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

Conventional surgery and radiotherapy for acromegaly have limitations. There are few data on the use of the somatostatin analog octreotide (Oct) as primary medical therapy. An open prospective study of 27 patients with newly diagnosed acromegaly was conducted in nine endocrine centers in the United Kingdom. Twenty patients had macroadenomas, and 7 had microadenomas. For the first 24 wk (phase 1), patients received sc Oct in an initial dose of 100 microg, 3 times daily, increased to 200 micro g three times daily after 4 wk in the 13 patients whose mean serum GH remained greater than 5 mU/liter (2 microg/liter). Five-point GH profiles were performed at 0, 4, 12, and 24 wk, and high resolution pituitary imaging using a standard protocol was performed at 0, 12, and 24 wk (magnetic resonance imaging in 25 patients and computed tomography in 2). Tumor dimensions and volumes were calculated by a central, reporting neuroradiologist, and the results were audited by a second, independent neuroradiologist. After 24 wk, 15 patients proceeded to phase 2 of the study with a direct switch to monthly injections of the depot formulation of Oct, Sandostatin long-acting release (Oct-LAR). Further GH profiles were performed at 36 and 48 wk, and pituitary imaging was performed at 48 wk. The median pretreatment serum GH concentration was 30.7 mU/liter (range, 6.7-141.4). During sc Oct, serum GH fell to less than 5 mU/liter in 9 patients (38%), and IGF-I fell to normal in 8 patients (33%). All 27 tumors shrank during sc Oct; for microadenomas the median tumor volume reduction was 49% (range, 12-73), and for macroadenomas it was 43% (range, 6-92). After 24 wk of Oct-LAR (end of phase 2), the GH level was less than 5 mU/liter in 11 of 14 patients (79%), and IGF-I was normal in 8 of 15 patients (53%). In the 15 patients given Oct-LAR (10 macroadenomas), wk 48 scans showed a further overall median tumor volume reduction of 24%. At the end of the study 79% of patients had mean serum GH levels below 5 mU/liter, 53% had normal IGF-I levels, and 73% showed greater than 30% tumor shrinkage. Twenty-nine percent of patients achieved all 3 targets, but no patient with pretreatment GH levels above 50 mU/liter did so at any stage of the study. Primary medical therapy with Oct offers the prospect of normalization of GH/IGF-I levels together with substantial tumor shrinkage in a significant subset of acromegalic patients. This is most likely to occur in patients with pretreatment GH levels less than 50 mU/liter (20 microg/liter).
 ...
PMID:Primary medical therapy for acromegaly: an open, prospective, multicenter study of the effects of subcutaneous and intramuscular slow-release octreotide on growth hormone, insulin-like growth factor-I, and tumor size. 1236 34

The medical therapy for advanced or metastatic medullary thyroid carcinoma has not been fully established. Somatostatin analogs have been used with variable success in the therapy of a few patients with medullary thyroid carcinoma. In the present study, we evaluated the effects of somatostatin analog therapy on calcitonin (ct) and carcinoembryonic antigen in patients with advanced medullary thyroid carcinoma. Five patients (2 men and 3 women, aged 35-57 yr) with post-operative recurrent medullary thyroid carcinoma received somatostatin analog therapy for 12 weeks. All had been previously treated with total thyroidectomy and lymphadenectomy. Four of them showed positive uptake in (111)In-pentetreotide scanning. One patient was treated with sc octreotide (100 microg/8 h), 3 patients received im slow release lanreotide (30 mg/14 days), and a further one received im octreotide LAR (30 mg/28 days). Serum samples for ct and carcinoembryonic antigen were obtained at 0, 1, 2, 4, 8 and 12 weeks of therapy. Therapy was well-tolerated in general, with minimal side-effects. One patient died after the first month of therapy because of advanced disease. Another patient showed normalization of his ct and carcinoembryonic antigen concentrations at the second week of therapy, maintaining elevated values thereafter. No clinically relevant changes in serum concentrations of ct and carcinoembryonic antigen were observed in the rest of the patients. One patient with positive (111)In-pentetreotide scan, showed no uptake after somatostatin analog therapy. No significant decrease in the size of metastases was evident in the remaining patients. In conclusion, therapy with different formulations of octreotide and lanreotide does not seem to modify serum concentrations of ct and carcinoembryonic antigen in patients with recurrent medullary thyroid carcinoma.
 ...
PMID:Somatostatin analogs in the treatment of medullary thyroid carcinoma. 1239 35

