Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0016382 (flushing)
 6,387 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Malignant carcinoid syndrome is characterized most commonly by flushing and diarrhea of varying severity when tumors metastasize to the liver. Besides supportive measures for mild symptoms, the pharmacological management includes drugs to inhibit synthesis, release or peripheral actions of the circulating tumor products either alone or in combination. Among those agents octreotide, a synthetic long-acting analogue of somatostatin, is the drug of choice because it has proved useful for ameliorating symptoms in most patients with this syndrome. Although there is a multitude of potential and actual side effects, this antihormonal drug is very well tolerated and is a significant advance in therapy.
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PMID:Therapeutic principles in the management of metastasising carcinoid tumors: drugs for symptomatic treatment. 769 39

Carcinoid tumors stimulate the release of specific hormones that lead to flushing, diarrhea, and bronchospasm. Serotonin is the most significant of these substances. Recently, a somatostatin analogue as well as the longer acting octreotide have been used to inhibit tumor secretions and reduce their untoward actions. This is a case report in which somatostatin was used perioperatively for removal of carcinoid tumors with an uneventful course.
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PMID:Carcinoid syndrome. 790 89

Octreotide is a synthetic octapeptide somatostatin analogue which has higher potency and longer duration of action than the natural hormone. It is effective after subcutaneous administration and no rebound hypersecretion has been observed. Pharmacological effects of octreotide include inhibition of numerous hormones (growth hormone, TSH, insulin, glucagon and all gut hormones), of exocrine secretion (gastric acid, pancreatic enzyme), and of small-bowel absorption. This review deals with clinical application of octreotide in endocrine disorder. In patients with acromegaly octreotide treatment results in decrease of growth hormone (GH) and IGF-I together with tumour shrinkage and clinical improvement. Although variability in response to treatment is obvious for majority of patients the most effective dose is 100 mcg three times daily subcutaneously. Normalization of GH levels could be achieved in more than 50% of treated patients. It has also been shown that octreotide could be effective in TSH secreting pituitary adenoma, ACTH secreting adenoma as well as in non-secretory pituitary tumours. A marked biochemical and clinical responses together with longer survival have been reported in most of the patients with gastroenteropancreatic (GEP) tumours. Patients who benefit the most from octreotide therapy are those with carcionid syndrome (successful control of diarrhoea, flushing episodes and wheezing) and VIPomas (control of diarrhoea). In patients with insulin-dependent diabetes mellitus (IDDM) octreotide suppresses GH levels, postprandial blood glucose increases with resultant decrease in daily insulin requirements. In women with polycystic ovary syndrome (PCOS) octreotide has inhibitory effect on serum LH and ovarian androgens. This could have beneficial effect on ovulatory performance in women with PCOS.
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PMID:[Clinical use of octreotide (Sandostatin) in endocrinology]. 799 11

Neuroendocrine gut and pancreatic tumors have over the years presented a therapeutic challenge. The patients present with a wide range of clinical symptoms related to hormone production that can sometimes be easily managed but are sometimes life threatening. The most frequent clinical symptom related to endocrine gut tumors is the carcinoid syndrome, with flushing, diarrhea, bronchoconstriction, and right heart failure. Until the middle of the 1980s, when a patient was not cured by surgery, very little could be offered except chemotherapy. Biotherapy has revolutionized the treatment of malignant neuroendocrine gut and pancreatic tumors, in which both interferon-alpha and somatostatin analogues improved the quality of life for these patients and possibly also increased survival. Chemotherapy, with response rates of 40% to 60% in endocrine pancreatic tumors, is still first-line treatment in this group of patients, whereas in patients with carcinoids of the gut, no beneficial value of chemotherapy so far has been noticed. Both interferon-alpha and somatostatin analogues provide biochemical responses in 40% to 70% of patients with carcinoid tumors, whereas significant tumor reduction is only noticed in a few cases. Development of biotherapy is just at its beginning, and in the future, when we have learned more about tumor biology and mechanisms of action of these treatments, even better therapeutic results might be encountered. Combinations of biotherapy with chemotherapy as well as combinations of different biotherapies are now under clinical investigation.
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PMID:Chemotherapy and biotherapy in neuroendocrine tumors. 809 14

