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)

A review is given on the clinical features of carcinoid syndrome including symptomatology, diagnostics, biochemistry and treatment. We have reviewed the literature on current therapy of carcinoid patients with special emphasis on the use of the somatostatin analogue SMS 20-1995. In addition, we present data on the effects of SMS 201-995 on indices of a clinical, biochemical and tumor growth. Diarrhea is abolished or significantly reduced in 75% of patients, flushing improves in 100%, wheezing in 100% with a decrease in airways resistance, and in one patient myopathy has improved. Blood serotonin is notoriously resistant to intervention and urinary 5-HIAA will decrease in 75% of causes but subsequently rebounds in 38%. Tumors, in general, continue to grow, but this may be slowed or in rare cases tumor growth is arrested. In individual instances the tumor may even infarct, leading to spontaneous cure. Tumors secreting PP, ACTH and calcitonin may be particularly resistant to treatment, whereas VIP secreting tumors appear to be sensitive.
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PMID:Clinical features of carcinoid syndrome and the use of somatostatin analogue in its management. 266 49

Symptomatology and pathophysiology of carcinoid syndrome are summarized and the therapeutic possibilities reviewed. It is underlined that severity of symptoms and effect of the disease on vital organ function should be considered in order to tailor treatment appropriately. In some patients with a mild syndrome, symptomatic treatment of diarrhea may be sufficient while more aggressive treatment with cytotoxic drugs, interferon, somatostatin analogue or hepatic artery occlusion may be indicated in patients with severe symptoms. Carcinoid crisis is a serious, life-threatening complication of carcinoid syndrome and in this condition somatostatin analogue seems to be an especially useful addition to the therapeutic arsenal.
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PMID:Therapeutic considerations for the malignant carcinoid syndrome. 266 50

Octreotide is an analogue of somatostatin. Like endogenous somatostatin, it exerts a potent inhibitory effect on the release of anterior pituitary growth hormone and thyroid-stimulating hormone, and peptides of the gastroenteropancreatic endocrine system, while overcoming some of the shortcomings of exogenously administered somatostatin, namely a short duration of action, a need for intravenous administration and postinfusion rebound hypersecretion of hormone. Clinical studies have shown that octreotide is effective in the treatment of acromegaly and thyrotrophinomas. In comparative trials octreotide was significantly superior to bromocriptine in patients with acromegaly. Octreotide also appears to provide a significant advantage over existing therapies in the management of the carcinoid syndrome and offers considerable therapeutic potential in reversing carcinoid crises which may be life-threatening. Trials in patients with tumours producing vasoactive intestinal peptide demonstrated that octreotide may be an effective first-line choice for this condition, which has usually metastasised and become refractory to traditional symptomatic therapy. In limited studies in patients with high-output secretory diarrhoea, including cryptosporidium-related diarrhoea associated with AIDS and in patients with small bowel fistulas, octreotide has been shown to be effective in reducing stool/fistula output. However, well-designed clinical trials are still required to confirm its long term usefulness in these disorders. Similarly, although the use of octreotide in other conditions such as neonatal hypoglycaemia caused by nesidioblastosis, reactive pancreatitis, insulin-dependent diabetes mellitus, postprandial hypotension and the dumping syndrome has provided encouraging preliminary results, more studies are needed to clarify the place of octreotide in their treatment. Overall, octreotide appears to be well tolerated with the most frequently reported reactions being pain at the site of injection and gastrointestinal symptoms such as abdominal cramps, nausea, bloating, flatulence, diarrhoea and steatorrhoea. These adverse effects usually abate with time. Additionally, octreotide, like endogenous somatostatin, may also result in cholelithiasis, presumably by altering fat absorption and possibly by decreasing motility of the gallbladder. Thus, octreotide represents a new departure from traditional therapies in the treatment of various pathophysiological states associated with excessive peptide production and secretion. It offers a significant advantage over existing therapies in the medical management of patients with acromegaly, thyrotrophinomas, the carcinoid syndrome, tumours producing vasoactive intestinal peptide and severe secretory diarrhoea in whom conventional management options have either become exhausted or have provided suboptimal symptomatic relief.
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PMID:Octreotide. A review of its pharmacodynamic and pharmacokinetic properties, and therapeutic potential in conditions associated with excessive peptide secretion. 268 36

