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)

Acromegaly is a unique condition characterized by chronic growth hormone (GH) and insulin-like growth factor-1 (IGF-1) hypersecretion usually due to a pituitary adenoma. Rarely, acromegaly can result from a GH-releasing hormone carcinoid or pancreatic neoplasm which stimulates the normal pituitary to secrete GH. This review describes the interactions between acromegaly and the gastrointestinal system. In contrast to the soft tissue and skeletal changes, clinical organomegaly of the liver, kidney, and spleen is unusual in patients with acromegaly and should warrant further investigations. The prevalence of cholelithiasis is notably increased by the use of the otherwise effective GH-lowering somatostatin analog, octreotide. Patients on long-term therapy with this agent may require anticholelithogenic treatment. The frequency of malignant and premalignant polyps of the colon justify the routine screening for these lesions in newly diagnosed patients with acromegaly.
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PMID:Hepatobiliary and gastrointestinal manifestations of acromegaly. 161 13

The long-acting somatostatin analogue octreotide is a synthetic cyclic peptide consisting of 8 amino acids. Depending on the organ, it acts either as a hormone or as a neurotransmitter. The effect on various physiological functions in the brain and the gastrointestinal tract is mainly inhibitory. Due to its inhibitory actions, the possibility of intravenous and subcutaneous administration and the lack of serious side-effects, octreotide offers a broad spectrum of possible indications. Today octreotide is recommended in acromegaly patients and for the treatment of hormone dependent symptoms in patients with gastroenteropancreatic tumours. New indications are enterocutaneous and pancreatic fistulas and the prevention of complications in major pancreatic surgery. In patients with dumping and short-bowel syndrome, octreotide may be helpful until dietary regimens are established. In Aids patients with severe diarrhea, octreotide can be used to stabilize patients with severe dehydration and malnutrition. The clinical effectiveness on upper GI-bleeding due to gastric ulcer and oesophageal varices is still controversial. Future studies must prove whether octreotide may be helpful in treating diabetic retino- and nephropathy because of the possibility of suppressing growth hormone and IGF-I. The antiproliferative effect of octreotide also allows its use in patients with somatostatin-receptor-positive, non-endocrine solid tumors (e.g. brain, breast and small-cell lung cancer). A promising area is the scintigraphic visualization of somatostatin-receptor-positive tumors with a radio-labelled octreotide analogue and the possible target irradiation of these tumors by beta-particle emitting isotopes attached to such analogues.
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PMID:[Somatostatin analog (octreotide) in clinical use: current and potential indications]. 162 Oct 78

The development of gallstones is a well recognized complication of therapy with the long-acting somatostatin analogue, octreotide in patients with acromegaly. A group of nine acromegalic patients was treated with octreotide at doses of 300-600 micrograms daily for 8 months and the changes in fasting and post-prandial cholecystokinin release, and gall bladder motor function (determined by a radiosotopic technique) were assessed at regular intervals. In addition the development of any gallstones was determined by serial ultrasonography. Fasting cholecystokinin levels showed no significant change over 6 months, whereas the post-prandial levels demonstrated a significant decrease (p less than 0.01) during therapy, yet remained significantly higher than fasting levels. Twenty-four hours after commencing therapy gall bladder ejection fraction was decreased by 57 +/- 23 per cent and gall bladder ejection rate decreased by 63 +/- 19 per cent compared to the pretreatment values, whereas after 6 months' therapy a marked reduction in gall bladder ejection fraction (greater than 35 per cent) and gall bladder ejection rate (greater than 40 per cent) persisted in only four of nine patients. Three of these four patients with persistently impaired gall bladder motor function were subsequently shown to have developed either gallstones or biliary sludge during the course of therapy. We conclude that treatment with octreotide is associated with an impaired post-prandial release of cholecystokinin in all acromegalic patients, but gallstones only develop in those patients who, in addition, have evidence of a persistently impaired gall bladder motor response to cholecystokinin.
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PMID:Assessment of gall bladder dynamics, cholecystokinin release and the development of gallstones during octreotide therapy for acromegaly. 163 Dec 61

The recent availability of a Tyr3-substituted octreotide (SDZ 204-090) for radioiodination has allowed somatostatin (SRIH) receptor binding to be studied in vivo, and receptor-positive tumors of different origins to be visualized with a gamma-camera. This prompted us to investigate whether this compound could be used for external imaging of functionless pituitary adenomas displaying SRIH receptors. Eight patients with functionless pituitary adenomas, three patients with acromegaly, and three with macroprolactinoma were injected iv with 123I-labeled Tyr3-octreotide and then scanned with a gamma-camera. Positive scans were obtained in the three acromegalics and in two of the eight patients with functionless pituitary tumors. The patients with macroprolactinoma had negative scans. The diagnosis of functionless pituitary adenomas was confirmed by light and electron microscopic examination as well as immunocytochemical studies. In vitro binding of [125I]Tyr11-SRIH to cell membranes was evaluated in four functionless and three GH-secreting adenomas removed from seven of the patients. All of the GH-secreting as well as one of the four functionless adenomas had high affinity SRIH-binding sites, without differences in number or affinity, whereas SRIH-binding sites were not detected in the others. Positive scans were observed only in patients bearing tumors with high affinity SRIH-binding sites. In conclusion, [123I]Tyr3-octreotide appears to be a promising tool for singling out, in vivo, patients with functionless pituitary tumors displaying SRIH receptors who might potentially benefit from octreotide treatment.
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PMID:In vivo detection of somatostatin receptors in patients with functionless pituitary adenomas by means of a radioiodinated analog of somatostatin ([123I]SDZ 204-090). 165 85

