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)

The medical treatment of pituitary adenomas has changed significantly over the past decade. Pharmacologic therapy for prolactinomas in the form of dopamine agonists has been available since the 1970s, and somatostatin analogues for treatment of growth hormone (GH)-secreting adenomas were introduced in the 1980s. However, the recent introduction of long-acting forms of these agents has markedly improved efficacy. Furthermore, long-acting somatostatin analogues also have utility in treating thyrotropin adenomas and a subset of adrenocorticotroph tumors. Limited clinical studies with long-acting dopamine agonists suggest that a subset of patients with GH, adrenocorticotroph, and gonadotropin/nonsecreting adenomas may also benefit from therapy with these agents. The introduction of a GH receptor antagonist in the 1990s has added to the pharmacologic armamentarium for treatment of acromegaly. In parallel with improved medical therapy, hormonal assays for assessing tumor activity have improved in sensitivity, necessitating new standards for treatment optimization. This article highlights some of these evolving new ideas and approaches to the pharmacologic management of pituitary adenomas.
 ...
PMID:Update on the medical management of pituitary adenomas. 1586 83

Understanding the mechanisms by which growth hormone (GH) interacts with its receptor has led to the design of compounds that function as GH receptor antagonists. One such compound has been conjugated to polyethylene glycol (PEG) to produce a drug, pegvisomant, which has been extensively investigated as a treatment for acromegaly. It was recently approved for clinical use in the US and will shortly be available on prescription in Europe. Studies have shown that the drug is able to normalize circulating levels of insulin-like growth factor-1 (IGF-1), the principal mediator of GH action, in 97% of patients with active acromegaly, as well as improve the symptoms and signs associated with GH excess. Serum IGF-1 levels have been used as the chief marker of efficacy of treatment with pegvisomant. The drug is able to achieve biochemical control in patients wholly or partially resistant to somatostatin analogs. Preliminary data suggests that pegvisomant may be a particularly suitable choice of medical therapy for patients with acromegaly and coexistent diabetes mellitus.
 ...
PMID:Clinical use of pegvisomant for the treatment of acromegaly. 1598 41

Previously surgery and irradiation were the only available procedures to treat patients with pituitary tumors. During the last few decades, novel drugs such as dopamine agonists and long-acting somatostatin analogs were developed and, an alternative medical therapy emerged. This paper summarizes the effect of medical therapy on the morphologic features of pituitary tumors and illustrates the ultrastructural alterations on electron micrographs. Currently drugs can be used in the management of pituitary tumors secreting GH, PRL, and/or TSH in excess. No medical therapy is available so far for ACTH-, FSH-, LH-, or alpha-subunit-secreting tumors as well as non-hormone-secreting pituitary tumors. Dopamine agonists are effective in the management of PRL-secreting tumors; they cause marked reversible tumor shrinkage in the substantial majority of patients. Long-acting somatostatin analogs are useful in the management of GH- and TSH-secreting pituitary tumors; they lead to mild to moderate tumor shrinkage in approximately 50% of cases. In patients treated with these drugs reduction of elevated blood hormone levels and amelioration of clinical symptoms ensue. It should be emphasized that no permanent cure is obtained. Blood hormone levels increase and the clinical symptoms reappear after discontinuation of treatment. Recently GH receptor blockers (pegvisomant) were introduced in the treatment of GH-producing pituitary adenomas. To the authors' knowledge the effect of these drugs on the morphology of pituitary tumors has not been revealed so far.
 ...
PMID:Effects of medical therapy on pituitary tumors. 1603 72

Recent progress in the therapy of GH-secreting pituitary tumors includes three treatment modalities: surgery, radiotherapy, and medications. A combination of treatment options is often required to attain therapeutic goals, increasing the potential for a combination of unwanted side effects. The focus of this review is to discuss medical therapy of GH-secreting adenomas focusing on newer drug compounds. In selected cases, therapeutic goals are attained with somatostatin analog treatment alone. The GH receptor antagonist controls IGF-I hypersecretion, and its use in combination with somatostatin analogs in selected patients is tempting but requires further evaluation. Somatostatin multireceptor ligand SOM230 and a somatostatin-dopamine chimeric ligand are new compounds that may improve therapy outcome. Careful individualization of therapy is important in deciding the ideal treatment approach, and primary medical therapy may be recommended in selected patients.
 ...
PMID:Treatment of acromegaly: future. 1631 19

Active acromegaly deteriorates the quality of life and shortens the life expectancy. Surgery is the first-line therapy in the majority of patients, followed by radiotherapy in unsuccessful cases. The surgery cure rate is only one half in the case of macroadenomas and it takes years before radiotherapy normalizes GH and IGF-I levels. In the interim, medical therapy is necessary. Second-generation dopamine agonists (cabergoline) are successful in about one third of patients, especially in those with lower basal IGF-I levels and with adenomas co-secreting prolactin. Somatostatin analogues octreotide and lanreotide are the gold standard of medical treatment - both are available in a form applicable as once-monthly injections. They successfully control disease activity in the majority of patients and induce tumour shrinkage in part of adenomas. Surgical debunking of macroadenomas improves the results of therapy with somatostatin analogues and it is not necessary to discontinue this therapy before radiotherapy. The potential of higher efficiency represent new analogues, binding not only to somatostatin receptor subtype 2, but also to subtype 5 and "dopastatins" that are able to bind both to the somatostatin and the dopamine D2 receptors. The advent of the GH receptor antagonist pegvisomant provides the possibility to normalise IGF-I in virtually every patient. Combined treatment with somatostatin analogues probably enables reduction from daily to weekly injections.
 ...
PMID:[Possibilities of medical treatment in acromegaly]. 1633 61

