Symptoms
The main symptoms are diarrhea with watery stools, cramps in the lower abdomen, and flushing, which is seizure-like severe facial redness or purplishness, although the neck or legs may also be affected. The untreated or undiagnosed disease can lead to valvular heart defect, telangiectasias, and pellagra (vitamin B2 deficiency).
Causes
Carcinoid syndrome is based on the tumor of the same name, which was discovered by Oberndorfer in 1907. It can affect any neuroendocrine tissue but most commonly occurs in the stomach, colon, appendix, or lungs. They are tumors with characteristic appearance and staining behavior. They may develop, for example, in patients with hypergastrinemia, i.e., increased gastrin secretion into the blood, in the course of Zollinger-Ellison syndrome. Often there is excessive serotonin release from the degenerated neuroendocrine cells, so that liver function may be affected. Monoamine oxidase (MAO), localized in liver cells, catalyzes the degradation of serotonin released by the tumor to biologically inactive 5-hydroxyindoleacetoacetic acid (5-HIAA). Urine 5-HIAA concentration is used for definitive diagnosis in combination with imaging techniques.
Risk factors
Diseases of the gastrointestinal tract, such as Zollinger-Ellison syndrome, are a risk factor. Black Africans also have an increased risk of disease for the forms with intestinal involvement compared with other ethnic groups. An epidemiologic study from Sweden cited carcinoid cases in first-degree relatives, a high level of education, and birth in a large city as risk factors.
Diagnosis
The diagnosis is often made very late, because only then do the typical symptoms become apparent. One primarily uses the 5-HIAA urine test, for which threshold values are defined. Diagnostically, imaging techniques such as sonography, tissue sampling and histological staining are also used. Differential diagnosis: Enzyme or other defects in the neurotransmitter cycle of histamine and serotonin, such as histamine intolerance or migraine. Other diseases of the hormone-forming system, such as Cushing’s disease or a pheochromocytoma.
Drug therapy
Chemoembolization:
- Chemoembolization is a combination of surgical intervention and chemotherapy used primarily paliatively for liver metastasis. For this purpose, a catheter is placed in the hepatic artery or portal vein and a cytostatic drug and an embolization material, such as Spherex, are administered. In this way, the vessel is blocked and the local cytostatic administration via the catheter can reach surrounding tumor tissue in a highly concentrated form. The usual premedication is necessary for this: Opioids, glucocorticoids and antiemetics.
Somatostatin analogues:
- Alternatively, somatostatin analogues are used, which the patient can inject subcutaneously himself. Here, the two synthetic oligopeptides octreotide and lanreotide are available. Lanreotide is given every 28 days. The somatostatin analogues block the effects of peptide hormones released by the primary tumor, e.g. tachykinins such as bradykinin. Thus, in many patients, the very unpleasant and socially debilitating flush can be blocked. Especially in chemoembolization, somatostatin analogues should be given before the procedure to avoid massive release of serotonin and peptide hormones with vasospasm, which can lead to death of the patient during the procedure.
- Administration of radiolabeled somatostinal analogues (111In-pentetreotide) represents another new therapeutic approach. However, this selective radiotherapy requires isolation of patients because of the large radiation dose, which is too risky for the surrounding environment.
Serotonin antagonists:
- Ketanserin and methysergide have been used to control symptoms. Both serotonin receptor antagonists appear useful for symptom blockade. However, ketanserin also has an antihypertensive effect, which may lead to adverse effects. In many countries, both are unavailable or available only as veterinary medications. The 5-HT3 antagonist ondansetron, approved for cytostatic-induced vomiting, is being evaluated in clinical trials for symptom control in carcinoid. Important symptomatic therapeutics include the somatostatin analogues already discussed.
Prevention
The early clarification of gastrointestinal symptoms seems particularly useful, otherwise tumor prophylaxis is difficult. With a diagnosis of carcinoid syndrome, the affected person should try to control symptoms if possible; this can be done, for example, by avoiding vigorous exercise, alcohol consumption, and highly spiced exotic foods. Non-specific warning symptoms include recurrent watery diarrhea and, in rare cases, persistent cough (carcinoid of the bronchi). Flushing is a typical warning symptom. For carcinoid patients, supplementation with vitamin B2 (nicotinamide) is recommended to counteract deficiency symptoms due to excessive serotonin formation, which is vitamin B2 dependent.
