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 may be due to various pathologic processes, but the majority of patients harbor a GH-producing pituitary tumor. Careful clinical, biochemical, and radiologic assessment is needed before designing an appropriate therapeutic plan. Treatment options include surgery, irradiation, dopamine agonists, and somatostatin analogues. Indications, limitations, and side effects of each modality are discussed.
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PMID:Acromegaly. Diagnosis and therapy. 266 76

To determine whether sc injections of a somatostatin analog (SMS 201-995) every 2 h (q2h) is more effective than sc injections every 8 h (q8h) in achieving a constant suppression of GH levels and a more satisfactory clinical response, we studied 10 patients with acromegaly (4 newly diagnosed and 6 previously treated with bromocriptine/pituitary irradiation/transfrontal hypophysectomy). The dose of SMS 201-995 was increased from 300 micrograms/day to a maximum of 600 micrograms/day when the mean serum GH (hourly samples for 12 h) failed to be suppressed to undetectable levels in over 75% of the samples. Five patients received a 200-micrograms sc injection q8h (600 micrograms/day), and the other 5 received sc injections q2h [418 +/- 46 micrograms/day (mean +/- SE); range, 288-504 micrograms/day]. In the group receiving q2h sc SMS 201-995 there was a marked suppression of mean GH from a basal level of 77.3 +/- 24.7 mU/L to less than 5 mU/L in all five subjects. In the group receiving q8h sc SMS 201-995, mean GH was suppressed from a basal level of 82.2 +/- 21.7 to 15.4 +/- 3.3 mU/L after 6 months of therapy, and none of the patients had a mean GH level consistently less than 5 mU/L. Despite the difference in the level of GH suppression, mean serum somatomedin-C levels were decreased promptly in both groups of subjects. Associated with the decrease in somatomedin-C levels there was a marked clinical response in both groups, but improvement in clinical features and decreases in hand volumes and ring size occurred earlier in the group receiving SMS 201-995 q2h. Significant tumor shrinkage (25% to greater than 50% reduction) was observed in two patients receiving q2h injections, while a 25-50% reduction in tumor size was noted in another patient receiving q8h injections. Because of the small doses of SMS 201-995 used side-effects of abdominal discomfort and flatulence were mild and rapidly disappeared. Our results show that increasing the frequency of sc administration of the somatostatin analog from q8h to q2h leads to more marked and consistent suppression of GH levels and more rapid improvement of clinical signs. Increasing the frequency of delivery of SMS 201-995 may be an alternative to increasing the dose in some patients with acromegaly.
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PMID:Comparison of the effectiveness of 2-hourly versus 8-hourly subcutaneous injections of a somatostatin analog (SMS 201-995) in the treatment of acromegaly. 266 25

Sixty-four patients with active acromegaly and three patients with gigantism were treated with the long acting somatostatin analog SMS 201-995 (50-500 micrograms, sc, every 6-12 h or 150-880 micrograms daily by intermittent sc infusion, for up to 114 weeks). The fasting plasma GH levels were significantly suppressed (less than 50% of the values before treatment) in 49 patients and became normal in 18 patients. Suppression of GH secretion was associated with normalization of plasma somatomedin-C levels (14 out of 30 cases) and significant clinical improvement such as disappearance of headache and decrease of excessive sweating. Shrinkage of pituitary tumors as determined by computed tomography and/or magnetic resonance imaging studies occurred in 11 out of 40 cases. Side effects were minimal and tolerable. SMS 201-995 appears to be an effective agent for the treatment of acromegaly and gigantism.
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PMID:[A multicenter clinical trial of SMS 201-995 (octreotide acetate) in acromegaly and gigantism]. 268 94

The recommended dosage schedules for intermittent sc therapy with the somatostatin analogue octreotide in acromegaly vary widely, from 100 to 1500 micrograms daily. As acute administration of octreotide has been shown to predict its long-term response, we performed a single-dose response study in 5 patients with active acromegaly using doses of 25, 50, 100, 200 and 400 micrograms octreotide as well as a placebo injection. Plasma GH of 2 patients did not normalize after any of the injections, but nadir plasma GH overall gradually decreased as doses were increased from 25 to 400 micrograms. The 400 micrograms octreotide dose was superior with regard to the duration of plasma GH suppression to below 5 micrograms/l or 25% of the basal GH level, the mean GH as a percentage of the basal level over the first 4 and 8 h, and the integrated reduction of plasma GH during the first 4 and 8 h. The postprandial integrated insulin secretion during the first 3 h after injection of the octapeptide was significantly lower after 50, 100 and 400 micrograms than after the placebo injection. The mean plasma glucose as a percentage of the basal level during the first 8 h was significantly higher after octreotide after the 200 and 400 micrograms injections. Minor adverse events were seen in 2 patients after injection of 200 and 400 micrograms octreotide. Within the limitations of this single-dose response study it was concluded that injection of 400 micrograms octreotide yields the best results with regard to suppression of GH secretion, whereas the 50, 100 and 200 micrograms doses are superior to 25 micrograms, but do not differ from each other.
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PMID:Single-dose response study of the somatostatin analogue octreotide in acromegaly. 268 31

