amount of histamine, diphenhydramine, ranitidine and cimetidine are used. To eliminate diarrhea, it is recommended to take loperamide. In addition, lanreotide and octreotide are widely used in carcinoid syndrome, which suppress the secretion of biologically active substances in the neoplasm and can significantly reduce the manifestations of this syndrome in more than half of patients.

The prognosis for carcinoid syndrome is determined by the prevalence and degree of malignancy of the tumor. With a radical removal of the primary focus and the absence of metastases, a complete recovery is possible. With metastasis, the prognosis worsens. Due to the slow progression of carcinoid, life expectancy in such cases ranges from 5 to 15 years or more. The cause of death is multiple metastases to distant organs, exhaustion, heart failure or intestinal obstruction.

Carcinoids- the most common tumors from neuroendocrine cells (cells of the APUD system). These cells are derivatives of the neural crest. They are widely distributed in the body, contain and secrete some biologically active peptides. Most often, carcinoids develop in the gastrointestinal tract (85%), especially in the small intestine, and also in the lungs (10%), less often affecting other organs (eg, ovaries). Intestinal carcinoids rarely (in 10% of cases) manifest clinically. This is due to the rapid destruction of biologically active peptides in the liver. Only with metastases of intestinal carcinoid to the liver, symptoms appear in 40-45% of patients. As for ovarian carcinoids and bronchial carcinoids, they are able to cause a characteristic syndrome in the early stages of the disease.

Carcinoid syndrome- a combination of symptoms that have arisen due to the release of hormones by tumors and their entry into the bloodstream.

Pathogenesis (what happens?) during Carcinoid Syndrome:

Carcinoid tumors can appear where there are enterochromaffin cells, basically all over the body. A greater number of carcinoid tumors (65%) develop in the gastrointestinal tract. In most cases, a carcinoid tumor develops in the small intestine, appendix, and rectum. Least of all, carcinoid tumors develop in the stomach and colon; the pancreas, gallbladder, and liver are least likely to develop a carcinoid tumor (despite the fact that a carcinoid tumor usually metastasizes to the liver).

Approximately 25% of carcinoid tumors affect the airways and lungs. The remaining 10% can be found anywhere. In some cases, doctors cannot locate a carcinoid tumor despite symptoms of carcinoid syndrome.

Carcinoid tumor of the small intestine

In general, tumors of the small intestine (benign or malignant) are rare, much rarer than a tumor of the colon or stomach. Small carcinoid tumors of the small intestine may cause no symptoms other than mild abdominal pain. For this reason, it is difficult to determine the presence of a carcinoid tumor of the small intestine at an early stage, at least until the patient is operated on. It is possible to detect only a small proportion of carcinoid tumors of the small intestine in the early stages, and this occurs unexpectedly on x-rays. Usually, carcinoid tumors of the small intestine are diagnosed in the later stages, when the symptoms of the disease have made themselves felt and usually after metastases have appeared.

Approximately 10% of carcinoid tumors of the small intestine become the cause of the carcinoid syndrome. Usually, the development of carcinoid syndrome means that the tumor is malignant and has reached the liver.

Carcinoid tumors often obstruct the patency of the small intestine when they reach a large size. Symptoms of small bowel obstruction include paroxysmal abdominal pain, nausea and vomiting, and sometimes diarrhea. Obstruction can be caused by two different mechanisms. The first mechanism is an increase in the tumor inside the small intestine. The second mechanism is torsion of the small intestine due to fibrosing mesenteritis, a tumor-induced condition in which extensive scarring occurs in tissues in close proximity to the small intestine. Fibrosing mesenteritis sometimes obstructs the arteries that carry blood to the intestines, which can result in the death of part of the intestine (necrosis). In this case, the intestines can break through, which is a serious threat to life.

Appendicular carcinoid tumor

Although tumors in the appendix region are quite rare, carcinoid tumors are the most common tumors in the appendix region (about half of all appendix tumors). In fact, carcinoid tumors are found in 0.3% of cases of removed appendixes, but most of them do not reach more than 1 cm in size and do not cause any symptoms. In most cases, they are found in appendixes removed for non-tumor reasons. Representatives of many institutions believe that appendectomy is the most appropriate treatment for such small appendicular carcinoid tumors. The chances that the tumor will recur after an appendectomy are very low. Appendicular carcinoid tumors larger than 2 cm in 30% can be malignant and form local metastases. Thus, larger carcinoid tumors should be removed. A simple appendectomy will not help in this case. Fortunately, large carcinoid tumors are rare. Carcinoid tumors in the appendix, even in the presence of metastases to local tissues, usually do not cause carcinoid syndrome.