Glucagonomas are rare tumors originating in alpha-cells of the pancreas. The most common clinical presentation is the association of diabetes mellitus, necrolytic erythema, weight loss and anemia. The diagnosis of pancreatic tumor is usually made by abdominal computed tomography and/or endoscopic ultrasonography. Indium-labeled octreotide scanning is useful for the localization of most neuroendocrine tumors and their metastases. Glucagon release can be confirmed by a high concentration of plasma glucagon. We report the case of a 74-year-old patient who had a glucagonoma with particular presentation of neurological impairment and weight loss. The diagnosis was confirmed by usual imaging procedures and plasma glucagon level. Medical treatment was started with long-acting repeatable octreotide (Sandostatin(R) LAR). After a one-year follow-up, the patient remained well. The original presentation and benefit of a new, long-acting somatostatin analog for the treatment of inoperable glucagonoma are discussed.
 ...
PMID:[Clinical response of an atypical glucagonoma treated with a long-acting somatostatin analog]. 1243 3

A diabetic acromegalic man, not cured after surgery and radiosurgery, received lanreotide i.m. with great clinical and biochemical improvement. He required NPH insulin (76 to 84 units/day) to control his diabetes mellitus. Thirty-six hours after changing to LAR-octreotide (20 mg i.m/month) he presented symptomatic hypoglycemia, repeated at 48 and 72 h (50 mg/dL), despite reducing insulin to 26 Units/day. Thereafter, he reduced insulin by 30 to 50% for the first week after each LAR-octreotide injection, and gradually increased it again over the next 3 weeks. This situation persists after every injection 3 years later; this consistent behavior supports a specific effect of LAR-octreotide, and not a by chance phenomenon. No marked changes in circulating GH, IGF-1, immunoreative insulin, C-peptide, testosterone and glucose were observed prior to, and 3, 7, 14, 21, and 28 days after LAR-octreotide; however, there was 28% fall in plasma glucagon after 7 days, which rose thereafter. C-peptide (< 1.8 ng/mL) was indicative of decreased beta-cell function. To our knowledge, this is the first report of such a distinct differential behaviour of blood glucose and insulin requirements with different somatostatin analogs, and is worth recalling when starting an insulin-treated diabetic patient on this treatment. It may be related to a preferential binding of LAR-octreotide to subtype 2 somatostatin receptors in the pancreas, while lanreotide preferentially binds to subtype 5, not expressed in this tissue; this would explain the fall in glucagon, in parallel to the decrease in insulin requirements after LAR-octreotide; however, a contribution of differences in the effect of both somatostatin analogues on postreceptor signalling systems and/or intestinal carbohydrate absorption cannot be entirely ruled out.
 ...
PMID:Decreased insulin requirements after LAR-octreotide but not after lanreotide in an acromegalic patient. 1250 80

The primary treatment of acromegaly remains transsphenoidal adenomectomy, yet the tissue overgrowth of acromegaly often progresses following surgery, and responds to radiotherapy only after significant delay. Persistently elevated serum growth hormone (GH) and insulin-like growth factor-I (IGF-I) concentrations can be normalized in about half of post-surgery acromegalics using the pharmacologic alternatives presently available, the dopamine agonists (DA) and somatostatin (SST) analogs. Cabergoline, the most efficacious DA, normalizes IGF-I in approximately 37% of patients, whereas the long-acting SST analogs, Octreotide LAR and Lanreotide SR, do so in 66%. Significant tumor shrinkage may be attained with SST analogs in particular, and when necessary, the primary medical treatment of acromegaly may be successfully addressed with this class of drugs. Greatly enhanced efficacy is expected from the GH receptor antagonist pegvisomant, which is nearing market availability and will enable the normalization of serum IGF-I in virtually all patients treated. We review here the pharmacologic treatments of excessive GH secretion.
 ...
PMID:Medical management of growth hormone-secreting pituitary adenomas. 1267 3

