Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P61278 (somatostatin)
 22,083 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Octreotide, a long-acting somatostatin analogue has recently been introduced in the therapy of gastroenteropancreatic endocrine tumors, but home experience has been lacking. With the aim of drawing attention to this therapeutic possibility, a case of malignant carcinoid syndrome treated with octreotide for 18 months is reported. Despite the therapeutic attempts preceding the octreotide administration a gradual progression in clinical symptoms was observed and cardiac failure due to fibrotic and valvular heart disease developed. Cytotoxic chemotherapy, serotonin antagonists or repeated selective embolisation of the hepatic artery only resulted in a short transitional improvement. Octreotide in a dose of 100 micrograms three times daily by subcutaneous injection provided effective and rapid relief from episodic flushing and serious diarrhoea. Plasma level of serotonin and 24-hour urinary excretion of 5-hydroxyindolacetic acid decreased from 6 micrograms/ml to 2 micrograms/ml and from 800 mumol/day to 70 mumol/day, respectively. No changes in the number and extension of liver metastases could be seen after introducing the octreotide treatment. The patient's compensated cardiac status could be preserved and continuous therapy provided an acceptable quality of life.
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PMID:[Treatment of carcinoid syndrome with a somatostatin analogue]. 137 69

In unusual cases of flushing and anaphylaxis, and after the elimination of the more obvious causes of anaphylaxis or those that may be evaluated by readily available techniques, it is possible to confront a limited and difficult differential diagnosis, which includes idiopathic flushing, anaphylaxis, and neoplastic syndromes associated with mastocytosis and carcinoid tumor. Interestingly, there are rather few features that distinguish one of these possibilities from another. However, the presence of allergic signs and symptoms tend to favor the diagnosis of recurrent idiopathic anaphylaxis; and right-sided valvular heart disease, the presence of excessive 5-HIAA in the urine, and a response to somatostatin favor the diagnosis of carcinoid syndrome. The distinguishing features of mastocytosis include the presence of characteristic skin lesions and diagnostic histopathologic findings on bone marrow biopsy. Counts of absolute mast cell numbers in the skin are less helpful. Following such guidelines, it is often possible to focus on the most likely diagnosis, be it idiopathic anaphylaxis, benign cutaneous flushing, mastocytosis, or carcinoid tumor.
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PMID:Differential diagnosis of the patient with unexplained flushing/anaphylaxis. 1074 48

Carcinoid syndrome originates from metastatic carcinoid tumors localized in the gastrointestinal system, pancreas, biliary vessels, bronchi, ovaries, and testes; it is characterized by flushing, telangiectasias, diarrhea, bronchoconstriction, and fibrous endocardial plaques in the heart. Cardiac involvement is detected by echocardiography in over 50% of patients with this syndrome. Right-sided valvular heart disease occurs frequently in patients with carcinoid syndrome, involving most commonly the tricuspid and pulmonary valves. Involvement of the left-sided valves rarely occurs. Medical therapy for carcinoid heart disease includes digitalis and diuretics for congestive heart failure symptoms; the effects of carcinoid syndrome can be treated with the use of somatostatin analogues. Conventional chemotherapy has been of little beneficial value, with response rates of only 10% to 30%. The use of octreotide, a long-acting and potent somatostatin analogue, is a major advance in the management of carcinoid tumors. In addition to providing effective symptom relief in malignant carcinoid syndrome, octreotide can also be used for diagnostic purposes. Despite its expense, octreotide is the current agent of choice for the treatment of this condition. Analogues with different receptor specificities and pharmacokinetics hold promise for the future. Valve surgery is the only definitive treatment for intractable right-sided heart failure. Although cardiac surgery carries high perioperative mortality, marked symptomatic improvement occurs in survivors. Surgical intervention therefore should be considered in the appropriate patients when cardiac symptoms become severe. Balloon valvulotomy in patients with severe pulmonary artery stenosis often results in palliation of symptoms; however, surgery still is required often in these patients.
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PMID:Carcinoid Heart Disease. 1109 44