Rectal carcinoid tumors

Rectal carcinoid tumors are often diagnosed incidentally during plastic sigmoidoscopy or colonoscopy. Carcinoid syndrome is rare in rectal carcinoid tumors. The likelihood of metastasis formation correlates with the size of the tumor; 60-80% chance of metastases for tumors larger than 2 cm. For carcinoid tumors less than 1 cm, 2% chance of metastases. Thus, small rectal carcinoid tumors are usually successfully removed, but larger tumors (greater than 2 cm) require extensive surgery, which may even lead to partial removal of the rectum in some cases.

Gastric (gastric) carcinoid tumors

There are 3 types of gastric (gastric) carcinoid tumors: type I, type II and type III.

Gastric carcinoid tumors of the first type are usually less than 1 cm in size and are benign. There are complex tumors that spread throughout the stomach. They usually appear in patients with pernicious anemia or chronic atrophic gastritis (a condition in which the stomach stops producing acid). Lack of acid causes cells in the stomach that make the hormone gastrin to secrete large amounts of gastrin into the bloodstream. (Gastrin is a hormone secreted by the body to increase the activity of stomach acid. The acid in the stomach blocks the production of gastrin. In pernicious anemia or chronic atrophic gastritis, the lack of acid is the result of an increase in the amount of gastrin). Gastrin also has an effect on the transformation of enterochromaffin cells in the stomach into a malignant carcinoid tumor. Treatment for type 1 carcinoid tumors includes drugs such as somatostatin-containing drugs that stop the production of gastrin or surgical removal of the part of the stomach that produces gastrin.

The second type of gastric carcinoid tumor is less common. Such tumors grow very slowly and the probability of their transformation into a malignant tumor is very small. They appear in patients with a rare genetic disorder, such as MEN (multiple endocrine neoplasia) type I. In such patients, tumors occur in other endocrine glands, such as the pineal gland, parathyroid gland, and pancreas.

The third type of gastric carcinoid tumor is tumors larger than 3 cm that are isolated (appearing one or more at a time) in a healthy stomach. Tumors of the third type are usually malignant and there is a high probability of their deep penetration into the walls of the stomach and the formation of metastases. Tumors of the third type can cause abdominal pain and bleeding, as well as symptoms due to carcinoid syndrome. Gastric carcinoid tumors of the third type usually require surgery and removal of the stomach, as well as nearby lymph nodes.

Colon carcinoid tumors

Colon carcinoid tumors usually form on the right side of the colon. Like small bowel carcinoid tumors, colon carcinoid tumors are often found in advanced stages. Thus, the average tumor size at diagnosis is 5 cm, and metastases are present in 2/3 of patients. Carcinoid syndrome is rare in colon carcinoid tumors.

Symptoms of Carcinoid Syndrome:

Symptoms of the carcinoid syndrome differ depending on which hormones the tumors have secreted. These are usually hormones such as serotonin, bradykinin (which promotes pain), histamine, and chromogranin A.

Typical manifestations of carcinoid syndrome:

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

Hyperemia

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 be caused by emotional, physical stress or alcohol intake. Attacks of hyperemia can last from minutes to several hours. Flushing can be accompanied by a rapid heartbeat, low blood pressure, or dizzy spells if blood pressure drops too low and no blood flows to the brain. Rarely hyperemia is accompanied by high blood pressure. The hormones that are responsible for hyperemia are not fully recognized; these may include serotonin, bradykinin, and substance P.

Diarrhea

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. Drugs that block the action of serotonin, such as ondansetron (Zofran), often relieve diarrhea. Sometimes diarrhea in carcinoid syndrome can occur due to local effects of the tumor, which makes it difficult to pass the small intestine.

Heart disease

Heart disease occurs in 50% of patients with carcinoid syndrome. Carcinoid syndrome usually leads to fibrotic changes in the pulmonary valve of the heart. Valve dysfunction 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, swelling of the legs, and fluid in the abdomen (ascites). The cause of damage to the tricuspid and pulmonary valves of the heart in carcinoid syndrome, in most cases, is intense long-term exposure to serotonin.