The binding of 123I-Tyr-3-octreotide (SDZ-204-090; specific activity 1 mCi/nmol), a new somatostatin-receptor binding radiopharmaceutical, to human tumour membrane fractions was evaluated in presence of unlabeled Tyr-3-octreotide and octreotide (SMS-201-995; Sandostatin). Tumour tissue was obtained intraoperatively from 15 patients with different endocrine tumours (insulinoma, carcinoide, phaechromocytoma, hypophysal adenoma) and breast cancer. In equilibrium experiments, membrane fractions (200 micrograms protein/ml) were incubated with increasing concentrations of 123I-Tyr-3-octreotide (0.03-30 nM) in presence or absence of 5 microM of unlabeled agonist. Binding capacities ranged from 1-20 pmol/mg protein (Kd 4-100 nM). The IC50 values (2.5-112 nM versus 0.02-69 nM) were different for the octreotide and Tyr-3-octreotide indicating that octreotide was the better competitor as Tyr-3-octreotide for 123I-Tyr-3-octreotide binding sites. In ductal breast cancer high numbers of in vitro binding sites for the radiolabel were found. In initial clinical studies 123I-Tyr-3-octreotide was i.v.-injected (3 mCi) to 5 acromegaly patients with hypophyseal adenomas. Following rapid uptake by the liver, positive tumour imaging was obtained in 3 patients which correlated to computer tomographic findings. Positive images were obtained just some minutes after injection. Our results support recent data suggesting that the 123I-Tyr-3-octreotide would be a suitable receptor-radiopharmaceutical for the localization of endocrine tumours.
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PMID:Evaluation of somatostatin receptors in human cancer. 166

We report a patient with acromegaly who had severe, intractable headache unrelated to tumor size which dramatically resolved with the somatostatin analog octreotide. The analgesic effects of octreotide were neither related to significant inhibition of growth hormone nor influenced by naloxone. Our data suggest that octreotide should be considered in patients with intractable headache associated with pituitary adenomas. Mechanisms other than tumor size or interaction with the opioid system, such as non-opioid algesic peptide secretion, may be the explanation for severe head pain in some pituitary adenomas.
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PMID:Analgesic effect of octreotide in headache associated with acromegaly is not mediated by opioid mechanisms. Case report. 166 9

The role of dopaminergic agents (DA) in the regulation of growth hormone (GH) secretion was investigated in patients with untreated acromegaly. TRH (0.5 mg iv), bromocriptine (Br) (2.5 mg orally) or L-Dopa (500 mg orally) loading tests were performed, and serum levels of TSH, GH and prolactin (PRL) were measured. Patients were defined as responders to TRH when peak TSH level after TRH test was higher than 5 microU/ml. Br or L-Dopa was considered to be effective when serum GH or PRL levels were suppressed more than 50% of the basal value. The patients were classified into large adenoma group with suprasellar extension or cisternal herniation (L group, n = 7) and intrasellar small adenoma group (S group, n = 11) which was further divided into TRH responder (Sr group, n = 4) and TRH non-responder with suppressed TSH (Ss group, n = 7). Br was effective in 7 or 100% of 7 patients in the Ss group but only in one or 25% of 4 patients in the Sr group. Br was also effective in 5 or 71% of 7 patients in the L group, although most of them were responders to TRH. Percent inhibition of serum GH levels by Br was significantly higher in the Ss group (82.3 +/- 12.3%, p less than 0.001) and in the L group (64.7 +/- 20.5%, p less than 0.05) compared with that in the Sr group (29.3 +/- 21.6%). Suppression of serum GH level by L-Dopa was also observed in the Ss group. In contrast to the difference in the response of GH, serum PRL level was equally suppressed by Br or L-Dopa in each group. Suppression of TSH by administration of exogenous T4 had no effect on the GH suppression effect of Br in the Sr group. Considering the dual effects of DA to enhance growth hormone-releasing hormone (GHRH) secretion in the hypothalamus and to suppress GH secretion in the pituitary gland, these findings suggest that the paradoxical effect of DA to suppress serum GH level is observed when the hypothalamo-pituitary axis is disturbed mechanically by large adenoma in the L group or functionally in the Ss group probably due to enhanced secretion of somatostatin which suppresses TSH secretion and impairs the effect of GHRH.
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PMID:[The relationship between TSH response to TRH and GH response to dopaminergic agents in patients with acromegaly]. 167 20

