Treatment of Acromegaly with the Growth Hormone–Receptor Antagonist Pegvisomant
Acromegaly is a chronic debilitating disorder resulting from excessive secretion of growth hormone and a resulting increase in the production of insulin-like growth factor I (IGF-I). It is usually caused by somatotroph adenomas of the pituitary gland. The goal of treatment is to reverse the effects...
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| Published in | The New England journal of medicine Vol. 342; no. 16; pp. 1171 - 1177 |
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| Main Authors | , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , |
| Format | Journal Article |
| Language | English |
| Published |
Boston, MA
Massachusetts Medical Society
20.04.2000
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| Subjects | |
| Online Access | Get full text |
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| Abstract | Acromegaly is a chronic debilitating disorder resulting from excessive secretion of growth hormone and a resulting increase in the production of insulin-like growth factor I (IGF-I). It is usually caused by somatotroph adenomas of the pituitary gland. The goal of treatment is to reverse the effects of the hypersecretion of growth hormone and normalize production of IGF-I. Effective treatment ameliorates the symptoms and signs of the disease and lowers the mortality rate.
The current treatments for acromegaly are surgical removal of the adenoma, radiation therapy, and drug treatment. Among patients treated surgically, only 60 percent of patients overall and less . . . |
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| AbstractList | Patients with acromegaly are currently treated with surgery, radiation therapy, and drugs to reduce hypersecretion of growth hormone, but the treatments may be ineffective and have adverse effects. Pegvisomant is a genetically engineered growth hormone-receptor antagonist that blocks the action of growth hormone.We conducted a 12-week, randomized, double-blind study of three daily doses of pegvisomant (10 mg, 15 mg, and 20 mg) and placebo, given subcutaneously, in 112 patients with acromegaly.The mean (+/-SD) serum concentration of insulin-like growth factor I (IGF-I) decreased from base line by 4.0+/-16.8 percent in the placebo group, 26.7+/-27.9 percent in the group that received 10 mg of pegvisomant per day, 50.1+/-26.7 percent in the group that received 15 mg of pegvisomant per day, and 62.5+/-21.3 percent in the group that received 20 mg of pegvisomant per day (P<0.001 for the comparison of each pegvisomant group with placebo), and the concentrations became normal in 10 percent, 54 percent, 81 percent, and 89 percent of patients, respectively (P<0.001 for each comparison with placebo). Among patients treated with 15 mg or 20 mg of pegvisomant per day, there were significant decreases in ring size, soft-tissue swelling, the degree of excessive perspiration, and fatigue. The score fortotal symptoms and signs of acromegaly decreased significantly in all groups receiving pegvisomant (P< or =0.05). The incidence of adverse effects was similar in all groups.On the basis of these preliminary results, treatment of patients who have acromegaly with a growth hormone-receptor antagonist results in a reduction in serum IGF-I concentrations and in clinical improvement. Patients with acromegaly are currently treated with surgery, radiation therapy, and drugs to reduce hypersecretion of growth hormone, but the treatments may be ineffective and have adverse effects. Pegvisomant is a genetically engineered growth hormone-receptor antagonist that blocks the action of growth hormone. We conducted a 12-week, randomized, double-blind study of three daily doses of pegvisomant (10 mg, 15 mg, and 20 mg) and placebo, given subcutaneously, in 112 patients with acromegaly. The mean (+/-SD) serum concentration of insulin-like growth factor I (IGF-I) decreased from base line by 4.0+/-16.8 percent in the placebo group, 26.7+/-27.9 percent in the group that received 10 mg of pegvisomant