Among endocrine tumors occurring in the gastrointestinal tract, midgut argentaffin EC cell carcinoids, gastric argyrophil ECL cell carcinoids, duodenal gastrin cell tumors, and rectal trabecular L cell carcinoids (in order of decreasing frequency) are those occurring more frequently. Together, they account for more than 80% of such tumors. Duodenal somatostatin cell tumors, gangliocytic paragangliomas, and differentiated neuroendocrine carcinomas are also well-defined tumor entities. The carcinoid syndrome, either classical, with intermittent flushing, hypotension, and diarrhea, or atypical, with persistent histamine-type red flushing, bronchospasm, and no diarrhea, and Zollinger-Ellison syndrome, with severe peptide ulcer disease, are the only hyperfunctional syndromes consistently found in association with these tumors. The carcinoid syndrome occurs in about 10% of gastrointestinal carcinoids, usually in their advanced, metastatic stage. The Zollinger-Ellison syndrome occurs in association with about 40% of intestinal gastrin cell tumors, including small intramural growths. Tumor prognosis depends on the mode and site of presentation, histology, cell type(s), size, level of invasion, metastases (especially distant metastases), and associated clinical syndrome or background disease. Hormones, trophic factors, inherited genetic traits, somatic mutations, and some chronic inflammatory processes are pathogenetically important in a large proportion of cases.
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PMID:The pathology of the gastrointestinal endocrine system. 812 73

Computed tomography during arterial portography (CTAP) and delayed high-dose iodine computed tomography (CT) have improved the preoperative localization of hepatic metastases from colon cancer. Nearly all patients presenting with malignant carcinoid syndrome have liver metastases, and removal of tumour bulk is considered the most effective means of management. To determine suitability for hepatic resection, CTAP and delayed high-dose iodine CT were used to evaluate the distribution of hepatic disease in two patients with malignant carcinoid syndrome. In both patients CTAP showed lesions not seen during recent dynamic incremented CT; the location of the lesions precluded resection. CTAP also demonstrated metastases less than 1 cm in diameter in one patient. Facial flushing (both patients) and hypotension (one) occurred during infusion of the contrast agent into the superior mesenteric artery. Because CTAP can demonstrate small hepatic metastases (less than 1 cm in diameter), it is recommended for patients with malignant carcinoid syndrome who are being considered for hepatic resection. The infusion of contrast media through the superior mesenteric artery may induce a carcinoid crisis, and prophylaxis with a somatostatin analogue is suggested.
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PMID:Computed tomography during arterial portography in malignant carcinoid syndrome: a report of two patients. 846 29

Carcinoids, tumors arising from enterochromaffin cells, represent the most common type of gastrointestinal endocrine neoplasm; they are often multiple and may appear anywhere in the gut. Carcinoid tumors may also occur in bronchi and ovaries. Classic symptomatology includes secretory diarrhea, flushing, edema, bronchospasm and cutaneous teleangectasias; however, over 30% of patients with demonstrably elevated serotonin levels may not exhibit any symptoms at all. The diagnosis of carcinoid tumor is typically made by measurement of 24-hour urinary excretion of 5-hydroxyindoloacetic acid. Commonly, tumor localisation is established with CT, US, NMR and arteriography. MIBG scintigraphy is also used to visualize tumors deriving from neuroendocrine cells as carcinoid. These tumors may express somatostatin receptors located on the cell surface. Therefore 111In Octreotide (Octreoscan), a somatostatin analogue, can be employed for tumor localisation. A 32-years-old man with liver metastases secondary to a carcinoid tumor of unknown origin is presented. Classic carcinoid symptoms were absent. Diagnosis was supported by elevated values of urinary 5-hydroxyindolocetic acid and liver fine-needle aspiration. Abdominal US and CT scan detected only liver masses but not the primary tumor. Arteriography was not performed. 131I MIBG and 111I octreotide scans both failed in locating the primary cancer too; only the second tracer showed marked uptake in liver metastases. Beside localization, these two tracers give also informations about the following therapy especially in malignant tumors where local resection isn't an adequate treatment.
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PMID:131I MIBG/111In octreotide mismatch in a patient with liver metastases secondary to a carcinoid of unknown origin. 853 97