Midgut carcinoids developing in the small intestine represent the most common cause of the carcinoid syndrome, with severe symptoms of flush, diarrhoea, and fibrotic valvular heart disease. The tumours may be histologically identified with specific chromogranin A or synaptophysine immunostainings, and by serotonin reactivity, which supports a midgut origin. Urinary 5-HIAA excretion and serum chromogranin A measurements are used as biochemical tumour markers for clinical diagnosis, and as important monitors of treatment effects and prognostic predictors. The midgut carcinoids have typically slow proliferation and extended disease course, and surgical treatment has become increasingly important for their management. Surgery should aim to remove primary tumours and mesenteric metastases, which may cause long-term abdominal complications, by typical fibrotic intestinal entrapment and small bowel ischaemia due to encasement of mesenteric vessels. Attempts should also be made to surgically remove or ablate liver metastases, since this may significantly contribute to palliation of the carcinoid syndrome. In patients with this syndrome surgery is combined with continuous biotherapy with long-acting somatostatin analogues and interferon, which may alleviate symptoms and cause stable disease with slow progression. Favourable survival and life-quality can be expected with this treatment also in patients with advanced midgut carcinoids.
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PMID:Management of midgut carcinoids. 1571 73

In acromegaly, growth hormone (GH) and insulin-like growth factor-1 (IGF-1) excess results in a specific cardiomyopathy characterized by concentric cardiac hypertrophy primarily associated with diastolic dysfunction that can lead to impaired systolic function and eventually heart failure. This review of the literature evaluates the effect of therapeutic intervention on cardiac parameters. Clinical studies investigating the impact of treatments for acromegaly on cardiac function published between January 1980 and January 2009 were identified through electronic searches of Medline. Suppression of GH and IGF-1 following surgery or medical treatment with somatostatin analogue therapy is effective in decreasing left ventricular (LV) hypertrophy, with subsequent improvement in cardiac function. First-line treatment with somatostatin analogues resulted in improved cardiac outcome compared with first-line surgery, possibly due to somatostatin analogues acting directly through somatostatin receptors on cardiac cells. Additional cardiac improvement has been reported when somatostatin analogue treatment was combined with surgery. In patients where complete biochemical control was not achieved, an improved cardiac performance following treatment with somatostatin analogues has been reported. Treatment with pegvisomant has been demonstrated to reduce LV hypertrophy and improve diastolic and systolic performance. In contrast, reports have suggested that treatment with the dopamine agonist cabergoline increased the incidence of valvular heart disease. Although surgery and somatostatin analogues are effective in improving cardiomyopathy, a greater beneficial effect is observed with somatostatin analogue treatment. Selected patients with acromegaly should consider first-line therapy or pre-treatment with somatostatin analogues prior to surgery to achieve biochemical control and improve cardiac dysfunction.
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PMID:Improvement of cardiac parameters in patients with acromegaly treated with medical therapies. 2171 28

The prevalence of intestinal neuroendocrine tumours, also known as carcinoid tumours, has increased significantly over the past three decades. Tumours of the distal small intestine (midgut) are often indolent, but are characterized by a high potential to metastasize to the small-bowel mesentery and liver. Patients with distant metastases are prone to development of the carcinoid syndrome, a constellation of symptoms which includes flushing, diarrhoea, and valvular heart disease. The carcinoid syndrome is caused by secretion of serotonin and other vasoactive substances into the systemic circulation. Treatment options for metastatic intestinal NETs have expanded in recent years. Of particular importance has been the development of somatostatin-analogue therapies. Somatostatin analogues were originally introduced for palliation of the carcinoid syndrome; however recent clinical trials have demonstrated that they can exert an inhibitory effect on tumour growth. Other novel agents targeting the VEGF and mTOR pathways have recently been evaluated in phase III trials, however their role in the management of small-intestinal NETs remains controversial. This article examines the biological characteristics of small intestinal NETs, summarizes current guidelines on classification, staging and grading, and reviews developments in locoregional and systemic therapy.
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PMID:Neuroendocrine tumours of the small intestine. 2358 17

