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)

Diabetes mellitus, steatorrhea, cholelithiasis and a tumor distorting the duodenum prompted a work-up for somatostatinoma in a 52-year-old man. The responses of pancreatic B-cells but not of A-cells to nutrient stimuli were inhibited, and growth-hormone release was suppressed, suggesting somatostatin resistance in some target tissues. Plasma somatostatin-like immunoreactivity ranged from 9000 to 13,000 pg per milliliter (normal: 88+/-8, mean +/- S.E.M.) and was distributed in four molecular forms, including free somatostatin. The primary tumor contained 5 microgram of somatostatin-like immunoreactivity per milligram of wet tissue, distributed in three of the molecular forms noted in plasma. Plasma calcitonin was also elevated (4650 pg per milliliter; normal: less than 120). Immunocytochemical studies showed that cells of the primary tumor contained somatostatin and calcitonin but no other peptide hormones. Only somatostatin was present in the metastases. Somatostatin was localized electron microscopically in all secretory granules, irrespective of size and shape, whereas calcitonin was present only within a single subpopulation of small granules in the same cells.
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PMID:Somatostatinoma syndrome. Biochemical, morphologic and clinical features. 37 80

The frequency of gallstones during long-term treatment with the somatostatin analogue octreotide reported in different studies varies from 0% to 50%, the reason for this variation being unknown. Therefore, we examined 58 acromegalic patients undergoing different treatment regimens for the frequency of gallstones. Thirteen were treated with octreotide, 20 with bromocriptine, and 25 had no medical treatment after successful neurosurgery. Also, 58 patients without known gallbladder disease served as controls. The postprandial gallbladder contraction was also investigated in 27 acromegalic patients (10 with octreotide, 10 with bromocriptine, and 7 with no medical therapy). Ten of the 58 acromegalic patients were found to have gallstones, 4 of 25 receiving no medical treatment, 4 of 20 treated with dopamine agonists, and 2 of 13 treated with octreotide. In 9 of the 58 control patients, gallstones were detected. Although in the octreotide group the gallstones were newly formed under therapy, there was no difference in gallstone prevalence between the different treatment regimens and the control group. However, the postprandial gallbladder contraction was significantly more often inhibited during octreotide therapy, and this effect was most pronounced during the first hours following injection. Differences in the timing of injections therefore may be an explanation of the variable incidence of cholelithiasis in the different studies.
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PMID:Gallstones in acromegalic patients undergoing different treatment regimens. 135 30

The recent availability of the long-acting somatostatin analogue, octreotide, has allowed its therapeutical use in a wide variety of human diseases, including some digestive, neoplastic and autoimmune disorders. This review focuses on the treatment of some endocrine disorders with octreotide. Evidence is accumulating that octreotide treatment is effective in improving the cure rate of pituitary surgery in acromegaly by shrinking the tumour size, and in lowering GH and IGF-I levels in the vaste majority of patients. Octreotide is also effective in ameliorating TSH-induced hyperthyroidism in patients with TSH-secreting adenomas. Moreover, octreotide has proved useful in the management of endocrine tumours of the gastroenteropancreatic tract (vipomas, glucagonomas, gastrinomas, insulinomas, and carcinoids) by reducing hormone levels and in some instances the size of the primary and/or metastatic lesions. Besides the above well-established indications there are some other potential indications (non-secreting pituitary tumours, medullary thyroid carcinoma, ectopic Cushing's syndrome, diabete mellitus, Graves' ophthalmopathy, tall children and polycystic ovary syndrome) that still await further investigation. Side-effects of octreotide, particularly the formation of gallstones, should be carefully monitored.
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PMID:[Therapeutic use of somatostatin analogues in endocrinology]. 136 50

