A carcinoid syndrome develops in some patients with a carcinoid tumor and is characterized by a flushing of the skin, abdominal cramps and diarrhea. After a few years, a right-sided valvular heart disease may show. The syndrome is caused by vasoactive substances (including serotonin, bradykinin, histamine, prostaglandins and polypeptide hormones), which are secreted by the tumor, which is typically a metastatic intestinal carcinoid. The diagnosis is made clinically and by the detection of 5-HIAA in the urine. For tumor localization scintigraphy or laparotomy is sometimes necessary. Chemotherapy can be performed in malignant tumors. Treating the symptoms is done with the somatostatin analogue octreotide, but where it is possible is performed surgical removal.
A carcinoid syndrome develops in some patients with a carcinoid tumor and is characterized by a flushing of the skin, abdominal cramps and diarrhea. After a few years, a right-sided valvular heart disease may show. The syndrome is caused by vasoactive substances (including serotonin, bradykinin, histamine, prostaglandins and polypeptide hormones), which are secreted by the tumor, which is typically a metastatic intestinal carcinoid. The diagnosis is made clinically and by the detection of 5-HIAA in the urine. For tumor localization scintigraphy or laparotomy is sometimes necessary. Chemotherapy can be performed in malignant tumors. Treating the symptoms is done with the somatostatin analogue octreotide, but where it is possible is performed surgical removal. Etiology Endocrine active tumors of the peripheral endocrine or paracrine system produce various amines and polypeptides with associated symptoms and clinical signs. This includes the carcinoid syndrome. A carcinoid syndrome is usually formed by a endocrinologically active malignant tumor of neuroendocrine cells (mostly in the ileum), the serotonin secreted. It can also be as a result of other tumors of the gastrointestinal tract caused (especially by tumors of the appendix and rectum), pancreas, bronchi and rarely also the gonads. Very rarely, certain highly malignant tumors (eg. As the small cell lung cancer, the islet cell carcinoma of the pancreas or medullary thyroid carcinoma) are responsible. An intestinal carcinoid usually causes only symptoms of the syndrome when liver metastases have formed because the metabolically active products of the tumor are rapidly destroyed by enzymes in the blood or in the liver during portal passage (z. B. is serotonin by monoamine oxidase in the liver reduced). However, hepatic metastases secrete metabolically active products via the hepatic veins directly into the systemic circulation. Metabolically active products of primary pulmonary or ovarian carcinoids bypass the portal vein and can cause similar symptoms. Very rarely, cause intestinal carcinoid tumors that spread only intra-abdominal symptoms when they secrete their products directly into the systemic circulation or lymphatic vessels. Pathophysiology Serotonin acts on smooth muscle cells, causing diarrhea, colic and malabsorption. Histamine and bradykinin produce a condition called Flushing through their vasodilating properties. Elevated levels of human chorionic gonadotropin and polypeptides of the pancreas can also be found in carcinoids. The role of prostaglandins and other polypeptide hormones that can be produced by paracrine cells needs further research. Some patients develop a preference right-sided endocardial fibrosis, which can lead to a pulmonary valve and a tricuspid regurgitation. Changes in the left heart, as described in bronchial carcinoid tumors are rare because serotonin is released during the lung passage. Symptoms and signs The most common (and often earliest) sign is unpleasant flushing, typically of the head and neck blush is often triggered by emotional stress, food, hot drinks or alcohol. It occurs striking changes in skin color that can range over a redness to a purple hue of pallor. In addition, abdominal cramps occur with recurrent diarrhea that cause the patient the most violent complaints. Malabsorption can also be observed. Patients with heart valve defects can be noticed by a heart murmur. Some patients have asthmatic symptoms, reduced libido and erectile dysfunction. Pellagra rarely develops. Diagnosis 5-HIAA (5-HIAA) in urine The diagnosis serotonin secreting carcinoid can often be made solely on the basis of symptoms and clinical signs. The diagnosis is confirmed when an evidence of increased excretion of serotonin metabolite 5-HIAA may be provided in the urine. To avoid false positive results, the doctors perform the measurement only after when the patient for at least 3 days of serotonin-containing foods (eg. As bananas, tomatoes, plums, avocados, pineapples, eggplant and walnuts) has been excluded. Certain medications, such. As guaifenesin, methocarbamol, and phenothiazines, also affect the test and should be temporarily discontinued. On the 3rd day, a 24-hour urine is collected. The normal excretion of 5-HIAA is <10 mg / day (<52 .mu.mol / day); in patients with carcinoid syndrome excretion is> 50 mg / d (> 260 .mu.mol / day). In the past, provocation tests were performed using calcium gluconate, catecholamines, pentagastrin or alcohol, to produce a Flushing. Although these tests can be helpful if there are still about the diagnosis doubt they are rarely used and must be done very carefully. Localization of the tumor, the location of the tumor includes angiography, CT or MRI, the same techniques used to locate a nonfunctional carcinoid. Localization can require extensive evaluation, sometimes laparotomy. Scintigraphy with the radionuclide-labeled somatostatin receptor 111 In Inpentetreotide or with iodine-123-metaiodobenzylguanidine may metastases identifizieren.Ausschluss other causes of Flushing Other diseases associated with a Flushing and therefore can be confused with a carcinoid tumor, should be excluded. In patients in which the 5-HIAA excretion is not increased, disorders that affect the systemic activation of mastocytes (z. B. systemic mastocytosis with elevated urine levels of histamine metabolites and elevated serum tryptase levels), and idiopathic anaphylaxis for a can Flushing to be responsible. Other causes were the menopause, ethanol poisoning, drugs such. As niacin, and certain other tumors (z. B. VIPomas, renal cell carcinoma, medullary thyroid carcinoma). Prognosis The prognosis depends on the primary localization, the severity and stage. Apart from metastatic forms of the disease, these tumors are more likely to slow growth, and survival of 10-15 years is not uncommon. Therapy Surgical resection Surgical resection octreotide in symptoms Resection primary Lungenkarzinoide is often curative. In patients with liver metastases, surgical compression can alleviate the symptoms, although it is not curative; in some cases it can increase survival. Moreover, locoregional therapies against liver metastases trans-arterial chemoembolization can (TACE) include mild embolization radioembolisation with Yttrium-90 microspheres and radiofrequency ablation. Radiotherapy remains, among other things because of the high radiosensitivity of healthy liver tissue, without success. Yet no effective regime for chemotherapy is really established, but streptozocin with 5-fluorouracil is also used in combination with doxorubicin verwendet.Linderung symptoms Certain symptoms, including the Flushing with octreotide can (which inhibits the secretion of most hormones) can be mitigated , The values ??for 5-HIAA in the urine or gastrin are unaffected. Countless studies have shown good results for octreotide, a long-acting somatostatin analogue. Octreotide is the drug of choice to get diarrhea and flushing under control. Case reports show that tamoxifen is sometimes effective and leukocytic interferon (IFN-?) temporarily the symptoms improved. Flushing can also phenothiazines (eg. B. 5-10 mg prochlorperazine or chlorpromazine 25-50 mg p.o. every 6 h) can be treated. Similarly, one can use histamine type 2 (H2) blockers. Phentolamine (an alpha blockers) 5-15 mg i.v. could prevent experimentally induced Flushing. Corticosteroids (e.g., prednisone 5 mg p.o. every 6 h) can be in terms of bronchial obstruction of benefit in heavy Flushing, which is caused by a bronchial carcinoid. Diarrhea can with codeine 15 mg p.o. every 4-6 h, tincture of opium 0.6 ml p.o. every 6 h, loperamide 4 mg p.o. p.o. as an initial dose and then 2 mg after each liquid stool up to a total dose of 16 mg / day, diphenoxylate 5 mg 4 times a day or peripheral serotonin antagonists such as cyproheptadine 4-8 mg po every 6 h to be treated. Niacin and adequate protein intake are needed to prevent pellagra, as it is converted into serotonin in the diet recorded tryptophan from the tumor. To enzyme inhibitors, which prevent the conversion of 5-hydroxytryptophan in serotonin, belongs methyldopa (250-500 mg p.o. every 6 h). Summary Only some carcinoid tumors secrete substances that cause carcinoid syndrome. The main cause substances serotonin, leading to, abdominal cramps and diarrhea leads and histamine, which causes reddening. The diagnosis is made by detecting the serotonin metabolite 5-HIAA. Octreotide can help to control the symptoms. In the absence of metastases surgical resection may be curative. A surgical compression can ease in patients with liver metastases, symptoms and may prolong survival.