Carcinoid syndrome

Carcinoid syndrome develops only in some patients with carcinoid tumors and is characterized by a peculiar reddening of the skin ("hot flashes"), abdominal colic, spasms and diarrhea. After several years, right heart valve insufficiency may develop. The syndrome develops as a result of the action of vasoactive substances secreted by tumor cells (including serotonin, bradykinin, histamine, prostaglandins, polypeptide hormones); the tumor is usually metastatic.

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Causes carcinoid syndrome

Endocrinologically active tumors from the diffuse peripheral endocrine or paracrine systems produce various amines and polypeptides, the action of which is manifested by certain clinical symptoms and signs, which together constitute the carcinoid syndrome.

Carcinoid syndrome usually results from endocrinologically active tumors that develop from neuroendocrine cells (mostly in the ileum) and produce serotonin. However, these tumors can also develop in other parts of the gastrointestinal tract (especially in the appendix and rectum), pancreas, bronchi, or, less commonly, in the gonads. Rarely, certain highly malignant neoplasms (e.g., small cell lung carcinoma, islet cell carcinoma of the pancreas, medullary thyroid carcinoma) are responsible for the syndrome. Carcinoid tumors located in the intestine usually do not give clinical signs of carcinoid syndrome until metastases to the liver develop, because the products of tumor metabolism are rapidly destroyed in the blood and liver by liver enzymes in the portal circulation system (for example, serotonin is destroyed by hepatic monoamine oxidase).

Liver metastasis results in the release of tumor metabolic products through the hepatic veins directly into the systemic circulation. Metabolic products released by carcinoid tumors primarily localized in the lungs and ovaries bypass the portal vein system and can therefore induce the development of similar clinical symptoms. Rarely, intestinal carcinoid tumors, with intra-abdominal spread only, can directly release active substances into the general circulation or lymphatic system, causing the development of clinical symptoms.

The action of serotonin on smooth muscles results in the development of diarrhea syndrome, intestinal colic and malabsorption. Histamine and bradykinin, due to their vasodilatory effects, cause hyperemia of the skin of the face and the development of characteristic "hot flashes". The role of prostaglandins and various polypeptide hormones produced by paracrine cells is still unknown; these issues await further research. Sometimes the development of carcinoid tumors may be accompanied by elevated levels of human chorionic gonadotropin and pancreatic polypeptides.

Many patients develop right-sided endocardial fibrosis, leading to pulmonary artery stenosis and tricuspid valve regurgitation. Left ventricular involvement, which may be seen in bronchial carcinomas, is quite rare because serotonin is destroyed during its passage through the lungs.

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Symptoms carcinoid syndrome

The most common (and often earliest) symptom of carcinodyne syndrome is discomfort associated with the development of characteristic "flushes" in typical locations (head and neck), often preceded by emotional stress or heavy meals, hot drinks, or alcohol. Striking changes in skin color may occur, ranging from mild pallor or erythema to a violet hue. Gastrointestinal spasms with the development of recurrent diarrhea are quite common and constitute the main complaints of patients. Malabsorption syndrome may occur. Patients who have developed valvular heart disease may have heart murmurs. Asthmatic breathing, decreased libido, and erectile dysfunction may be observed in some patients; pellagra develops rarely.

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Diagnostics carcinoid syndrome

Serotonin-secreting carcinomas are diagnosed based on the presence of a classic clinical symptom complex. The diagnosis is confirmed by detecting increased urinary excretion of the tumor metabolism product 5-hydroxyindoleacetic acid (5-HIAA). To avoid a false-positive result in a laboratory study, the analysis is performed under the condition that serotonin-containing products (such as bananas, tomatoes, plums, avocados, pineapple, eggplants, walnuts) are excluded from the patient's diet 3 days before the study. Some medications containing guaifenesin, metacarbamol, phenothiazides may also distort the test results, so they should be discontinued in advance of the study. On the third day, a 24-hour urine portion is collected for the test. Normally, urinary excretion of 5-HIAA is less than 10 mg / day (< 52 μmol / day); In patients with carcinoid syndrome, excretion is usually greater than 50 mg/day (> 250 μmol/day).

Provocative tests with calcium gluconate, catecholamines, pentagastrin, or alcohol are used to induce flushes. These tests may be useful diagnostically when the diagnosis is in doubt, but should be used with great caution. Noninvasive modern techniques are available to localize nonfunctioning carcinomas, although invasive diagnostic intervention, sometimes including laparotomy, may be required. Scanning with radiolabeled somatostatin receptor ligands 1111-p-pentetreotide or 123-meta-iodobenzylguanine can detect metastases.

Other conditions that may cause the typical clinical picture of hot flushes but may not be related to the carcinoid syndrome should be excluded. In patients who do not have increased urinary 5-HIAA excretion, disorders involving systemic mast cell activation (eg, systemic mastocytosis with increased urinary histamine metabolites and increased serum tryptase) and idiopathic anaphylaxis may cause a similar clinical syndrome. Additional causes of hot flushes include menopausal syndrome, ingestion of ethanol-containing products and medications such as niacin, and certain tumors (eg, vipomas, renal cell carcinomas, medullary thyroid carcinomas).

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Treatment carcinoid syndrome

Some symptoms, including hot flashes, are reduced by somatostatin (which inhibits the secretion of most hormones), but without reducing the excretion of 5HIAA or gastrin. Numerous clinical studies have shown good results in the treatment of carcinoid syndrome using octreotide, a long-acting somatostatin analogue. Octreotide is the drug of choice for the treatment of symptoms such as diarrhea and hot flashes. Based on clinical assessments, tamoxifen is not always effective; the use of leukocyte interferon (IFN) reduces clinical manifestations.

Flushing may also be successfully treated with phenothiazines (eg, prochlorperazine 5 to 10 mg or chlorpromazine 25 to 50 mg orally every 6 hours). Histamine receptor blockers may also be used in therapy. Phentolamine 5 to 10 mg intravenously prevented the development of experimentally induced "flushing". Glucocorticoids (eg, prednisolone 5 mg orally every 6 hours) may be useful in cases of severe "flushing" caused by bronchial carcinoma.

The diarrhea syndrome can be successfully treated with codeine phosphate (15 mg orally every 6 hours), opium tincture (0.6 ml orally every 6 hours), loperamide (4 mg orally as a loading dose and 2 mg after each bowel movement; maximum to 16 mg daily), diphenoxylate 5 mg orally every other day, or peripheral serotonin antagonists such as cyproheptadine 4 to 8 mg orally every 6 hours or methysergide 1 to 2 mg orally 4 times daily.

Niacin and adequate protein intake are prescribed to prevent the development of pellagra, since dietary tryptophan is a competitive inhibitor of serotonin secreted by the tumor (reducing its effect). Enzyme inhibitors that prevent the conversion of 5-hydroxytryptophan to serotonin are prescribed, such as methyldopa (250-500 mg orally every 6 hours) and phenoxybenzamine (10 mg daily).

Forecast

Despite the obvious metastasis of this category of tumors, they nevertheless grow slowly, and the survival period of such patients who have carcinoid syndrome - 10-15 years - is not unusual. Repeated surgical treatment of primary pulmonary carcinoid tumors is often successful. For patients with metastases to the liver, surgical intervention is indicated only for diagnostic purposes or only as a palliative. There is no (according to the literature) effectiveness of chemotherapeutic treatment, although therapy with streptozocin with 5-fluorouracil and sometimes doxorubicin has found wide application in clinical practice.

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