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Erschienen in: Pituitary 1/2017

08.09.2016

Pegvisomant: a growth hormone receptor antagonist used in the treatment of acromegaly

verfasst von: Nicholas A. Tritos, Beverly M. K. Biller

Erschienen in: Pituitary | Ausgabe 1/2017

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Abstract

Purpose

To review published data on pegvisomant and its therapeutic role in acromegaly.

Methods

Electronic searches of the published literature were conducted using the keywords: acromegaly, growth hormone (GH) receptor (antagonist), pegvisomant, therapy. Relevant articles (n = 141) were retrieved and considered for inclusion in this manuscript.

Results

Pegvisomant is a genetically engineered, recombinant growth hormone receptor antagonist, which is effective in normalizing serum insulin-like growth factor 1 (IGF-1) levels in the majority of patients with acromegaly and ameliorating symptoms and signs associated with GH excess. Pegvisomant does not have direct antiproliferative effects on the underlying somatotroph pituitary adenoma, which is the etiology of GH excess in the vast majority of patients with acromegaly. Therefore, patients receiving pegvisomant monotherapy require regular pituitary imaging in order to monitor for possible increase in tumor size. Adverse events in patients on pegvisomant therapy include skin rashes, lipohypertrophy at injection sites, and idiosyncratic liver toxicity (generally asymptomatic transaminitis that is reversible upon drug discontinuation), thus necessitating regular patient monitoring.