per day, 50.1+/-26.7 percent in the group that received 15 mg of pegvisomant per day, and 62.5+/-21.3 percent in the group that received 20 mg of pegvisomant per day (P<0.001 for the comparison of each pegvisomant group with placebo), and the concentrations became normal in 10 percent, 54 percent, 81 percent, and 89 percent of patients, respectively (P<0.001 for each comparison with placebo). Among patients treated with 15 mg or 20 mg of pegvisomant per day, there were significant decreases in ring size, soft-tissue swelling, the degree of excessive perspiration, and fatigue. The score fortotal symptoms and signs of acromegaly decreased significantly in all groups receiving pegvisomant (P< or =0.05). The incidence of adverse effects was similar in all groups. On the basis of these preliminary results, treatment of patients who have acromegaly with a growth hormone-receptor antagonist results in a reduction in serum IGF-I concentrations and in clinical improvement. Acromegaly is a chronic debilitating disorder resulting from excessive secretion of growth hormone and a resulting increase in the production of insulin-like growth factor I (IGF-I). It is usually caused by somatotroph adenomas of the pituitary gland. The goal of treatment is to reverse the effects of the hypersecretion of growth hormone and normalize production of IGF-I. Effective treatment ameliorates the symptoms and signs of the disease and lowers the mortality rate. The current treatments for acromegaly are surgical removal of the adenoma, radiation therapy, and drug treatment. Among patients treated surgically, only 60 percent of patients overall and less . . . BACKGROUNDPatients with acromegaly are currently treated with surgery, radiation therapy, and drugs to reduce hypersecretion of growth hormone, but the treatments may be ineffective and have adverse effects. Pegvisomant is a genetically engineered growth hormone-receptor antagonist that blocks the action of growth hormone.METHODSWe conducted a 12-week, randomized, double-blind study of three daily doses of pegvisomant (10 mg, 15 mg, and 20 mg) and placebo, given subcutaneously, in 112 patients with acromegaly.RESULTSThe mean (+/-SD) serum concentration of insulin-like growth factor I (IGF-I) decreased from base line by 4.0+/-16.8 percent in the placebo group, 26.7+/-27.9 percent in the group that received 10 mg of pegvisomant per day, 50.1+/-26.7 percent in the group that received 15 mg of pegvisomant per day, and 62.5+/-21.3 percent in the group that received 20 mg of pegvisomant per day (P<0.001 for the comparison of each pegvisomant group with placebo), and the concentrations became normal in 10 percent, 54 percent, 81 percent, and 89 percent of patients, respectively (P<0.001 for each comparison with placebo). Among patients treated with 15 mg or 20 mg of pegvisomant per day, there were significant decreases in ring size, soft-tissue swelling, the degree of excessive perspiration, and fatigue. The score fortotal symptoms and signs of acromegaly decreased significantly in all groups receiving pegvisomant (P< or =0.05). The incidence of adverse effects was similar in all groups.CONCLUSIONSOn the basis of these preliminary results, treatment of patients who have acromegaly with a growth hormone-receptor antagonist results in a reduction in serum IGF-I concentrations and in clinical improvement. Trainer et al studied various treatments of acromegaly, particularly treatment with the growth hormone-receptor antagonist pegvisomant. Treatment of patients with acromegaly with a growth hormone-receptor antagonist results in a reduction in serum IGF-I concentrations and in clinical improvement. |
| Author | Bidlingmaier, Martin Besser, G. Michael Sheppard, Michael C Stavrou, Stavros Bennett, William F Phillips, Lawrence S Strasburger, Christian J Trainer, Peter J Stewart, Paul M Zib, Kenneth Scarlett, John A Davis, Robert J Cook, David M Katznelson, Laurence Maldonado, Mario Thorner, Michael O Rose, D. Roderick Clemmons, David R Kleinberg, David L Parkinson, Craig Herman-Bonert, Vivien Friend, Keith E van der Lely, A.J Klibanski, Anne Hackett, Suzanne Barkan, Ariel L Freda, Pamela U Johannsson, Gudmundur Dimaraki, Eleni V Powell, Jeffrey S Drake, William M Vance, Mary Lee Bengt-Åke Bengtsson, Bengt-Åke |