Although acromegaly remains a disease primarily addressed by pituitary microsurgery, most patients require secondary treatment for persistent growth hormone (GH) hypersecretion and elevated serum insulin-like growth factor-1 (IGF-1) concentrations following adenomectomy. Persistently abnormal serum GH and IGF-1 can be reduced to normal concentrations in better than half of post-surgery acromegalics using the pharmacologic treatments available at present, the dopamine agonists (DA) and somatostatin (SST) analogs. The long-acting SST analogs octreotide LAR and lanreotide SR have become the mainstay of medical treatment for acromegaly, having largely supplanted DA agents since the introduction of bromocriptine for the suppression of GH secretion in the 1970s. The DA cabergoline may be effective in up to half of patients, however, in particular those patients whose tumors cosecrete prolactin. On the horizon is the GH-receptor antagonist pegvisomant, which is expected to enable the reduction of serum IGF-1 to the normal range in the vast majority of postoperative acromegaly patients, representing a revolutionary development in the medical treatment of this disease. We here review the choices available to the endocrinologist in the pharmacologic treatment of acromegaly, focusing upon the SST analogs.
 ...
PMID:Somatostatin analogs in medical treatment of acromegaly. 1272 7

Many studies have recently shown that simple computer-solved indices, based on fasting glucose and insulin levels, closely mirror the euglycemic clamp technique in studying insulin resistance or pancreatic insulin secretion. Few data are at present available on the evaluation of these novel indices in acromegalic patients, known to be GH-dependent insulin-resistant subjects, in particular during medical treatment with somatostatin analogues. Indeed, these drugs are able to inhibit not only GH and IGF-I levels, but also insulin and glucagon pancreatic secretion, with contrasting effects on glucose metabolism. In this study, insulin resistance was evaluated by the homeostasis model assessment (HOMA-IR) and insulin sensitivity by quantitative insulin check index (QUICKI) in 27 normoglycemic acromegalic patients, before and after 6-month therapy with somatostatin analogues (lanreotide-SR 30-60 mg every 7-28 days in 15 and octreotide-LAR 20-30 mg every 28 days in 12). Thirty-five age- and sex-matched healthy subjects and 17 surgically treated acromegalic patients (5 cured and 12 not cured) were studied as control groups. Before medical treatment, HOMA-IR was higher in acromegalic patients than in healthy controls (4 +/- 3 vs 1.7 +/- 0.7, p < 0.05), while QUICKI was lower (0.33 +/- 0.04 vs 0.36 +/- 0.03, p < 0.05). During medical therapy, HOMA-IR decreased to 2.4 +/- 1.6 (p < 0.05) and became similar to that recorded in both healthy subjects and surgically treated patients. However, fasting glucose was increased and fasting insulin was decreased. QUICKI did not significantly change from basal values. No differences were observed between patients who normalized or not hormonal levels. The effects of the 2 drugs, though higher glucose levels were seen in patients treated with octreotide-LAR. In conclusion, this study demonstrates that medical treatment is able to improve insulin resistance, even if only successful surgery is able to completely normalize both HOMA-IR and QUICKI.
 ...
PMID:Evaluation of insulin resistance in acromegalic patients before and after treatment with somatostatin analogues. 1295 67

Cushing's syndrome (CS) due to ectopic ACTH secretion (EAS) has a high morbidity and mortality, because of the underlying tumor and the sequelae of severe hypercortisolemia. Therefore, rapid treatment of ectopic CS is mandatory. Scintigraphy shows that up to 80% of ectopic ACTH-producing tumors have somatostatin receptors. While this suggests that somatostatin analogs may reduce ACTH production and treat patients with EAS, the therapeutic role of these agents is still evolving. Here we demonstrate the spectrum of responses to octreotide therapy in 3 patients with EAS. Diagnostic imaging with the 111In-pentetreotide scan did not predict the therapeutic response to octreotide. Two patients with positive somatostatin receptor scintigraphy failed to respond to octreotide, while one with a negative scan reached eucortisolemia on a maintenance dose of 75 microg octreotide twice daily or octreotide LAR 30 mg per month. We conclude that octreotide is not a first line agent to control hypercortisolemia but may be a useful agent when other inhibitors of steroidogenesis fail or parenteral administration is required. Before therapy an octreotide challenge test may predict therapeutic response. Cortisol levels should be monitored regularly on somatostatin analog therapy, because of its unpredictable long-term pharmacodynamic profile.
 ...
PMID:Is there a therapeutic role for octreotide in patients with ectopic Cushing's syndrome? 1466 23