The use of somatostatin to manage diarrhea associated with the short gut syndrome is impractical because of its need to be given by continuous infusion and a rebound effect on stool output with cessation of therapy. Octreotide has been used more successfully to control stool and electrolyte losses in patients with shortened gastrointestinal tracts. In published series and studies, all subjects appear to decrease stool losses, but clinical benefit for long-term use is not achieved for all patients. In the patients who do respond, the need for parenteral nutrition and intravenous hydration has been decreased or eliminated. The optimal dose is unclear, but many patients respond to 50-micrograms injections twice daily. Several investigations noted no additional beneficial effects with escalating dosages. Adverse effects include impairment of fat absorption, which may offset the therapeutic benefits of octreotide. The patients with the greatest response appear to have the least fat malabsorption. Other adverse effects noted when using octreotide for control of the short gut syndrome include pain associated with subcutaneous injection and abdominal complaints. Other potential concerns include the effect on gallstone formation in this high-risk population and intestinal adaptation.
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PMID:Somatostatin and its analogs in the short bowel syndrome. 136 86

The increased risk of gallstone formation in acromegalics treated with the somatostatin analog octreotide has been related to an impaired gallbladder emptying. To determine the duration of these inhibitory effects, meal-stimulated gallbladder motility, plasma cholecystokinin (CCK), and pancreatic polypeptide (PP) were measured in five acromegalics treated for 6-32 months with 200-300 micrograms octreotide daily. Meal tests were performed 45 min, 8 hr and two weeks after the last 100-micrograms subcutaneous dose. Results were compared with those in normal subjects. Integrated postprandial gallbladder contraction (-125 +/- 194 cm3/120 min) and integrated PP secretion (-0.1 +/- 0.2 nmol/liter/120 min) were completely suppressed in the 45-min study, but significantly improved (P < 0.05) when measured 8 hr (1376 +/- 322 cm3/120 min and 3.0 +/- 1.0 nmol/liter/120 min) and two weeks (1437 +/- 263 cm3/120 min and 10.6 +/- 1.6 nmol/liter/120 min) after the last dose of octreotide. The integrated gallbladder contraction in acromegalics at 8 hr was comparable to that at two weeks and to that in normal subjects, but the integrated PP response at 8 hr was significantly smaller (P < 0.05 vs two weeks and vs normals). Integrated plasma CCK secretion at 45 min (0.13 +/- 0.06 nmol/liter/120 min) was not statistically significantly different from the response at 8 hr (0.15 +/- 0.02 nmol/liter/120 min) and from that in normal subjects, but it was significantly increased at two weeks after cessation of octreotide (P < 0.05 vs 45 min and 8 hr).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Postprandial gallbladder motility and plasma cholecystokinin at regular time intervals after injection of octreotide in acromegalics on long-term treatment. 142 66

Long-acting somatostatin analogues are extensively used for the treatment of acromegalic patients who have not been cured by surgery or for whom surgery is contraindicated or hazardous. Such an analogue, Sandostatin, has been approved for this indication in various countries and to date an overall review is feasible. From the literature and our experience, clinical response of acromegaly is attained in 60% to 70%, with mainly a reduction in headaches, arthralgias, and acral growth. Hormonal response, evaluated on plasma growth hormone (GH) levels, is observed in more than 80% of the patients. In 36% to 45% of the patients, plasma GH levels are reduced to near-normal values, and in 50% of the patients, the percentage of reduction is greater than 50% of pretreatment values. The major source of concern is the occurrence of gallstones during the treatment; its frequency is evaluated differently. From the largest well-documented series, we retain a percentage of 12.5% of newly occurring cholelithiasis and in most cases they remain asymptomatic. Tumor shrinkage is minor in most cases.
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PMID:The role of Sandostatin in acromegaly. 151 32

Twenty-five acromegalic patients were studied during 6 years of treatment with octreotide, with a particular focus on the following parameters: (1) Administration schedule: in 10 patients, continuous subcutaneous (SC) octreotide infusion was compared with injections of octreotide at three dose levels (100, 250, and 1,500 micrograms/24 h) and was found to induce a greater and less-fluctuating 24-hour growth hormone (GH) suppression. (2) Carbohydrate tolerance: average 24-hour blood glucose levels were unaffected by octreotide, regardless of administration schedule. Oral carbohydrate tolerance and intravenous (IV) glucose tolerance were unaffected by continuous octreotide infusion. However, octreotide injection given shortly before the tests reduced carbohydrate tolerance. (3) Thyroid function: octreotide and somatostatin acutely reduce the response of thyroid-stimulating hormone (TSH) to thyrotropin-releasing hormone (TRH). After a few days of treatment, it was demonstrated that octreotide slightly inhibits iodothyronine deiodination and induces a transient reduction in serum triiodothyronine (T3), rapidly compensated for by a persistent slight elevation of serum TSH. (4) Fat absorption was estimated as 24-hour fecal fat content and found to be in the same high-normal range before and after octreotide treatment. Vitamin K and D absorption were unaffected by octreotide. The incidence of gallstone formation was not greater than in the general Danish population, possibly due to the schedule used for octreotide injections. (5) Foot volume was regularly estimated and found to decrease with time, on average by 12% during the first 18 months.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Long-term efficacy and tolerability of octreotide treatment in acromegaly. 151 33