Carcinoid crisis

Carcinoid crisis is a dangerous condition that can occur during surgery. The crisis is characterized by a sudden drop in blood pressure, which is the cause of the development of shock. This condition may be accompanied by excessive heart palpitations, high blood glucose levels, as well as severe bronchospasm. A carcinoid crisis can be fatal. The best way to prevent a carcinoid attack is with somatostatin surgery before surgery.

Wheezing

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

Abdominal pain is a common symptom in patients with carcinoid syndrome. Pain can occur due to liver metastases, due to the fact that the tumor affects neighboring tissues and organs, or due to intestinal obstruction (read below about carcinoid tumor of the small intestine).

Diagnosis of Carcinoid Syndrome:

Diagnosis of carcinoid syndrome is confirmed by an increase in the daily urine level of the metabolite of serotonin - 5-hydroxyindoleacetic acid.

Treatment of Carcinoid Syndrome:

Treatment of carcinoid syndrome: radical surgical removal of the tumor. For metastases that cannot be removed, octreotide therapy, a long-acting analogue of somatostatin, is prescribed.

With frequent attacks, methyldopa preparations are used (dopegyt 0.25-0.5 g 3-4 times a day), opium preparations for diarrhea. Perhaps the use of prednisolone at a dose of up to 20-30 mg per day.

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Other diseases from the Oncological diseases group:

The occurrence of carcinoid syndrome is determined by several reasons. Of essential importance are: the slow growth of the primary tumor, massive metastasis and the size of metastases. However, the extraportal location of the latter plays a decisive role. All these factors cause hypersecretion of serotonin and other biologically active substances that periodically enter the bloodstream and have a pathological effect on various organs and systems.

The most characteristic group of vasomotor disorders is the so-called "reddening syndrome" (flushing syndrome), described in detail by Waldenstrom and Thorson. First of all, there are periodic "redness" of the face, shoulders, upper body, accompanied by a burning sensation, heat, palpitations, tachycardia, a feeling of weakness, and sometimes profuse sweating. The color of the skin suddenly becomes bright red, and then rather quickly changes to pink and goes to a normal shade. Often, spots of cyanosis (“spotted cyanosis”) remain on the skin against the background of general pallor. Such an attack lasts from 30 seconds to 10 minutes. During the day, the patient has from 5 to 30 such attacks.

Provoking factors for the "reddening syndrome" are: emotional and physical stress, abundant, hot food, alcohol intake, defecation.

Over time, hyperemia of the skin can become permanent, cyanosis progresses, and patients resemble patients with polycythemia (plethoric habitus) in their appearance. Sometimes there are telangiectasias.

Some researchers try to explain the cyanotic phase of the redness attack by a possible synergistic effect on the vascular system of serotonin and bradykinin, with the simultaneous administration of which to rats, spasm of venules and retrograde blood spasm in the capillaries occurred (Weiner and Altura, 1967).

Bouts of redness in gastric carcinoids begin with bright red patchy erythema with well-defined borders. Apparently, in such patients, in addition to serotonin, significant amounts of histamine and 5-hydroxytryptophan, a precursor of serotonin, periodically enter the bloodstream. The predominant formation of the latter by the tumor tissue is due to a deficiency of decarboxylase, which provides the synthesis of serotonin (Jones et al., 1968).

The carcinoid syndrome that occurs with tumors of the bronchus has specific features, bouts of redness are acute in appearance, often accompanied by fever, lacrimation, runny nose, nausea and vomiting, hypotension and oliguria (Sandler, 1968). Such "carcinoid crises" (Kahil et al., 1964) may be caused by direct rapid entry of humoral agents into the arterial system, bypassing the portal circulation. "Redness Syndrome" is sometimes accompanied by hypertension, as well as diarrhea and asthma attacks.

Diarrhea in some cases is combined with cramping pains in the abdomen, pronounced rumbling. This symptom is due to intestinal hyperperistalsis caused by increased secretion of serotonin, and possibly bradykinin. Both of these agents increase the tone of the smooth muscles of the bronchi, spasm them, which often leads to atypical attacks of bronchial asthma.