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

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

The effects on gallbladder motility of long term treatment with the somatostatin analog SMS 201-995 (SMS) were studied in five patients with acromegaly treated for 6-32 months with 200-300 micrograms SMS daily. SMS (100 micrograms) or placebo was injected sc 45 min before a standard breakfast. Gallbladder volume (ultrasonography), plasma cholecystokinin (CCK), and pancreatic polypeptide (PP) were measured until 120 min after the meal. SMS completely suppressed the postprandial gallbladder contraction, despite a blunted, though still statistically significant, increase in plasma CCK from 1.6 +/- 0.2 pmol/L to an average of 3.7 +/- 1.7 pmol/L (P less than 0.01). The postprandial plasma PP peak after placebo was replaced by a slight but statistically significant decrease after SMS (P less than 0.05). A statistically significant correlation between the plasma CCK values and corresponding gallbladder volumes was seen only after placebo injection, not in the SMS study. We conclude that during long term treatment of acromegalics with SMS, an injection of 100 micrograms, sc, completely abolishes gallbladder contraction for at least 2 h after a standard breakfast, despite blunted, but still significant, CCK release. The data suggest a decreased sensitivity of the gallbladder to endogenous CCK during long term treatment with SMS. Careful control of patients with respect to the formation of gallstones is recommended.
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PMID:Postprandial gallbladder motility during long term treatment with the long-acting somatostatin analog SMS 201-995 in acromegaly. 276 Jan 70

In an attempt to characterize GH and PRL secretion in acromegaly, the effects of various stimuli on GH and PRL release by cultured pituitary adenoma cells derived from acromegalic patients were studied. In addition, the PRL responses of somatotroph adenoma cells were compared to those of prolactinoma cells. GH-releasing hormone-(1-44) (GHRH) consistently stimulated GH secretion in all 14 somatotroph adenomas studied in a dose-dependent manner. The sensitivity as well as the magnitude of the GH responses to GHRH were highly variable in individual tissues. Somatotroph adenomas that did not respond to dopamine were more sensitive and had greater GH responses to GHRH. In 8 of 9 somatotroph adenomas that concomitantly secreted PRL, the addition of GHRH likewise increased PRL release. Omission of extracellular Ca2+ blocked the stimulatory effect of GHRH on GH and PRL secretion. When cells were coincubated with 0.1 nM somatostatin, GH and PRL secretion induced by 10 nM GHRH were completely blocked in most adenomas. Similarly, coincubation of dopamine resulted in inhibition of GHRH-induced hormone secretion in some adenomas. Addition of TRH to the incubation medium, on the other hand, significantly stimulated GH secretion in 8 of 14 adenomas, while TRH stimulated PRL release in all of the adenomas. Vasoactive intestinal peptide (VIP) and corticotropin-releasing hormone (CRH) produced an increase in GH and PRL secretion in other adenomas. In prolactinoma cells, somatostatin and dopamine unequivocally suppressed PRL secretion; however, other stimuli including GHRH, VIP, and CRF were ineffective. TRH induced a significant increase in PRL secretion in only one prolactinoma. These results suggest that responsiveness to GHRH and somatostatin is preserved in somatotroph adenomas; the responsiveness to GHRH is inversely correlated to that to dopamine; and PRL cells associated with somatotroph adenomas possess characteristics similar to those of GH cells. Further, the GH stimulatory actions of TRH and VIP are different.
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PMID:Effects of hypophysiotropic factors on growth hormone and prolactin secretion from somatotroph adenomas in culture. 285 94

Ten patients with active acromegaly received synthetic human pancreatic GH releasing factor (hpGHRF-44), and the GH responses to GHRF were compared with the basal GH levels and with the GH responses to arginine, TRH, LH-RH, somatostatin, and L-dopa. There were no significant relationships between the plasma GH responses to GHRF and the results of the stimulatory and inhibitory tests mentioned above, except that the responses to GHRF showed weak positive or negative correlations with the responses to LH-RH (r = +0.56) or with the basal GH levels (r = -0.57). These results indicate that acromegalic somatotrophs would have GHRF receptors as well as several other receptors to hypothalamic hormones and to dopamine, and that there might be no distinct relationship between the somatotroph sensitivities to GHRF and to other stimulatory or inhibitory stimuli. Further studies are required regarding the weak correlations between the response to GHRF and that to LH-RH or basal GH value.
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PMID:Comparative study on the responses of plasma GH to synthetic GH-releasing factor and other stimulatory and inhibitory agents in patients with acromegaly. 285 72

[125I-Tyr]Somatostatin [( 125I-Tyr]SRIH) binding was found in 11 GH-secreting pituitary adenomas [Kd = 0.46 +/- 0.15 (+/- SE) nM; maximum binding, 165 +/- 35 fmol/mg protein). This binding was specific, since it was displaced by somatostatin-14 (SRIH-14), N-Tyr-SRIH-14, and SRIH-28. In contrast, a number of peptides and drugs not structurally related to SRIH, such as bombesin, dopamine, LHRH, met-enkephalin, naloxone, neurotensin, secretin, substance P, TRH, or vasoactive intestinal peptide, did not affect [125I-Tyr]SRIH binding. [125I-Tyr]SRIH specific binding also was found in PRL-secreting pituitary adenomas. The kinetic characteristics of the specific binding were similar to those of GH-secreting adenomas. However, maximal binding was one quarter that of GH-secreting adenomas (37 +/- 9 fmol/mg protein). In contrast, nonsecreting (chromophobe) tumors were devoid of any specific binding. Finally, in acromegaly, the density of [125I-Tyr]SRIH-binding sites in the adenomas was negatively correlated with plasma GH levels before surgery (r = -0.80). This suggests that somatostatinergic control is involved in GH secretion in acromegalic patients.
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PMID:Somatostatin receptors in human growth hormone and prolactin-secreting pituitary adenomas. 286 Jan 20


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