Somatostatin analog, SMS 201-995, effectively inhibits the release of hormones from gastrointestinal endocrine tumors and reduces hormonally mediated diarrheas. Its clinical efficacy in nonhormonally mediated diarrhea is limited, despite a potent antisecretory and proabsorptive effect in vitro. The effect of serosal addition of SMS 201-995 on in vitro short-circuit current responses in rat intestine is dependent upon chloride and more marked in colon and ileum than jejunum. In contrast, in vivo loop studies demonstrated that systemic administration of SMS 201-995 for five consecutive days produced a paradoxical decrease in basal colonic fluid absorption with no effect in jejunum or ileum. Furthermore, systemically administered SMS 201-995 did not alter cholera toxin-stimulated intestinal secretion. We conclude that despite a previously identified intestinal antisecretory and proabsorptive effect of SMS 201-995 in vitro, this effect is not seen in vivo and may explain the limited use of SMS 201-995 as an antidiarrhoeal agent in nonhormonally mediated diarrhoea.
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PMID:Effect of somatostatin analog (SMS 201-995) on in vivo intestinal fluid transport in rats. A limited systemic effect. 270 88

A 29-year-old male presented with acromegaly and hyperthyroidism and was found to be hypersecreting both GH and TSH. A somatostatin analogue, SMS 201-995, at doses of 50 and 100 micrograms s.c. 3 times a day produced an acute decrease in serum GH and TSH levels to less than 20% of basal concentrations. An increase in serum SMS 201-995 levels preceded the decline in serum GH and TSH levels. Partial resolution of signs and symptoms related to GH excess occurred and the patient developed normal serum thyroxine levels. These latter effects were maintained during the 3.5 months of SMS 201-995 therapy; however, pituitary adenoma size as judged by MRI was unchanged. Side effects of therapy were minimal and included transient abdominal pain, diarrhea and weight gain. Adenomatous pituitary tissue was surgically removed and placed in monolayer culture. It was observed that SMS 201-995 produced significant inhibition of GH and TSH release. Histology revealed a partly chromophobic, partly acidophilic adenoma containing GH and TSH. Electron microscopy showed a pituitary adenoma which appeared to consist of smaller cells resembling somatotrophs and larger cells exhibiting ultrastructural features of thyrotrophs. Immunoelectron microscopy localized the two biochemically distinct peptides in the same cell type, often in the same secretory granules. No morphologic abnormality, attributable to SMS 201-995 medication, was evident. Thus it can be concluded that pituitary adenomas can simultaneously secrete GH and TSH which produce acromegaly and hyperthyroidism. These bi-hormonal tumors may synthesize GH and TSH in the same cell type.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Response of a GH- and TSH-secreting pituitary adenoma to a somatostatin analogue (SMS 201-995): evidence that GH and TSH coexist in the same cell and secretory granules. 271 53

We have observed two patients with AIDS suffering from severe watery diarrhea refractory to conventional medical treatment. In the first patient the reason for the diarrhea could not be revealed in spite of extensive investigations; however, the clinical picture suggested cryptosporidia infection. In the second patient cytomegalovirus could be shown in colonic biopsy specimens. After failure of several attempts of symptomatic, antibiotic, and antiviral therapy, the long-acting somatostatin analogue SMS 201-995 was administered to the patients subcutaneously in a dose between 2 x 50 micrograms and 3 x 100 micrograms/day. This treatment resulted in a prompt reduction of stool volume and bowel motions. Somatostatin may be a useful addition to the symptomatic treatment of refractory diarrhea in AIDS.
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PMID:Treatment of secretory diarrhea in AIDS with the somatostatin analogue SMS 201-995. 272 69