The objective of this study was to determine whether differences in mRNA levels of key pituitary genes that regulate GH production, pituitary development, and growth were present and/or associated with divergent body composition phenotypes observed between sheep from genetically divergent lean and fat selection lines. Real-time PCR transcription profiles for pituitary specific transcription factor 1, prophet of pit1, GH, GH receptor, GH secretagogue receptor, GHRH receptor, leptin receptor, and somatostatin receptors 1 and 2 were determined in pituitary tissue. There was a difference in the amount of both GH (P < 0.001) and GH secretagogue receptor (P < 0.001) mRNA between the selection lines (5 females and 5 males per line; 20 wk of age); the lean line had greater abundance than the fat line, irrespective of which endogenous control gene was used. The results obtained for GHRH receptor were equivocal but suggestive; there were greater GHRH receptor mRNA levels (P < 0.001) in the lean line using beta-2-microglobulin as the endogenous control but not when hypoxanthine phosphoribosyltransferase and glyceraldehyde-3-phosphate dehydrogenase were used. No difference in pituitary specific transcription factor 1, prophet of pit1, GH receptor, leptin receptor, or somatostatin receptors 1 and 2 mRNA concentration was observed between the lines. The greater abundance of GH mRNA in the pituitary somatotropes from genetically lean animals appears to be associated with increased levels of GH secretagogue receptor mRNA and possibly GHRH receptor mRNA. This suggests that the difference in GH secretion between the lines may be due to differences in the afferent signals, such as ghrelin and/or GHRH, arising from the hypothalamus, or as a result of differential pituitary sensitivity to these hormones.
 ...
PMID:Growth hormone and ghrelin receptor genes are differentially expressed between genetically lean and fat selection lines of sheep. 1642 60

At present, diabetic kidney disease affects about 15-20% of all Type 1 diabetic patients and 20-40% of all patients with Type 2 diabetes. Preclinical research performed over the past decade has suggested growth hormone (GH) and insulin-like growth factors (IGFs) to be involved in the pathogenesis of diabetic kidney disease. Data obtained in knock-out (KO) mice with GH receptor (GHR)/GH binding protein (GHBP) gene-disruption have shown that these animals are protected against diabetes-induced renal changes. Further, diabetic mice treated with either a longacting somatostatin analogue or a specific GHR antagonist (GHRA) showed normalization of the diabetes-associated renal hypertrophy and glomerular enlargement and most importantly also a lowering effect on the diabetes-induced rise in urinary albumin excretion (UAE), a marker of renal damage. Based on these experimental data future studies are warranted to characterize the clinical potential of GH-inhibitors (e.g. GHRAs) as drugs for the treatment of diabetic renal complications.
 ...
PMID:The role of growth hormone in the pathogenesis of diabetic kidney disease. 1644 87

We report on a patient with acromegaly who developed severe drug-induced hepatitis during combined treatment with the long-acting somatostatin-analog octreotide and the GH receptor antagonist pegvisomant. The hepatic enzyme disturbances normalized after discontinuation of pegvisomant. After rechallenge with monotherapy pegvisomant, however, the hepatic enzyme disturbances reappeared within a few weeks, indicating that most likely pegvisomant alone and not the long-acting somatostatin analog or the combination of these two drugs was responsible for this case of drug-induced hepatitis. Clinicians should be aware of this potential severe adverse drug reaction and therefore frequent control of hepatic enzymes is mandatory during treatment with pegvisomant.
 ...
PMID:Drug-induced hepatitis in an acromegalic patient during combined treatment with pegvisomant and octreotide long-acting repeatable attributed to the use of pegvisomant. 1672 38

We describe the first case of a 36 year-old male patient with a somatotropin and thyreotropin secreting pituitary adenoma, co-treated by a long-acting releasing somatostatin analog (Octreotide) and a GH receptor antagonist (Pegvisomant). The patient normalized his biological disease activity reflected by hormone levels but his tumor size remained unchanged as measured by MRI. The co-treatment was well tolerated and induced a synergic effect on IGF1 levels that allowed us to use low doses of both therapies.
 ...
PMID:An unusual somatotropin and thyreotropin secreting pituitary adenoma efficiently controlled by Octreotide and Pegvisomant. 1684 Sep 17

Acromegaly, a multisystemic disease resulting from excessive growth hormone (GH) and insulin-like growth factor-I (IGF-I) levels in adults, is associated with a two-to-threefold increase in mortality. The available treatment options (surgery, radiotherapy and medical treatment with somatostatin analogues or dopamine agonists) fail to achieve the currently accepted goals of therapy in a substantial number of patients. Pegvisomant, a newly developed GH receptor antagonist, represents a novel treatment modality for this disease. It binds with the GH receptor and induces internalization, but blocks receptor signaling events, thereby reducing IGF-I production. The two main published studies suggest that it is the most potent medical therapy with greater specificity, without being dependent on the tumour characteristics. However, apart from its high cost and the dilemmas raised concerning the appropriateness of using serum IGF-I concentrations as a marker of disease activity, it may also occasionally be associated with elevations in liver enzyme levels. Further studies are required to confirm its high success rates as well as to investigate the possibility of inducing an increase in the pituitary tumour size. Currently, pegvisomant is a second line treatment for acromegaly with an adjuvant role and possibly of greater value in cases of resistance to other therapeutic options.
 ...
PMID:Pegvisomant: a new treatment modality for acromegaly. 1698 75


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