2.50
Hdl Handle:
http://hdl.handle.net/10541/78980
Title:
The place of pegvisomant in the management of acromegaly.
Authors:
Parkinson, Craig; Trainer, Peter J
Abstract:
Conventional treatments for acromegaly include surgery, radiotherapy, dopamine agonists and somatostatin (SMS) analogues, which effect disease control by lowering circulating growth hormone (GH). Due to variability in tumour characteristics, combinations of these treatment modalities leave a significant number of patients with sub-optimal serum GH and insulin-like growth factor-I (IGF-I) levels, which have been linked to increased morbidity and mortality. The GH receptor antagonist pegvisomant is a genetically engineered analogue of GH that prevents functional dimerisation of the growth hormone receptor (GHR); a process that is critical to GH action at the cellular level. A crucial amino acid substitution at Gly(120) to Arg(120) within the third alpha helix of the antagonist prevents functional GHR dimerisation. Pegvisomant represents a novel treatment for acromegaly as, unlike existing treatment modalities, the effectiveness of pegvisomant is independent of pituitary tumour characteristics. Initial clinical studies in patients with active acromegaly have demonstrated serum IGF-I normalisation in over 90% of patients receiving 20 mg per day, such that, in terms of serum IGF-I normalisation, pegvisomant now represents the most effective medical treatment for acromegaly. Although there are limited long-term data on the use of pegvisomant and questions regarding pituitary tumour growth and altered liver function remain, this therapy offers the prospect of serum IGF-I normalisation in the vast majority of patients with active acromegaly.
Affiliation:
Department of Endocrinology, Christie Hospital, Wilmslow Road, Manchester, M20 4BX, UK.
Citation:
The place of pegvisomant in the management of acromegaly. 2001, 10 (9):1725-35 Expert Opin Investig Drugs
Journal:
Expert Opinion on Investigational Drugs
Issue Date:
Sep-2001
URI:
http://hdl.handle.net/10541/78980
DOI:
10.1517/13543784.10.9.1725
PubMed ID:
11772281
Type:
Article
Language:
en
ISSN:
1354-3784
Appears in Collections:
All Christie Publications

Full metadata record

DC FieldValue Language
dc.contributor.authorParkinson, Craig-
dc.contributor.authorTrainer, Peter J-
dc.date.accessioned2009-08-27T15:49:18Z-
dc.date.available2009-08-27T15:49:18Z-
dc.date.issued2001-09-
dc.identifier.citationThe place of pegvisomant in the management of acromegaly. 2001, 10 (9):1725-35 Expert Opin Investig Drugsen
dc.identifier.issn1354-3784-
dc.identifier.pmid11772281-
dc.identifier.doi10.1517/13543784.10.9.1725-
dc.identifier.urihttp://hdl.handle.net/10541/78980-
dc.description.abstractConventional treatments for acromegaly include surgery, radiotherapy, dopamine agonists and somatostatin (SMS) analogues, which effect disease control by lowering circulating growth hormone (GH). Due to variability in tumour characteristics, combinations of these treatment modalities leave a significant number of patients with sub-optimal serum GH and insulin-like growth factor-I (IGF-I) levels, which have been linked to increased morbidity and mortality. The GH receptor antagonist pegvisomant is a genetically engineered analogue of GH that prevents functional dimerisation of the growth hormone receptor (GHR); a process that is critical to GH action at the cellular level. A crucial amino acid substitution at Gly(120) to Arg(120) within the third alpha helix of the antagonist prevents functional GHR dimerisation. Pegvisomant represents a novel treatment for acromegaly as, unlike existing treatment modalities, the effectiveness of pegvisomant is independent of pituitary tumour characteristics. Initial clinical studies in patients with active acromegaly have demonstrated serum IGF-I normalisation in over 90% of patients receiving 20 mg per day, such that, in terms of serum IGF-I normalisation, pegvisomant now represents the most effective medical treatment for acromegaly. Although there are limited long-term data on the use of pegvisomant and questions regarding pituitary tumour growth and altered liver function remain, this therapy offers the prospect of serum IGF-I normalisation in the vast majority of patients with active acromegaly.en
dc.language.isoenen
dc.subjectPituitary Canceren
dc.subject.meshAcromegaly-
dc.subject.meshAnimals-
dc.subject.meshCell Division-
dc.subject.meshClinical Trials, Phase I as Topic-
dc.subject.meshClinical Trials, Phase II as Topic-
dc.subject.meshClinical Trials, Phase III as Topic-
dc.subject.meshHuman Growth Hormone-
dc.subject.meshHumans-
dc.subject.meshPituitary Neoplasms-
dc.subject.meshRandomized Controlled Trials as Topic-
dc.subject.meshReceptors, Somatotropin-
dc.titleThe place of pegvisomant in the management of acromegaly.en
dc.typeArticleen
dc.contributor.departmentDepartment of Endocrinology, Christie Hospital, Wilmslow Road, Manchester, M20 4BX, UK.en
dc.identifier.journalExpert Opinion on Investigational Drugsen

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