Somatostatin octapeptide analogues have a longer half-life and are more potent than natural somatostatin (SS-14). Somatostatin analogues are presently approved for the treatment of gastrointestinal (GI) endocrine cancers such as carcinoids, vipomas and glucagonomas. They are also effective in the treatment of inoperable or relapsing acromegaly. Although symptomatic relief is marked and rapidly induced, the inhibitory effect on tumor growth is modest. However, prolonged stabilizations are frequent. Somatostatin analogues may have wider therapeutic indications. Somatostatin octapeptide analogues are also known to interact with growth factors such as epidermal growth factor and insulin-like growth factor, and have shown cytostatic activity in vitro and in vivo in various experimental models of breast, prostate, lung and GI cancers. Neuroendocrine tumors often express somatostatin receptors. Labelled analogues may be useful for tumor assessment and for the prediction of tumor response to therapy. The role of somatostatin analogues in the treatment of the most frequent cancers is currently under investigation.
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PMID:[Somatostatin analogs in oncology]. 168 67

Ectopic GHRH is a relatively uncommon cause of acromegaly, which should be differentiated from pituitary adenoma, in order to avoid damage to the pituitary gland from unnecessary interventions. We report here on a 66-year-old man with acromegaly due to a GHRH-secreting bronchial carcinoid tumour, who recovered completely following removal of the tumour. His hormonal status was studied before and after the operation. Basal GH, GHRH, IGF-I and PRL levels, as well as plasma GH response to glucose load and TRH administration were abnormal before the operation, and became normal thereafter. The somatostatin analogue SMS 201-995 was found to be a potent inhibitor of the ectopic GHRH and the GH secretion (greater than 500 to 42 ng/l and 15.4 micrograms/l to 0.8 microgram/l, respectively). The effect on GHRH proved to be due to direct effect of somatostatin on the tumour cells, as demonstrated in tissue culture studies. A mixed meal was found immediately to suppress GHRH levels without such an effect on GH secretion. We conclude that the neuroendocrine tests usually practised in acromegaly cannot differentiate between ectopic GHRH secretion and pituitary adenoma. High plasma GHRH levels may serve as a diagnostic test for excessive GHRH production, which is almost always ectopic. These high levels are suppressible by somatostatin and a mixed meal.
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PMID:Acromegaly due to ectopic growth hormone-releasing hormone secretion by a bronchial carcinoid tumour. Dynamic hormonal responses to various stimuli. 168 1

Insulin-like growth factors (IGFs) circulate in a complexed state with several binding proteins (BPs). Of these, IGFBP-1 is regulated by hormonal and nutritional factors. The somatostatin analogue, octreotide, has been used to effectively control hypersomaototropism in acromegaly. IGFBP-1 levels were measured by RIA in 17 acromegalic patients receiving octreotide. Serum hormone sampling was conducted hourly for 8 hr periods. Among 13 octreotide responders, mean pre-treatment basal GH, IGF-1, and IGFBP-1 levels were 19 +/- 5 micrograms/L, 1021 +/- 168 micrograms/L, and 36 +/- 8 micrograms/L respectively. One month following octreotide treatment, an acute subcutaneous injection (100 micrograms) maximally attenuated GH to 3 +/- 0.6 microgram/L (18% of control, P less than 0.03) and IGF-1 to 467 +/- 75 micrograms/L (46% of control, P less than 0.008) after 4 hrs. IGFBP-1 levels, however, were stimulated to 95 +/- 16 micrograms/L (297% of control, P less than 0.003) during the same time period. A significant increase in IGFBP-1 levels occurred within 2 hrs (158% of baseline, P less than 0.03), and was sustained until the 7th hr following injection. Insulin, a known suppressor of IGFBP-1, did not change during this time. Among the 4 octreotide non-responders, mean basal IGFBP-1 levels were 42 +/- 4 micrograms/L, and 4 hrs following octreotide administration IGFBP-1 was 40 +/- 7 micrograms/L. Octreotide induced a dynamic inverse relationship between circulating GH and IGFBP-1 levels (r = -0.73, P less than 0.001). The absence of IGFBP-1 changes in octreotide non-responders and the non-suppression of insulin in octreotide responsive patients, suggest a direct GH-mediated mechanism of IGFBP-1 regulation in octreotide treated patients with acromegaly. IGFBP-1 may be another useful marker in evaluating the response of acromegaly to octreotide treatment in patients who experience clinical benefit but equivocal GH and IGF-1 attenuation.
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PMID:Octreotide stimulates insulin-like growth factor binding protein-1 (IGFBP-1) levels in acromegaly. 171 20


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