1. SMS 201-995, a somatostatin analogue which interacts with highest affinities at somatostatin receptor subtypes 5 > 2 > or = 3, was microinjected into selective brain sites and its influence on pentagastrin (10 micrograms kg-1 h-1, i.v.)-stimulated gastric acid secretion was investigated in rats anaesthetized with urethane. Gastric acid secretion was measured by flushing the stomach with saline through a gastric cannula every 10 min. 2. SMS 201-995 microinjected into the dorsal vagal complex (DVC, 7, 15, 30 and 60 ng) dose-dependently increased pentagastrin-stimulated gastric acid secretion. The peak acid response was reached within 20 min and returned to basal level 50 min post-injection. SMA 201-995 (30 ng) microinjected into the surrounding area or the central amygdala did not modify pentagastrin-stimulated acid secretion. 3. SMS 201-995 injected into the lateral ventricle (i.c.v., 100, 200, or 300 ng), paraventricular nucleus (PVN) or lateral hypothalamus (LH) (7.5, 15, or 30 ng) dose-dependently inhibited pentagastrin-stimulated gastric acid secretion. SMS 201-995 (30 ng) microinjected into the area surrounding the PVN or LH did not modify the acid secretion response to pentagastrin. 4. Vagotomy prevented the effects of SMS 201-995 (30 ng) microinjected into the DVC and LH. 5. Spinal cord transection abolished the inhibitory action of SMS 201-995 (30 ng) microinjected into the PVN but not the LH. 6. These results demonstrate that SMS 201-995 acts in the DVC to enhance and in the LH and PVN to inhibit pentagastrin-stimulated gastric acid secretion. The action is mediated through vagal (DVC, LH)or spinal (PVN) pathways. The site specific pattern of acid responses to SMS 201-995 may be linked to the distribution of receptor subtypes at these sites that convey the different biological actions of somatostatin.
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PMID:SMS 201-995-induced stimulation of gastric acid secretion via the dorsal vagal complex and inhibition via the hypothalamus in anaesthetized rats. 856 64

Octreotide therapy is expensive, but at present it and other somatostatin analogues appear to offer the best opportunity of controlling the symptoms of flushing and diarrhoea. It may also have other properties affecting general well-being. The question of whether it changes tumour growth remains unanswered and there is no convincing evidence that it alters survival. In all published studies the numbers of patients are small and there have been no control groups. However, since no other drug has yet proved effective against flushing, the somatostatin analogues, including octreotide, remain the treatment of choice for the symptomatic control of the carcinoid syndrome. Octreotide is of great therapeutic value pre-operatively and intra-operatively and it is essential that all operating theatres have this drug available for immediate use. Surgical debulking, if feasible, provides the best outcome potential in carcinoid disease. Present evidence suggests that the place of octreotide and other somatostatin analogues is in controlling the symptoms of the disease rather than its progress and in ensuring cardiovascular and respiratory stability during surgical procedures.
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PMID:Octreotide therapy in carcinoid disease. 882 81

Carcinoid tumours derived from the neural crest are usually associated with the symptoms of flushing and diarrhoea in the presence of liver metastases. Scintigraphs with 131I-metaiodobenzylguanidine (131I-MIBG) which is accumulated in the argentaffin granules of the cell, as well as with 111In-pentetreotide for the imaging of somatostatin receptors on the cell surface, are positive in a large proportion of carcinoid patients. To evaluate the complementary role of both radionuclide tests, we studied 20 consecutive carcinoid patients: 14 with the characteristic carcinoid syndrome and 6 with tumour symptoms, such as pain or obstruction. A positive test was found in 84% with either 131I-MIBG or 111In-pentetreotide; the combination yielded a sensitivity of 95%. A positive correlation was found with the presence of the carcinoid syndrome, but not with 5-HIAA excretion. A positive test may help in adjusting treatment: either to predict the response to octreotide or to select patients for 131I-labelled MIBG treatment. Application of a therapeutic dose of 111In-pentetreotide may be limited by the high normal uptake in the kidneys.
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PMID:Combined diagnostic imaging with 131I-metaiodobenzylguanidine and 111In-pentetreotide in carcinoid tumours. 894 76


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