In addition to the “reddening syndrome”, with a functioning carcinoid, changes of a different nature can be observed on the skin.

Some patients develop "pellagra-like lesions" associated with endogenous hypovitaminosis PP, caused by a relative lack of tryptophan for the synthesis of nicotinic acid in the intestine. Hyperkeratosis occurs, the skin becomes dry, flaky, grayish-black areas of pigmentation form on the forearms and lower extremities, glossitis is noted.

Along with "pellagra-like lesions", focal hyperpigmentation of a diffuse nature may be observed, due to excessive deposition of serotonin destruction products in the skin. Skin metastases of carcinoid are sometimes painful.

In patients with carcinoid syndrome, insufficiency of the tricuspid valve and stenosis of the orifice of the pulmonary artery are determined in 40-50% of cases (Sjoerdsma, 1956). The pathogenesis of these lesions remains unclear, but most researchers are supporters of the "biochemical theory" of their occurrence. The latter considers endocardial damage (mainly proliferative, not inflammatory) in carcinoid syndrome as a result of hypersecretion of serotonin and other biologically active substances that primarily affect the endocardium and contribute to excessive growth of connective tissue.

Serotonin clearly increases the tone of the arterial vessels of the lungs (Page, 1958), which creates an additional load on the right ventricle. The latter hypertrophies early, and then its myogenic dilatation quickly sets in with stagnation in the systemic circulation.

In the origin of edema in carcinoid syndrome, in addition to hemodynamic factors, hypoalbuminemia is involved due to a lack of tryptophan for protein synthesis, as well as a systematic increase in venous pressure in the midst of bouts of "redness". The antidiuretic effect of serotonin also plays a certain role, and in some patients, an increased concentration of antidiuretic hormone.

Patients suffering from carcinoid syndrome for a long time become emaciated, in some cases the weight is maintained.

Sometimes there are severe dizziness, transient visual impairment caused by cerebral hypoxia.

This is a combination of symptoms caused by the presence of a neuroendocrine tumor (carcinoid) in the body and its release into the blood of a large amount of hormones. Carcinoids produce about forty biologically active substances, but the most important among them are serotonin, histamine, tachykinin, kalikrein and prostaglandin. Neuroendocrine tumors can occur in any organ of the digestive system (often in the small intestine), as well as in the bronchi.

Signs of carcinoid syndrome

Sudden reddening of the skin of the face, neck, and chest, caused by a rush of blood to these areas of the body, is a hallmark of carcinoid syndrome. This symptom is recorded in approximately 85% of people with neuroendocrine tumors.

The course of such an attack differs in patients with different localizations of the tumor. So, in patients with intestinal carcinoid, such flushes of blood to the face and trunk occur suddenly and last from thirty seconds to half an hour. At this time, a person overtakes a feeling of heat. Severe attacks are accompanied by a drop in blood pressure and increased heart rate. As the disease progresses, attacks may become more frequent and prolonged, and the skin may become bluish.

The syndrome can occur spontaneously, or be triggered by food intake, alcohol, stress, defecation, exposure to anesthesia, and other factors. Seizures provoked by the effects of anesthesia can last for hours and be accompanied by a pronounced drop in blood pressure. This phenomenon in medicine is called a carcinoid crisis.

Another sign of carcinoid syndrome is the appearance of venous telangiectasias on the skin. This is an expansion of small vessels, which manifests itself in the form of spider veins or nets on the skin. Telangiectasias in carcinoid syndrome often occur in the region of the upper lip, nose, and cheekbones.

An equally significant symptom is diarrhea, which is recorded in approximately 80% of patients with neuroendocrine tumors. The frequency of stools can vary from several times to thirty per day. Feces are usually watery, without blood impurities. Diarrhea may be accompanied by abdominal pain.

Approximately 10-20% of patients complain of shortness of breath and the appearance of wheezing, more often occurring during bouts of reddening of the skin of the face and trunk.

Carcinoid syndrome is characterized by the deposition of fibrin plaques on the heart valves, the walls of the chambers, as well as on the inner walls of the pulmonary artery and aorta. The right side of the heart is most commonly affected. Such changes lead to valvular insufficiency. This symptom occurs in 40% of patients.