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| BackLink | http://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=1331441$$DView record in Pascal Francis https://www.ncbi.nlm.nih.gov/pubmed/10770982$$D View this record in MEDLINE/PubMed https://gup.ub.gu.se/publication/251174$$DView record from Swedish Publication Index |
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| References | 10770989 - N Engl J Med. 2000 Apr 20;342(16):1210-1 r020 r021 r022 r001 r023 Barkan AL (r007) 1989; 18 r017 r018 r019 r013 r014 r015 r016 r010 r012 r006 r008 r009 r002 Ezzat S (r011) 1995; 18 r024 r003 r025 r004 r026 r005 |
| References_xml | – ident: r013 doi: 10.1210/jc.82.1.23 – volume: 18 start-page: 364 year: 1995 ident: r011 publication-title: J Endocrinol Invest doi: 10.1007/BF03347839 contributor: fullname: Ezzat S – ident: r026 doi: 10.1016/S0026-0495(96)90087-6 – volume: 18 start-page: 277 year: 1989 ident: r007 publication-title: Endocrinol Metab Clin North Am doi: 10.1016/S0889-8529(18)30372-4 contributor: fullname: Barkan AL – ident: r022 – ident: r008 doi: 10.1530/eje.0.1390516 – ident: r025 doi: 10.1210/jc.82.1.18 – ident: r005 doi: 10.1210/jc.82.10.3187 – ident: r017 doi: 10.1126/science.256.5064.1677 – ident: r012 doi: 10.1210/jc.80.9.2768 – ident: r002 doi: 10.1046/j.1365-2265.1996.8370847.x – ident: r024 doi: 10.1210/en.140.8.3853 – ident: r015 doi: 10.1056/NEJM199601253340408 – ident: r021 doi: 10.1074/jbc.271.36.21969 – ident: r003 doi: 10.3171/jns.1998.89.3.0353 – ident: r016 doi: 10.1073/pnas.87.13.5061 – ident: r006 doi: 10.1210/jc.82.10.3185 – ident: r020 doi: 10.1021/bk-1997-0680.ch012 – ident: r019 doi: 10.1126/science.1948064 – ident: r009 doi: 10.1210/jc.83.2.374 – ident: r023 – ident: r018 doi: 10.1097/00004728-199207000-00004 – ident: r010 doi: 10.1001/archinte.151.8.1573 – ident: r001 doi: 10.1210/jc.83.10.3419 – ident: r004 doi: 10.1046/j.1365-2265.1999.00760.x – ident: r014 doi: 10.1023/A:1009980404404 |
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| Snippet | Acromegaly is a chronic debilitating disorder resulting from excessive secretion of growth hormone and a resulting increase in the production of insulin-like... Patients with acromegaly are currently treated with surgery, radiation therapy, and drugs to reduce hypersecretion of growth hormone, but the treatments may be... Trainer et al studied various treatments of acromegaly, particularly treatment with the growth hormone-receptor antagonist pegvisomant. Treatment of patients... BACKGROUNDPatients with acromegaly are currently treated with surgery, radiation therapy, and drugs to reduce hypersecretion of growth hormone, but the... |
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| SubjectTerms | Acromegaly Acromegaly - blood Acromegaly - drug therapy Adenoma Adenoma - drug therapy Adenoma - pathology Adult adverse effects analogs & derivatives antagonists & inhibitors Autoantibodies Autoantibodies - blood Biological and medical sciences blood Double-Blind Method drug therapy Endocrinology and Diabetes Endokrinologi och diabetes Female Growth hormones Hormones. Endocrine system Hospitals Human Growth Hormone Human Growth Hormone - adverse effects Human Growth Hormone - analogs & derivatives Human Growth Hormone - blood Human Growth Hormone - immunology Human Growth Hormone - therapeutic use Humans immunology Insulin-Like Growth Factor I Insulin-Like Growth Factor I - metabolism Male Medical sciences metabolism Middle Aged Mortality pathology Pharmacology. Drug treatments Pituitary gland Pituitary Neoplasms Pituitary Neoplasms - drug therapy Pituitary Neoplasms - pathology Receptors Receptors, Somatotropin - antagonists & inhibitors Somatotropin therapeutic use |
| Title | Treatment of Acromegaly with the Growth Hormone–Receptor Antagonist Pegvisomant |
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