Conclusions

Pegvisomant is an effective therapeutic agent in patients with acromegaly who are not in remission after undergoing pituitary surgery. It mitigates excess GH action, as demonstrated by IGF-1 normalization, but has no direct effects on pituitary tumors causing acromegaly. Regular surveillance for possible tumor growth and adverse effects (hepatotoxicity, skin manifestations) is warranted.
Literatur
1.
Zurück zum Zitat Katznelson L, Laws ER Jr, Melmed S, Molitch ME, Murad MH, Utz A, Wass JA, Endocrine S (2014) Acromegaly: an endocrine society clinical practice guideline. J Clin Endocrinol Metab 99(11):3933–3951. doi:10.1210/jc.2014-2700 CrossRefPubMed Katznelson L, Laws ER Jr, Melmed S, Molitch ME, Murad MH, Utz A, Wass JA, Endocrine S (2014) Acromegaly: an endocrine society clinical practice guideline. J Clin Endocrinol Metab 99(11):3933–3951. doi:10.​1210/​jc.​2014-2700 CrossRefPubMed
2.
3.
Zurück zum Zitat de Vos AM, Ultsch M, Kossiakoff AA (1992) Human growth hormone and extracellular domain of its receptor: crystal structure of the complex. Science 255(5042):306–312CrossRefPubMed de Vos AM, Ultsch M, Kossiakoff AA (1992) Human growth hormone and extracellular domain of its receptor: crystal structure of the complex. Science 255(5042):306–312CrossRefPubMed
4.
Zurück zum Zitat Fuh G, Cunningham BC, Fukunaga R, Nagata S, Goeddel DV, Wells JA (1992) Rational design of potent antagonists to the human growth hormone receptor. Science 256(5064):1677–1680CrossRefPubMed Fuh G, Cunningham BC, Fukunaga R, Nagata S, Goeddel DV, Wells JA (1992) Rational design of potent antagonists to the human growth hormone receptor. Science 256(5064):1677–1680CrossRefPubMed
5.
Zurück zum Zitat Brown RJ, Adams JJ, Pelekanos RA, Wan Y, McKinstry WJ, Palethorpe K, Seeber RM, Monks TA, Eidne KA, Parker MW, Waters MJ (2005) Model for growth hormone receptor activation based on subunit rotation within a receptor dimer. Nat Struct Mol Biol 12(9):814–821. doi:10.1038/nsmb977 CrossRefPubMed Brown RJ, Adams JJ, Pelekanos RA, Wan Y, McKinstry WJ, Palethorpe K, Seeber RM, Monks TA, Eidne KA, Parker MW, Waters MJ (2005) Model for growth hormone receptor activation based on subunit rotation within a receptor dimer. Nat Struct Mol Biol 12(9):814–821. doi:10.​1038/​nsmb977 CrossRefPubMed
8.
Zurück zum Zitat Wang X, Darus CJ, Xu BC, Kopchick JJ (1996) Identification of growth hormone receptor (GHR) tyrosine residues required for GHR phosphorylation and JAK2 and STAT5 activation. Mol Endocrinol 10(10):1249–1260. doi:10.1210/mend.10.10.9121492 PubMed Wang X, Darus CJ, Xu BC, Kopchick JJ (1996) Identification of growth hormone receptor (GHR) tyrosine residues required for GHR phosphorylation and JAK2 and STAT5 activation. Mol Endocrinol 10(10):1249–1260. doi:10.​1210/​mend.​10.​10.​9121492 PubMed
9.
Zurück zum Zitat Wang X, Xu B, Souza SC, Kopchick JJ (1994) Growth hormone (GH) induces tyrosine-phosphorylated proteins in mouse L cells that express recombinant GH receptors. Proc Natl Acad Sci U S A 91(4):1391–1395CrossRefPubMedPubMedCentral Wang X, Xu B, Souza SC, Kopchick JJ (1994) Growth hormone (GH) induces tyrosine-phosphorylated proteins in mouse L cells that express recombinant GH receptors. Proc Natl Acad Sci U S A 91(4):1391–1395CrossRefPubMedPubMedCentral
10.
Zurück zum Zitat Chen WY, Wight DC, Wagner TE, Kopchick JJ (1990) Expression of a mutated bovine growth hormone gene suppresses growth of transgenic mice. Proc Natl Acad Sci U S A 87(13):5061–5065CrossRefPubMedPubMedCentral Chen WY, Wight DC, Wagner TE, Kopchick JJ (1990) Expression of a mutated bovine growth hormone gene suppresses growth of transgenic mice. Proc Natl Acad Sci U S A 87(13):5061–5065CrossRefPubMedPubMedCentral
12.
Zurück zum Zitat Chen WY, Chen NY, Yun J, Wagner TE, Kopchick JJ (1994) In vitro and in vivo studies of antagonistic effects of human growth hormone analogs. J Biol Chem 269(22):15892–15897PubMed Chen WY, Chen NY, Yun J, Wagner TE, Kopchick JJ (1994) In vitro and in vivo studies of antagonistic effects of human growth hormone analogs. J Biol Chem 269(22):15892–15897PubMed
13.
Zurück zum Zitat Ross RJ, Leung KC, Maamra M, Bennett W, Doyle N, Waters MJ, Ho KK (2001) Binding and functional studies with the growth hormone receptor antagonist, B2036-PEG (pegvisomant), reveal effects of pegylation and evidence that it binds to a receptor dimer. J Clin Endocrinol Metab 86(4):1716–1723. doi:10.1210/jcem.86.4.7403 PubMed Ross RJ, Leung KC, Maamra M, Bennett W, Doyle N, Waters MJ, Ho KK (2001) Binding and functional studies with the growth hormone receptor antagonist, B2036-PEG (pegvisomant), reveal effects of pegylation and evidence that it binds to a receptor dimer. J Clin Endocrinol Metab 86(4):1716–1723. doi:10.​1210/​jcem.​86.​4.​7403 PubMed
14.
Zurück zum Zitat Wilson ME (2000) Insulin-like growth factor I (IGF-I) replacement during growth hormone receptor antagonism normalizes serum IGF-binding protein-3 and markers of bone formation in ovariectomized rhesus monkeys. J Clin Endocrinol Metab 85(4):1557–1562. doi:10.1210/jcem.85.4.6522 PubMed Wilson ME (2000) Insulin-like growth factor I (IGF-I) replacement during growth hormone receptor antagonism normalizes serum IGF-binding protein-3 and markers of bone formation in ovariectomized rhesus monkeys. J Clin Endocrinol Metab 85(4):1557–1562. doi:10.​1210/​jcem.​85.​4.​6522 PubMed