If the carcinoid tumor is localized in the stomach or bronchi, the course of an attack of carcinoid syndrome may differ. When the tumor is localized in the stomach, the skin may turn red in spots, while the person is worried about severe itching. Diarrhea and heart failure are rare. The symptoms of carcinoid syndrome with such localization of the tumor are caused by the biologically active substance histamine.

In patients with a carcinoid tumor localized in the bronchi, hot flashes are more severe and prolonged, sometimes lasting several days. These attacks may be accompanied by disorientation, anxiety, tremors (trembling of body parts). In addition, these patients experience symptoms such as:

1. swelling of the skin around the eyes;
2. lacrimation;
3. Increased salivation;
4. Hypotension (low blood pressure);
5. Heart palpitations;
6. Diarrhea;
7. Dyspnea;
8. Oliguria (decreased volume of urine).

It is believed that these symptoms in bronchial carcinoid tumors are caused by the influence of histamine secreted by the tumor itself.

Symptoms

There are also less significant symptoms that occur with carcinoid tumors. So, a violation of tryptophan metabolism with excessive formation of serotonin can lead to vitamin PP deficiency, which manifests itself in the form of pellagra. This disease is characterized by symptoms such as diarrhea, dermatitis (inflammation of the skin) and dementia (dementia).

Carcinoid tumors can also affect protein metabolism. As a result of impaired protein synthesis, muscle weakness and even atrophy develop.

Patients with severe bouts of redness may experience persistent swelling in the face, less often in the extremities.

Diagnostics

The symptoms of carcinoid syndrome are not specific, that is, they can also appear in other diseases, such as IBS (irritable bowel syndrome) or colitis, so it is extremely important to determine that the change in the patient's condition is caused precisely by the presence of neoplasms in the body.

To analyze for carcinoid syndrome caused by serotonin-secreting tumors, a test is carried out for the content in the urine of the product of the vital activity of the tumor - 5-hydroxyindoleacetic acid (5-HIAA). To exclude a false positive result, the patient is prohibited three days before the test from taking foods that contain serotonin (tomatoes, pineapples, bananas, avocados, plums, walnuts, eggplants, and other foods) as well as drugs that contain it.

Treatment

For treatment, medications are prescribed that suppress the production of hormones by a neuroendocrine tumor or reduce their effect. Some symptoms, such as hot flashes, can be treated with somatostatin drugs (octreotide). In addition, hot flashes can be combated with phenothiazines (chlorpromazine), phentolamines.

Diarrhea can be treated with loperamide, diphenoxylate. To prevent pellagra, a meal rich in vitamin PP is prescribed, as well as a synthetic analogue of the vitamin.

To prevent the conversion of 5-hydroxytryptophan to serotonin, patients are prescribed methyldopa or phenoxybenzamine.

Information about octreotide, loperamide and other medicines can be found in the electronic guide

History reference: 1868 - Lanhans first described a carcinoid tumor; 1907 - Oberndofer first used the term "carcinoid"; 1930 - Cassidy described a disease accompanied by watery diarrhea, heart failure, shortness of breath, redness of the skin of the face; 1931 - Scholte was the first to suggest a connection between a tumor of the small intestine and damage to the valves of the valves of the right half of the heart; 1949 - Rapport proposed a structural formula for serotonin; 1952 - Bjork, Aksen, Thorson first described the clinical manifestations of carcinoid syndrome in a boy who suffered from stenosis of the opening of the pulmonary valves, insufficiency of the tricuspid valve and unusual cyanosis; 1954 - Waldenstrem and Pernov discovered hyperserotoninemia in patients with metastatic carcinoid.; 1960 - Harris observed a persistent hypertensive response when serotonin was administered to a human.

Carcinoid syndrome- 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 development of carcinoid syndrome is due to a hormonally active tumor originating from enterochromaffin (argentaffin) intestinal cells (Kulchitsky cells). At the same time, increasing intestinal disorders are accompanied by hypertensive syndrome (Gogin E.E., 1991).

Until 1953, each case of detection of carcinoid syndrome was considered as casuistic. However, since the description of the clinical picture of the disease, the incidence of carcinoid tumors has increased significantly. However, intravital diagnosis of carcinoid syndrome is quite rare. According to autopsy materials, carcinoids occur in 0.14–0.15% of cases.

