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)

The carcinoid syndrome, a common feature of small intestinal carcinoid tumors with liver metastases, includes flushing, diarrhea, bronchoconstriction, and right heart failure. The etiology of the carcinoid syndrome is not well understood, but serotonin seems to be involved in the diarrhea, whereas tachykinins may play a role in the flush reaction. In a double blind placebo-controlled study, we studied the effect of octreotide in 20 patients with midgut carcinoid tumors and liver metastases. A sc injection of 50 micrograms octreotide caused a significant (P less than 0.001) decrease in median plasma tachykinins and serum pancreatic polypeptide, GH, and insulin for up to 4 h. Administration of octreotide (50 micrograms, twice daily, sc) caused a 26% decrease in urinary 5-hydroxyindoleacetia acid excretion, but the number of flushing attacks or bowel movements did not change significantly. A typical flush was provoked by pentagastrin, and plasma tachykinin and serotonin levels were measured. The flush reaction was graded on a 10-point visual analog scale. Octreotide (50 micrograms, sc) given 45 min before flush stimulation prevented tachykinin release completely and significantly reduced the median flushing score from 8.5 to 2. Placebo administered in the same way did not prevent tachykinin release after pentagastrin administration. Thus, octreotide prevents pentagastrin-induced flushing and the related hormonal changes in patients with the carcinoid syndrome.
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PMID:The effects of octreotide on basal and stimulated hormone levels in patients with carcinoid syndrome. 246 45

Octreotide is a long-acting cyclic octapeptide with pharmacologic actions mimicking those of the natural hormone somatostatin. It can suppress the secretion of serotonin, as well as the gastroenteropancreatic peptides gastrin, vasoactive intestinal peptide (VIP), insulin, glucagon, secretin, motilin, and pancreatic polypeptide. It also suppresses growth hormone and decreases splanchnic blood flow. Octreotide is completely and rapidly absorbed following subcutaneous injection and has an elimination half-life of 1.5 hours. Clinical trials reviewed here show octreotide useful in the treatment of diarrhea associated with VIP secreting tumors, as well as diarrhea and flushing associated with carcinoid syndrome, both conditions for which the drug is approved. Clinical trials involving the use of octreotide in the treatment of acromegaly are also reviewed. Adverse reactions to octreotide are mild to moderate and most commonly involve injection site pain and diarrhea. Drug interactions are apparently related to the drug's pharmacologic effects. Octreotide is given subcutaneously two to three times daily, with daily doses ranging from 50mcg to 1,500mcg per day. Further research appears necessary to clarify dosing issues.
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PMID:Debut of a somatostatin analog: octreotide in review. 255 39

We describe a 63-yr-old man with disseminated medullary carcinoma of the thyroid and pancreatic nesidioblastosis and microadenosis with pancreatic polypeptide (PP) hypersecretion. His major symptoms were watery diarrhea, flushing, and abdominal bloating; these and the elevated plasma PP levels did not change after resection of the distal two thirds of the pancreas, which contained a 2-cm mass of nesidioblastotic tissue. Postoperatively, a long-acting somatostatin analog, SMS 201-995 (100 micrograms/day), normalized PP secretion acutely and chronically (7 months) and ameliorated his symptoms. The analog had no side-effects and did not alter glucose tolerance, calcitonin hypersecretion, or growth of the medullary carcinoma, but it did inhibit GH secretion. After withdrawal from therapy for 1 month, PP hypersecretion and all symptoms except diarrhea recurred. The coexistence of medullary carcinoma of the thyroid and PP cell nesidioblastosis represents a new variant of the overlap syndromes between multiple endocrine neoplasia types I and II. Patients with medullary carcinoma and unexplained watery diarrhea should have fasting gastroenteropancreatic hormone assays done to screen for a potential gastrointestinal or pancreatic origin for the diarrhea.
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PMID:Medullary carcinoma of the thyroid, pancreatic nesidioblastosis and microadenosis, and pancreatic polypeptide hypersecretion: a new association and clinical and hormonal responses to long-acting somatostatin analog SMS 201-995. 288 96

Calcitonin gene-related peptide (CGRP) is a recently discovered widespread regulatory peptide which is encoded in the same gene as calcitonin. We assessed the effect of systemic infusion of synthetic rat CGRP at low dose (range 0.32-2.56 pmol/kg per min) on submaximal pentagastrin-stimulated gastric secretion and on gastrointestinal hormones. To assess its pharmacokinetic parameters in man the MCR and plasma half-life were estimated by the continuous infusion method. Gastric acid output and pepsin secretion were significantly reduced by CGRP (-29% of basal, P less than 0.01 and -40% of basal, P less than 0.005, respectively). There was a significant fall in basal levels of gastrin (-39%, P less than 0.001); gastric inhibitory peptide (-44.7%, P less than 0.001); enteroglucagon (-25%, P less than 0.001) and neurotensin (-33%, P less than 0.05). There was no significant change in plasma levels of insulin, motilin, pancreatic polypeptide or glucose. Suppression of gastric secretion and the fall in gastrointestinal hormones was prolonged and basal levels were not re-established after stopping the CGRP infusion. The disappearance curve of immunoreactive CGRP from the plasma was bi-exponential. The plasma half-life of immunoreactive CGRP was calculated as 6.9 +/- 0.9 min for the fast decay and 26.4 +/- 4.7 min for the slow decay. The calculated MCR was 11.3 +/- 1.2 ml/kg per min. Except for flushing of the face no untoward effects were observed. The results of this study suggest the possibility that CGRP could play a role in the regulation of gastric secretion and gastrointestinal hormone release.
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PMID:Infusion of a novel peptide, calcitonin gene-related peptide (CGRP) in man. Pharmacokinetics and effects on gastric acid secretion and on gastrointestinal hormones. 392 13