Practical approaches to the management of acromegaly are discussed. The roles of surgery, radiotherapy, and medical treatment with oral dopamine agonists such as bromocriptine or the long-acting somatostatin analogue octreotide given subcutaneously are reviewed. Most cases need surgery, but cure is rare in patients with macroadenomas, although common with microadenomas. Radiotherapy should be considered in surgical failures, but takes several years to be effective. Medical treatment with octreotide is effective in the majority, for whom it represents a major advance, but it needs to be administered subcutaneously and the development of gallstones and gastritis in long-term treatment are problems. Bromocriptine is usually less effective, but occasionally still plays a role in the therapeutic program. Combinations of the different modalities are usually required in the management of acromegalic patients.
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PMID:Proceedings of the workshop, "Practical approaches to the diagnosis and treatment of acromegaly". 151 40

Somatostatin and its synthetic analogue, octreotide, inhibit gallbladder emptying and cause gallstones. Whether octreotide-induced alterations in sphincter of Oddi motility contribute to this process is unknown. We, therefore, examined the effect of octreotide on fasting and protein-stimulated sphincter of Oddi motility. In 25 anesthetized prairie dogs, sphincter of Oddi motility and gallbladder pressure were monitored during the intravenous administration of octreotide, cholecystokinin (CCK) octapeptide, atropine, the intraduodenal administration of casein, and combinations of these agents. Intravenous octreotide decreased fasting sphincter of Oddi motility index both with (59 +/- 19 vs. 84 +/- 28, P less than 0.05) and without (137 +/- 31 vs. 227 +/- 42, P less than 0.05) prior cholinergic blockade with atropine. Octreotide also prevented the increases in sphincter of Oddi motility and gallbladder pressure seen with intraduodenal casein. Exogenous CCK increased sphincter of Oddi motility index and gallbladder pressure despite the simultaneous administration of octreotide alone (357 +/- 109 vs. 137 +/- 31, P less than 0.07, and 11.2 +/- 1.0 mmHg vs. 9.6 +/- 0.6 mmHg, P less than 0.05) or the combination of octreotide and atropine (317 +/- 69 vs. 59 +/- 19, P less than 0.05, and 10.1 +/- 1.6 mmHg vs. 8.5 +/- 1.4 mmHg, P less than 0.05). We conclude that both a cholinergic and an octreotide-sensitive noncholinergic pathway stimulate fasting sphincter of Oddi motility in the prairie dog.
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PMID:Effect of octreotide on sphincter of Oddi and gallbladder motility in prairie dogs. 159 Mar 99

Twenty-one patients with active acromegaly and two patients with pituitary gigantism were treated with the long-acting somatostatin analogue octreotide (100-600 micrograms/day, sc, two or three times daily or 300-1500 micrograms daily by intermittent sc infusion) for 9-63 months. There was rapid clinical improvement. The fasting plasma GH levels were significantly suppressed (less than 50% of the values before treatment) in 17 patients and were normalized (less than 5 ng/ml) in 6 patients (27.3%). Plasma IGF-I levels were lowered by 50% and were normalized in 7 out of 18 cases. The effect of octreotide on pituitary tumor size was evaluated in 13 patients. In 4 cases, the shrinkage of the pituitary tumor was detected by computed tomographic scans and/or magnetic resonance imaging studies. The drug was generally well tolerated. However, there were probably newly formed gallstones in two patients during the therapy. Our study suggests that octreotide is an effective and relatively safe new approach for treating active acromegaly and gigantism.
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PMID:[Long-term treatment of acromegaly and gigantism with octreotide (SMS 201-995)]. 159 44


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