A 27 month old girl with congenital microvillus atrophy received two courses of SMS 201-995, a synthetic long acting analogue of native somatostatin, in an attempt to decrease profuse secretory diarrhoea. During the first trial at 13 months of age fluid and electrolytes administered by parenteral infusion were decreased as measured by water and faecal electrolyte losses. During the second trial of SMS 201-995 at 19 months fluid and electrolyte input were held constant for 14 days. Stool volume declined from 275 ml/kg to 161 ml/kg. Reductions in output of stool electrolytes (Na+, K+, Cl-) were accompanied by an increase in urine fluid output and increased excretion of urinary Na+. Subsequent administration of SMS 201-995 for a nine month period was not associated with adverse side effects or an impairment of growth velocity. These findings suggest that SMS 201-995 may be useful therapy in infants with high output diarrhoea as a result of congenital microvillus atrophy.
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PMID:Clinical response to the long acting somatostatin analogue SMS 201-995 in a child with congenital microvillus atrophy. 275 84

A 69 year-old male with carcinoid syndrome and undetectable primary tumour, but disseminated liver metastases, was treated with somatostatin analogue octreotide (Sandostatin) and later additionally with recombinant interferon alpha 2 b (r IFN alpha 2 b, Intron A). The carcinoid symptoms (flushing, diarrhoea) were stopped within hours by octreotide. Simultaneously, the urinary 5-hydroxyindolacetic acid (5-HIAA) excretion and serum serotonin levels decreased by more than 50%. In spite of continued treatment with r IFN alpha 2 b a reduction in dosage of octreotide resulted in a rapid recurrence of carcinoid symptoms, suggesting that IFN alpha 2 b had no effect on the carcinoid symptoms in this patient. Since, furthermore, no regression of the tumour mass was observed, treatment with IFN was stopped after 8 months. During 15 months of treatment to date the patient has been kept free of symptoms by octreotide.
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PMID:[Therapy of metastatic carcinoid with the somatostatin analog octreotide and with recombinant interferon alfa 2b]. 276 66

We have reviewed data pertinent to three tumor syndromes that derive from overproduction of three GEP peptide hormones. The clinical syndrome of somatostatin excess remains well defined with diabetes, diarrhea, steatorrhea being predominant features. With the availability of assays and increasing awareness, more cases are being diagnosed in the intestine and these differ somewhat in their presentation with cholecystitis, GI bleeding, or a mass as the cardinal features. An unusual association with MEN II pheochromacytoma and neurofibromatosis is emerging. PPomas remain enigmatic. Although diarrhea is a feature, these tumors are usually silent and present with hypatomegally, abdominal pain, and jaundice because of the large size and malignant nature. Neurotensinomas remain rare and truly difficult to separate from the symptom complex produced by VIP excess. Edema, hypotension, cyanosis and flushing should alert one to the possibility of a neurotensin-secreting tumor.
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PMID:Somatostatinomas, PPomas, neurotensinomas. 282 62

The long-acting somatostatin analogue SMS 201-995 was administered to a six-month-old infant with intractable diarrhea after failure of conventional treatment. During eight weeks of treatment, the secretory component of the diarrhea was positively influenced with a reduction of daily stool weight and stool sodium concentration. Plasma levels of growth hormone were markedly, and levels of insulin, IGF I, gastrin, pancreatic polypeptide, VIP, and neurotensin moderately decreased. Linear growth was also inhibited. The patient unexpectedly died from fulminant colitis at a time, when the dosage had been reduced from 18 to 3.5 micrograms/kg/day. The relationship, if any, between therapy with SMS 201-995 and the colitis remained unclear. It is concluded that SMS 201-995 can be effective in reducing secretory diarrhea in infants. However, further studies are necessary to assess the safety of its administration in this age group.
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PMID:Effects of the long-acting somatostatin analogue SMS 201-995 in an infant with intractable diarrhea. 284 5


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