The intestinal carcinoid tumors of 26 patients were stained for the presence of serotonin, gastrin, somatostatin, motilin, secretin, glucagon, pancreatic polypeptide, ACTH, and neurotensin. Argentaffin and argyrophil stains were also performed in all cases. Thirty-five separate tumors (counting metastases and multiple primaries) from the 26 patients were studied. Serotonin was present in 30 of the 35 tumors. Nineteen tumors contained serotonin only. Fourteen tumors contained multiple neuroendocrine products. One tumor contained gastrin only. One tumor did not stain immunohistochemically, but was argyrophilic. Metastatic deposits were studied in nine patients. Some metastases produced the identical neuroendocrine products as the primary tumor, whereas others produced either additional or fewer hormones than the primary tumor. Moreover, different metastases from the same primary tumor were observed to produce different hormones. Argyrophilic cells were present in all cases and were much more numerous than cells staining by immunohistochemistry. Argyrophilic cells probably contain monoamines and polypeptide hormones in addition to those studied in this series. The argyrophil stain was the best general stain in this study for the demonstration of neuroendocrine cells. Argentaffin staining was negative in ten cases that were serotonin positive and two argentaffin positive cases were serotonin negative. The carcinoid syndrome, as clinically defined by the presence of flushing and diarrhea, was noted in five patients, all of whom had serotonin-containing small bowel carcinoids. Endocrine-related symptoms were not clinically appreciated in the remaining patients.
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PMID:The neuroendocrine products of intestinal carcinoids. An immunoperoxidase study of 35 carcinoid tumors stained for serotonin and eight polypeptide hormones. 618 28

We report here 2 patients with somatostatin-secreting tumours and hypersomatostatinaemia. One subject, a 36 year old woman with diabetes, flushing, labile blood pressure and diarrhea, had elevated basal plasma levels of somatostatin-like immunoreactivity (SLIR) and calcitonin. Plasma SLIR increased further following tolbutamide administration. Plasma levels of prostaglandin E2 (PGE2) and pancreatic polypeptide (PP), normal in the basal state, showed exaggerated responses to pentagastrin and secretin, respectively. Immunocytochemistry of the tumour tissue revealed cells containing somatostatin-, calcitonin-, PGE2- and PP-like immunoreactivity. The other patient, a 52 year old male, had an SLIR-secreting tumour of the proximal duodenum and elevated basal and post-tolbutamide SLIR levels but no signs or symptoms suggestive of increased SLIR production. Tumour tissue revealed cells containing somatostatin- and calcitonin-like immunoreactivity. We conclude that patients with somatostatinomas do not always exhibit a predictable syndrome. Patients with these tumours may exhibit a range of clinical, biochemical and immunocytochemical features typical of endocrine tumours of mixed-cell origin, such that the dominant signs and symptoms associated with these neoplasms cannot readily be ascribed to overproduction of any single hormone.
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PMID:Somatostatinoma syndrome: does a clinical entity exist? 629 17

A gastric tumor was found in a 64-year-old woman who later developed flushing, tachycardia, headache, and lacrymation. The plasma pancreatic polypeptide (PP) level was 700 times normal values, and the majority of the tumor cells were immunoreactive to PP antiserum. Symptoms were alleviated, and PP levels fell after embolization of the hepatic artery for liver metastases. This is the first reported case of gastric PP-producing endocrine tumor.
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PMID:A pancreatic-polypeptide-producing tumor of the stomach. 646 36

Gastroenteropancreatic (GEP) neoplasms originate from any of the various cell types belonging to the neuroendocrine system. A general characteristic of GEP endocrine tumours is that the vast majority produce and secrete a multitude of peptide hormones and amines. Many patients with malignant metastasising tumours present clinical symptoms related to hormone hyperproduction. These include the so-called carcinoid syndrome, characterised by flushing, diarrhoea, wheezing and right heart disease, which is predominantly associated with the serotonin- and tachykinins-producing carcinoids of the midgut. Several types of syndrome associated with GEP endocrine tumors are caused by overproduction of a specific hormone. For instance, the well-known Zollinger-Ellison syndrome is gastrin-mediated. The so-called 'insulinoma syndrome' depends on excessive production of insulin and proinsulin, resulting in hypoglycemia. The 'glucagonoma syndrome' is characterised by necrolytic migratory erythema, diabetes and diarrhoea. The Verner-Morrison syndrome, which is brought about by high circulating levels of vasointestinal peptide (VIP). produces severe secretory diarrhoea. Finally the 'somatostatinoma syndrome' involves gallbladder dysfunction and gallstones, diarrhoea with or without steatorrhea, and impaired glucose tolerance. The biochemical diagnosis of endocrine digestive tumors is based on general and specific markers. The best general markers are chromogranin A (CgA) and pancreatic polypeptide (PP). Specific markers for endocrine tumors include insulin, gastrin, glucagon, vaso intestinal polypeptide (VIP), somatostatin and the primary cathabolic product of serotonin, 5-hydroxyndoleacetic acid (5-HIAA). Localisation procedures commonly applied, in the diagnosis of endocrine tumours include ultrasound (US), computed tomography (CT) and somatostatin receptor scintigraphy (SRS).
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PMID:Epidemiology, clinical features and diagnosis of gastroenteropancreatic endocrine tumours. 1176 60