Neuroendocrine tumors (NET) - or neuroendocrine neoplasms (NEN) according to the current WHO classification - represent a complex group of rare but increasingly common tumors. They arise from cells of the neuroendocrine system. As these cells are diffusely distributed throughout the body, neuroendocrine tumors can occur at many sites both inside and outside the gastrointestinal tract. A special feature of neuroendocrine tumors (NET) is their ability to produce and release hormones. The uncontrolled release of hormones can lead to characteristic syndromes (carcinoid syndrome, insulinoma, gastrinoma = Zollinger Ellison syndrome, VIPoma = Verner-Morrison syndrome, glucagonoma syndrome, etc.), but the majority of patients do not suffer from hormone syndromes, i.e. their tumor disease is not functionally active. The most common sites of origin of gastrointestinal tumors are the rectum (usually small and without metastasis), the pancreas and the small intestine. Metastases (secondary tumors) are often already present at the time of diagnosis.

In the context of multiple endocrine neoplasia (MEN) type I, pancreatic neuroendocrine tumors can also be associated with other tumors of the endocrine system.

Carcinoid syndrome refers to the occurrence of the following symptoms: Seizure-like occurrence of hot flushes, which mainly affect the head and neck and are triggered by certain foods such as cheese, physical and psychological stress or alcohol. In addition, there is usually watery diarrhea, sometimes accompanied by abdominal pain. In the further course of the disease, carcinoid syndrome can lead to carcinoid heart disease. This prognostically relevant complication, also known as Hedinger's syndrome, corresponds to endocardial fibrosis (thickening of the inner lining of the heart due to increased connective tissue formation), which mainly affects the right heart. The most frequent manifestation is tricuspid valve insufficiency (leakage of the valve between the right atrium and right ventricle), followed by pulmonary valve stenosis (insufficient opening of the valve between the right ventricle and pulmonary artery) and a combined heart valve defect. If left untreated, it usually leads to heart failure. Other symptoms may include telangiectasia (vasodilatation of the skin, approx. 25% of those affected), asthmatic complaints (approx. 15% of those affected) or pellagra-like skin changes (inflammatory skin changes with hyperpigmentation in vitamin B2 deficiency; rare). Most tumors associated with carcinoid syndrome are located in the small intestine and in at least 90% of cases already have liver metastases when carcinoid syndrome occurs. The cause of carcinoid syndrome is the release of serotonin and other substances such as tachykinins and prostaglandins by the tumor cells. Diagnostics: As the measurement of serotonin in the blood is susceptible to interference, the determination of the serotonin degradation product 5-hydroxyindoleacetic acid (5-HIES) in acidified urine is recommended for diagnostic purposes. Care should be taken to avoid certain serotonin-rich foods that could falsify the result.

Gastrin causes the production of gastric acid. Gastrinomas are clinically manifested by Zollinger-Ellison syndrome consisting of abdominal pain due to recurrent ulcers in the duodenum, stomach and occasionally in the deeper small intestine, heartburn, nausea and diarrhea. Gastrinomas are mainly localized in the duodenum and pancreas. In a quarter of cases, they are hereditary (MEN-1 syndrome = multiple endocrine neoplasia type 1) and are associated with the occurrence of hormone-producing tumors in various organs such as the parathyroid gland, pituitary gland and pancreas. Diagnostics: Fasting level of gastrin in the blood. For this, proton pump inhibitors such as pantoprazole or omeprazole should be discontinued for at least one week. If this does not give a clear indication of a gastrinoma, a so-called secretin test is carried out.

These most common hormone-active tumors of the pancreas produce insulin and cause typical symptoms of hypoglycemia with cold sweats and tremors when a blood sugar level of 50 mg/dl is detected and rapid improvement after sugar intake. Insulinomas are usually small, occur singly and are benign in over 90% of cases. They occur almost exclusively in the pancreas and can rarely be part of the hereditary MEN-1 syndrome. Diagnosis: 72-hour starvation test with regular measurement of blood glucose, C-peptide and insulin in the blood.

Glucagonomas are glucagon-producing tumors that also occur in >90% of cases in the pancreas. Clinical manifestations include diabetes, weight loss, anemia, diarrhea, a tendency to thrombosis and a characteristic skin rash with blistering (so-called erythema necrolyticum migrans), which mainly occurs in the flexural folds, on the lower leg, around the mouth and in the genital region. Glucagonomas are already large tumors at the time of diagnosis and 2/3 of cases have already metastasized. Diagnosis: plasma glucagon, with a level of 1000ng/ml being considered conclusive.

These VIP-producing tumors, also known as Verner-Morrison syndrome or "pancreatic cholera", are characterized by large-volume (6-8 l/day) diarrhea with loss of blood salts and fluid. 90% of VIPomas are located in the pancreas. In about half of the cases, metastases are already present at the time of diagnosis. Diagnosis: secretory diarrhea with elevated plasma VIP levels.