Most often, carcinoid tumors are localized in the gastrointestinal tract, less often they occur in the bronchi, gall bladder, pancreas and ovaries. The sizes of tumors, as a rule, are not large and vary from 0.1 to 3 cm. The kacinoid cell is polygonal, has chromatin and a large number of randomly arranged granules. The connective tissue stroma of a carcinoid tumor contains a significant number of mast cells that have the ability to concentrate and possibly produce serotonin.

At the basis of pathogenesis carcinoid syndrome is the production of 5-hydroxytryptamine (serotonin, enteramine) by tumor cells, which causes hyperserotoninemia and an excess of other physiologically active substances. The classic symptoms of carcinoid syndrome with a significant increase in blood pressure develop only when the primary focus or tumor metastases are outside the hepatic barrier. In these cases, the serotonin formed by the tumor cells is not destroyed and enters the general circulation through the hepatic vein, causing various pathological conditions.

The vasoconstrictive action of serotonin was its first property to be known. Most researchers have found a hypertensive reaction when serotonin is administered to a person. However, there is a sufficient number of studies indicating that after giving serotonin, there is a decrease in blood pressure. The nature of the vascular response in response to serotonin is affected by the method of its administration. So, with intravenous administration, an increase in minute volume and blood pressure is observed, and with the introduction of serotonin intraperitoneally, a hypotensive reaction is noted. There is an opinion that the variability of blood pressure responses to serotonin is associated with the ability of the vascular bed to respond differently to this amine.

Close interactions are known to exist between serotonin and other biological amines. For example, it is considered proven that the development of vascular disorders in carcinoid syndrome is due to the interaction of serotonin and catecholamines (Menshikov VV et al., 1972). Cases of combination of carcinoid syndrome with acromegaly and hypercortisolism are described. It is possible that this combination is due to the ability of carcinoid tumor cells to produce GH- and ACTH-like substances.

Under the influence of high concentrations of serotonin fibrosis of the endothelial tissue develops, smooth muscle contraction occurs, which causes narrowing of the arteries. The defeat of the cardiovascular system due to hyperserotoninemia in carcinoid syndrome is reduced to the development of tricuspid valve insufficiency and pulmonary artery stenosis, as well as fibrosis of the endocardium of the right atrium and right ventricle. Narrowing of the arterioles leads to the development of arterial hypertension.

Carcinoid tumors are classified as arising from anterior intestinal tube(bronchi, stomach, duodenum, bile ducts, pancreas), middle part of intestinal tube(jejunum and ileum, appendix, ascending colon) back of intestinal tube(transverse colon, descending, sigmoid and rectum). Sometimes they are also found in the gonads, prostate, kidneys, mammary glands, thymus, or skin.

For the clinical picture Carcinoid syndrome is characterized by the presence of vasomotor disorders of the type of "tides". At the same time, certain areas of the skin become red, sometimes cyanotic, the patient feels heat in these places. In addition to violations of vascular tone and heart damage, there is a pronounced abdominal syndrome, which is manifested by the presence of diarrhea, pain along the intestines. The influence of serotonin on the smooth muscles of the bronchi can lead to a sharp narrowing of the latter and the development of asthma attacks. As a rule, the course of the disease is paroxysmal. The duration of the attacks varies considerably - from 30 seconds to 10 minutes, and in some cases the attacks can be repeated several times during the day. Their occurrence is most often provoked in connection with nervous or physical stress, alcohol intake. A number of symptoms, such as cyanosis, telangiectasia, oliguria, and heart damage, persist for a long time and determine the condition of patients in the interictal period.

The most characteristic changes in the blood picture with carcinoid syndrome, there is an acceleration of ESR and leukocytosis, and a direct relationship is determined between changes in the blood and the occurrence of crises. Carcinoids, especially bronchial ones, can secrete ACTH, which causes Cushing's syndrome, a growth hormone-releasing hormone that causes acromegaly.

The diagnosis is confirmed 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, lungs during instrumental research methods. Biochemical indicators 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. Definition 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.

Complex topical diagnostics carcinoids involves 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 whole 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.

Considering the general principles of therapy 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 impossible for some 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 medications, used in the treatment of carcinoid tumors, cyclophosphamide should be distinguished, 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 that produce mainly 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.

Numerous studies have been conducted on the use of a-interferon in patients with carcinoid tumors. For the treatment of patients, doses of a-interferon 3-9 IU were used 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 carried out according to 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.