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    The place of pegvisomant in the management of acromegaly.

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    Authors
    Parkinson, Craig
    Trainer, Peter J
    Affiliation
    Department of Endocrinology, Christie Hospital, Wilmslow Road, Manchester, M20 4BX, UK.
    Issue Date
    2001-09
    
    Metadata
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    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.
    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
    URI
    http://hdl.handle.net/10541/78980
    DOI
    10.1517/13543784.10.9.1725
    PubMed ID
    11772281
    Type
    Article
    Language
    en
    ISSN
    1354-3784
    ae974a485f413a2113503eed53cd6c53
    10.1517/13543784.10.9.1725
    Scopus Count
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