The place of pegvisomant in the management of acromegaly

Conventional treatments for acromegaly include surgery, radiotherapy, dopam ine 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 signifi cant number of patients with sub-optimal serum GH and insulin-like growth f actor-I (IGF-I) levels, which have been linked to increased morbidity and m ortality. The GH receptor antagonist pegvisomant is a genetically engineere d analogue of GH that prevents functional dimerisation of the growth hormon e receptor (GHR); a process that is critical to GH action at the cellular l evel. A crucial amino acid substitution at gly(120) to arg(120) within the 3rd alpha helix of the antagonist prevents functional GHR dimerisation. Peg visomant represents a novel treatment for acromegaly as, unlike existing tr eatment modalities, the effectiveness of pegvisomant is independent of pitu itary tumour characteristics. Initial clinical studies in patients with act ive acromegaly have demonstrated serum IGF-I normalisation in over 90% of p atients receiving 20 mg per day, such that, in terms of serum IGF-I normali sation, pegvisomant now represents the most effective medical treatment for acromegaly. Although there are limited long-term data on the use of pegvis omant and questions regarding pituitary tumour growth and altered liver fun ction remain, this therapy offers the prospect of serum IGF-I normalisation in the vast majority of patients with active acromegaly.