Gastroenteropancreatic neuroendocrine tumors (GEP-NETs) are rare, generally indolent neoplasms that can arise throughout the gastrointestinal system. Some GEP-NETs, known as functional, secrete hormones that can lead to a complex of symptoms. Classical carcinoid syndrome is associated with flushing, diarrhea, bronchospasm, and symptoms of valvular heart disease. GEP-NETs are classified according to the primary tumor site, functionality of the disease, and histology. Treatment is guided by the resectability of the tumor, the location and extent of metastases, and the presence of clinical symptoms. Typically, first-line treatment of patients with unresectable disease includes the use of somatostatin analogs, such as octreotide LAR depot or lanreotide depot/autogel, which was recently approved by the US Food and Drug Administration for treatment of GEP-NETs. Somatostatin analogs can improve the severe diarrhea/flushing episodes that may be associated with metastatic carcinoid tumors. For patients with pancreatic NETs, additional approved treatment options include the targeted agents everolimus and sunitinib, which have demonstrated antitumor activity. Chemotherapy may also have a selective role, particularly in pancreatic NETs. Localized approaches, including cytoreductive surgery, hepatic arterial embolization, and ablative therapies, may be used for palliative treatment in patients with liver metastases.
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PMID:New and Emerging Treatment Options for Gastroenteropancreatic Neuroendocrine Tumors. 2643 Sep 56

Gastroenteropancreatic neuroendocrine tumors (GEP-NETs) are rare malignancies that originate in the gastrointestinal system. GEP-NETs are typically indolent, but tumors known as "functional" secrete hormones that can lead to a complex of symptoms, including flushing, diarrhea, bronchospasm, and valvular heart disease. Management of patients with GEP-NETs requires a multidisciplinary approach, as treatment modalities include surgery, radiology, and pharmacotherapy. The available pharmacologic agents have increased in recently, and now include cytotoxic chemotherapies, somatostatin analogues, multitargeted tyrosine kinase inhibitors, mammalian target of rapamycin inhibitors, and radioisotopic radiotherapies. The optimal sequencing of treatments is unknown. Advances in the management of GEP-NETs have been based on the results of recently completed clinical trials that have shown improvement in disease outcome and symptom management. The amount of positive data that has emerged from these studies is unprecedented in the GEP-NETs field. At the 2017 American Society of Clinical Oncology Gastrointestinal Cancers Symposium, several abstracts provided subanalyses of previous trials and new data for emerging treatments. Management will likely evolve as these therapies are incorporated into clinical care.
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PMID:Recent advances in the management of gastroenteropancreatic neuroendocrine tumors: insights from the 2017 ASCO Gastrointestinal Cancers Symposium. 2865 22

Small bowel neuroendocrine tumors (SBNETS) are slow-growing neoplasms with a noted propensity toward metastasis and comparatively favorable prognosis. The presentation of SBNETs is varied, although abdominal pain and obstructive symptoms are the most common presenting symptoms. In patients with metastases, hypersecretion of serotonin and other bioactive amines results in diarrhea, flushing, valvular heart disease, and bronchospasm, termed carcinoid syndrome. The treatment of SBNETs is multimodal and includes surgery, liver-directed therapy, somatostatin analogues, targeted therapy, and peptide receptor radionuclide therapy.
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PMID:Management of Small Bowel Neuroendocrine Tumors. 3215 57

Carcinoid syndrome (CS) is a paraneoplastic syndrome caused by the release of serotonin and other substances from well-differentiated neuroendocrine tumors (NETs). The hallmark symptoms of carcinoid syndrome are flushing and diarrhea; atypical signs and symptoms can include wheezing, abdominal pain, valvular heart disease, telangiectasias, pellagra, and the complications of mesenteric fibrosis, including ureteral obstruction, bowel obstruction, and bowel ischemia. These symptoms are mediated by the release of serotonin (5-HT), histamine, kallikrein, prostaglandins, and tachykinins. The diagnosis of CS requires these symptoms and corresponding elevations in lab tests. Treatment options include surgery and medical management with somatostatin analogs.
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PMID:Carcinoid Syndrome: A Review. 3225 25


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