Octreotide is a somatostatin analog that inhibits growth hormone release showing higher potency than natural somatostatin so it has proved to be effective in acromegaly treatment. The objective of present study was to establish the effects of octreotide LAR (long acting release) preparation in patients with active acromegaly. The following parameters were assessed: clinical response, safety of medication, GH and IGF-1 serum concentrations and pituitary tumor size. Eleven patients (6 men and 5 women) range 41.4 years old with diagnosis of active acromegaly were included. Octreotide was administered at 0.1 mg subcutaneusly dose three times daily for four weeks to test the drug tolerability. Afterwards patients received octreotide LAR 20 mg intramuscularly separated by 28 days periods with an option to continue for 8 months. Basal average GH serum concentrations was 27.6 ng/mL. After 6 months treatment reduction to 5.03 +/- 5.38 ng/mL in 9 patients (p < 0.001) was observed. Basal IGF-1 average serum concentration was 889.55 +/- 167.29 ng/mL with a reduction value to 483.00 +/- 239.71 ng/mL in 9 of 11 patients after 6 months treatment (p < 0.005). The drug was well tolerated with few adverse effects Diarrhea, flatulence and steatorrhea were observed during the administration of subcutaneous octreotide in 18.2% of patients. Two patients had symptomatic biliary lithiasis that was successfully removed by surgery. Clinical symptoms improved and some of them dissapeared such as headaches and sweatings. Tumor shrinkage was observed in 66.7% of cases. Monthly injections of 20 mg of octreotide LAR were effective to reduce GH and IGF-1 levels in patients with active acromegaly accompanied by improvement of clinical symptoms and significant tumor size reduction.
 ...
PMID:Improvement of acromegaly after octreotide LAR treatment. 1467 21

In the last decade important progresses have been obtained in the diagnosis and therapy of endocrine gastroenteropancreatic (GEP) tumors, mainly derived from the somatostatin receptors characterization and the introduction of long acting somatostatin analogues. Receptorial scintigraphy with radio-labeled analogues (Octreoscan) is the first choice investigation for staging and follow-up of endocrine GEP tumors, thanks to the high sensitivity in revealing the primary tumor and metastases, and for its capability to reveal lesions that are not identified by other imaging methods. Moreover, somatostatin analogues uptake by tumors allow us to use radiopharmaceutical compounds for advanced disease treatment. Between the radio-labeled drugs until now studied, interesting results have been obtained by DOTA-lanreotide (MAURITIUS), DOTA0 Tyr3-octreotide (DOTATOC) and DOTA0 Tyr3-octreotate, bound to beta-emitting radio-isotope suitable for therapeutic use. In the field of the pharmacological therapy of GEP tumors, the clinical trials show that somatostatin analogues reduce the symptoms related to functionally active tumors and stabilize or slow tumor growth improving the patient quality of life. Although somatostatin analogues alone could not be able to cure GEP tumors, their early utilization in association with surgical debulking of primary tumor and metastases, embolization or chemoembolization, and interferon, chemotherapy and radio-metabolic therapy (mainly directed to the destruction of micrometastases), increases the possibility of a radical therapeutic intervention. The continuous evolution of pharmacological research provides always new analogues (octreotide LAR, lanreotide, vapreotide, BIM-23244, BN 81644, PTR-3173, BIM-23A387, SOM-230, etc.) with different pharmacokinetic and receptorial properties and acting with more effectiveness in the different individual clinical situations. In this context there have been recently introduced also the "chimeric" analogues. On the other hand, the widespread utilization of molecular biology and immunohistochemical methods can allow, in perspective, to better define the receptorial pattern of individual endocrine tumors, after their surgical removal. The necessity to integrate endocrinological, nuclear medicine, surgical, oncologic and laboratory competencies behaves a multidisciplinary approach based on the utilization of diagnostic-therapeutic protocols supplying comparable results. It does not appear unjustified to expect, in the future, a scenery of more "individual" and more effective therapies for patients affected by GEP tumours.
 ...
PMID:[New perspectives in diagnosis and therapy of endocrine gastroenteropancreatic (GEP) tumors with somatostatin analogues]. 1475 99


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>