Carcinoid syndrome is a complex of symptoms resulting from hormonal activity of tumors from the cells of the APUD system. It includes hot flashes, persistent diarrhea, fibrous lesion of the right half of the heart, abdominal pain and bronchospasm. During surgical interventions, the development of a life-threatening carcinoid crisis is possible. Pathology 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.
ICD 10
E34.0 Carcinoid syndrome
General information
Carcinoid syndrome is a symptom complex observed in potentially malignant slow–growing neuroendocrine tumors that can occur in almost any organs. In 39% of cases, neoplasms provoking 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, in 2-3% – in the pancreas, in 1% – in liver and 10% – in the bronchi. In 20% of cases, gastrointestinal carcinoid tumors are combined with other neoplasms of the large intestine. Pathology usually develops at the age of 50-60 years, men and women suffer equally often.
Carcinoid was first described at the end of the XIX century. In the 50s of the last century, a group of researchers led by Waldenstrom compiled an expanded description of the histological and histochemical features of carcinoid tumors, and also proved the connection between such neoplasms and the development of this syndrome. For a long time, carcinoids were considered as benign tumors, but recent studies have shaken this point of 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
The cause of the development of carcinoid syndrome is the hormonal activity of tumors originating from neuroendocrine cells of the APUD system. Symptoms are determined by changes in the level of various hormones in the patient’s blood. Usually such neoplasms secrete a large amount 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 flow directly into the general bloodstream through the hepatic veins, without undergoing cleavage in liver cells.
With carcinoids localized in the lungs, bronchi, ovaries, pancreas and other organs, carcinoid syndrome can develop before metastasis begins, since blood from these organs does not pass through the portal vein system before entering the systemic circulation and is not “cleaned” in liver tissue. Clearly 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 cardiac pathology. As a rule, with carcinoid syndrome, fibrous degeneration of the endocardium of the right half of the heart is observed. The left half of the heart is rarely affected, since serotonin is destroyed when 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 clarified.
Carcinoid syndrome symptoms
The most common manifestation of carcinoid syndrome is hot flashes. This symptom is observed in 90% of patients. There is a sudden, periodic, paroxysmal redness of the upper half of the trunk. Usually hyperemia is especially pronounced in the face, nape and neck. Patients with carcinoid syndrome complain of a feeling of heat, numbness and burning. Hot flashes are accompanied by increased heart rate and a drop in blood pressure. Dizziness may occur due to deterioration of blood supply to the brain. During seizures, redness of the sclera and lacrimation may occur.
At 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. Usually seizures occur against the background of alcohol consumption, spicy, fatty and spicy foods, physical exertion, psychological stress or taking medications that increase serotonin levels. Less often, tides develop spontaneously, for no apparent reason.
Diarrhea is detected in 75% of patients with carcinoid syndrome. 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 disrupted, hypovitaminosis develops. With long-term ongoing carcinoid syndrome, drowsiness, muscle weakness, fatigue, thirst, dry skin and weight loss are noted. In severe cases, edema, osteomalacia, anemia and pronounced trophic changes of the skin due to gross metabolic disorders occur.
Cardiac pathology is found in half of patients suffering from carcinoid syndrome. As a rule, endocardial fibrosis is detected, accompanied by a lesion of the right half of the heart. Fibrous changes cause the failure of the tricuspid and pulmonary valves and provoke stenosis of the pulmonary trunk. Valve failure and pulmonary artery stenosis in carcinoid syndrome can lead to the development of heart failure and stagnation in the large circle of blood circulation, which are manifested by edema of the lower extremities, ascites, pain in the right hypochondrium due to liver enlargement, swelling and pulsation of neck veins.
Bronchospasm phenomena are observed in 10% of patients with carcinoid syndrome. Patients are concerned about attacks of expiratory shortness of breath, accompanied by whistling and buzzing wheezes. Another fairly common manifestation of carcinoid syndrome is abdominal pain, which may be caused by a mechanical obstacle to the movement of intestinal contents due to the growth of a primary tumor or the appearance of secondary foci in the abdominal cavity.
A formidable 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 occurred during a carcinoid crisis poses an immediate threat to the patient’s life and can lead to a fatal outcome.
Diagnostics
The diagnosis is made by an oncologist on the basis of characteristic symptoms, external examination data and objective studies. Elevated levels of serotonin are detected in the blood plasma. A high content of 5-hydroxyindolacetic acid is detected in the urine. To exclude a false positive result, it is recommended to refrain from taking products containing a large amount of serotonin (walnuts, eggplants, avocados, tomatoes, bananas, etc.) and some medications within 3 days before the tests are given to a patient with suspected carcinoid syndrome.
In doubtful cases, tests with alcohol, catecholamines or calcium gluconate are carried out to stimulate hot flashes. To determine the localization of the tumor and detect metastases, a patient with carcinoid syndrome is referred for CT and MRI of internal organs, scintigraphy, radiography, gastroscopy, colonoscopy, bronchoscopy and other studies. If there are sufficient indications, laparoscopy can be used. Carcinoid syndrome is differentiated with systemic mastocytosis, hot flashes during menopause and side effects when taking certain medications.
Treatment
The main method of treatment is surgical intervention. Depending on the localization and prevalence of the process, radical excision of the primary focus or various palliative operations are possible. In case of carcinoid syndrome caused by tumors of the small intestine, resection of the small intestine is usually performed together with the mesentery area. In case of damage to the large intestine and neoplasms located in the area of the ileocecal sphincter, right-sided hemicolectomy is performed.
In case of carcinoid syndrome caused by a neoplasm in the appendix, an appendectomy is performed. Some oncologists additionally remove nearby lymph nodes. Palliative surgical interventions are indicated at the stage of metastasis, involve 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 carcinoid syndrome is embolization or ligation of the hepatic artery.
The indication for chemotherapy for carcinoid syndrome is the presence of metastases. In addition, this method of treatment is used in the postoperative period for heart damage, liver dysfunction and high levels of 5-hydroxyindolacetic acid in the urine. To avoid the development of a carcinoid crisis, treatment begins with small doses of drugs, gradually increasing the dosage. The effectiveness of chemotherapy for carcinoid syndrome is low. Significant improvement is observed in no more than 30% of patients, the average duration of remission is 4-7 months.
As symptomatic therapy for carcinoid syndrome, serotonin antagonist drugs are prescribed: fluoxetine, sertraline, paroxetine, etc. In tumors producing 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 area and can significantly reduce the manifestations of this syndrome in more than half of patients.
The prognosis is determined by the prevalence and degree of malignancy of the tumor. With radical removal of the primary focus and the absence of metastases, complete recovery is possible. With metastasis, the prognosis worsens. Due to the slow progression of the carcinoid, the 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.