15.
Zurück zum Zitat Thorner MO, Strasburger CJ, Wu Z, Straume M, Bidlingmaier M, Pezzoli SS, Zib K, Scarlett JC, Bennett WF (1999) Growth hormone (GH) receptor blockade with a PEG-modified GH (B2036-PEG) lowers serum insulin-like growth factor-I but does not acutely stimulate serum GH. J Clin Endocrinol Metab 84(6):2098–2103. doi:10.1210/jcem.84.6.5732 PubMed Thorner MO, Strasburger CJ, Wu Z, Straume M, Bidlingmaier M, Pezzoli SS, Zib K, Scarlett JC, Bennett WF (1999) Growth hormone (GH) receptor blockade with a PEG-modified GH (B2036-PEG) lowers serum insulin-like growth factor-I but does not acutely stimulate serum GH. J Clin Endocrinol Metab 84(6):2098–2103. doi:10.​1210/​jcem.​84.​6.​5732 PubMed
16.
Zurück zum Zitat Trainer PJ, Drake WM, Katznelson L, Freda PU, Herman-Bonert V, van der Lely AJ, Dimaraki EV, Stewart PM, Friend KE, Vance ML, Besser GM, Scarlett JA, Thorner MO, Parkinson C, Klibanski A, Powell JS, Barkan AL, Sheppard MC, Malsonado M, Rose DR, Clemmons DR, Johannsson G, Bengtsson BA, Stavrou S, Kleinberg DL, Cook DM, Phillips LS, Bidlingmaier M, Strasburger CJ, Hackett S, Zib K, Bennett WF, Davis RJ (2000) Treatment of acromegaly with the growth hormone-receptor antagonist pegvisomant. N Engl J Med 342(16):1171–1177. doi:10.1056/NEJM200004203421604 CrossRefPubMed Trainer PJ, Drake WM, Katznelson L, Freda PU, Herman-Bonert V, van der Lely AJ, Dimaraki EV, Stewart PM, Friend KE, Vance ML, Besser GM, Scarlett JA, Thorner MO, Parkinson C, Klibanski A, Powell JS, Barkan AL, Sheppard MC, Malsonado M, Rose DR, Clemmons DR, Johannsson G, Bengtsson BA, Stavrou S, Kleinberg DL, Cook DM, Phillips LS, Bidlingmaier M, Strasburger CJ, Hackett S, Zib K, Bennett WF, Davis RJ (2000) Treatment of acromegaly with the growth hormone-receptor antagonist pegvisomant. N Engl J Med 342(16):1171–1177. doi:10.​1056/​NEJM200004203421​604 CrossRefPubMed
17.
Zurück zum Zitat van der Lely AJ, Hutson RK, Trainer PJ, Besser GM, Barkan AL, Katznelson L, Klibanski A, Herman-Bonert V, Melmed S, Vance ML, Freda PU, Stewart PM, Friend KE, Clemmons DR, Johannsson G, Stavrou S, Cook DM, Phillips LS, Strasburger CJ, Hackett S, Zib KA, Davis RJ, Scarlett JA, Thorner MO (2001) Long-term treatment of acromegaly with pegvisomant, a growth hormone receptor antagonist. Lancet 358(9295):1754–1759CrossRefPubMed van der Lely AJ, Hutson RK, Trainer PJ, Besser GM, Barkan AL, Katznelson L, Klibanski A, Herman-Bonert V, Melmed S, Vance ML, Freda PU, Stewart PM, Friend KE, Clemmons DR, Johannsson G, Stavrou S, Cook DM, Phillips LS, Strasburger CJ, Hackett S, Zib KA, Davis RJ, Scarlett JA, Thorner MO (2001) Long-term treatment of acromegaly with pegvisomant, a growth hormone receptor antagonist. Lancet 358(9295):1754–1759CrossRefPubMed
18.
Zurück zum Zitat Freda PU, Gordon MB, Kelepouris N, Jonsson P, Koltowska-Haggstrom M, van der Lely AJ (2015) Long-term treatment with pegvisomant as monotherapy in patients with acromegaly: experience from ACROSTUDY. Endocr Pract 21(3):264–274. doi:10.4158/EP14330.OR CrossRefPubMedPubMedCentral Freda PU, Gordon MB, Kelepouris N, Jonsson P, Koltowska-Haggstrom M, van der Lely AJ (2015) Long-term treatment with pegvisomant as monotherapy in patients with acromegaly: experience from ACROSTUDY. Endocr Pract 21(3):264–274. doi:10.​4158/​EP14330.​OR CrossRefPubMedPubMedCentral
19.
Zurück zum Zitat Chanson P, Brue T, Delemer B, Caron P, Borson-Chazot F, Zouater H, Medecins de l’Etude, A (2015) Pegvisomant treatment in patients with acromegaly in clinical practice: The French ACROSTUDY. Ann Endocrinol (Paris) 76(6):664–670. doi:10.1016/j.ando.2015.10.003 CrossRef Chanson P, Brue T, Delemer B, Caron P, Borson-Chazot F, Zouater H, Medecins de l’Etude, A (2015) Pegvisomant treatment in patients with acromegaly in clinical practice: The French ACROSTUDY. Ann Endocrinol (Paris) 76(6):664–670. doi:10.​1016/​j.​ando.​2015.​10.​003 CrossRef
20.
Zurück zum Zitat Bernabeu I, Pico A, Venegas E, Aller J, Alvarez-Escola C, Garcia-Arnes JA, Marazuela M, Jonsson P, Mir N, Vargas MG, Spanish ACROSTUDY group (2016) Safety of long-term treatment with Pegvisomant: analysis of Spanish patients included in global ACROSTUDY. Pituitary 19(2):127–137. doi:10.1007/s11102-015-0691-0 CrossRefPubMed Bernabeu I, Pico A, Venegas E, Aller J, Alvarez-Escola C, Garcia-Arnes JA, Marazuela M, Jonsson P, Mir N, Vargas MG, Spanish ACROSTUDY group (2016) Safety of long-term treatment with Pegvisomant: analysis of Spanish patients included in global ACROSTUDY. Pituitary 19(2):127–137. doi:10.​1007/​s11102-015-0691-0 CrossRefPubMed
21.
Zurück zum Zitat Sievers C, Baur DM, Schwanke A, Buchfelder M, Droste M, Mann K, Stalla GK (2015) Prediction of therapy response in acromegalic patients under pegvisomant therapy within the German ACROSTUDY cohort. Pituitary 18(6):916–923. doi:10.1007/s11102-015-0673-2 CrossRefPubMed Sievers C, Baur DM, Schwanke A, Buchfelder M, Droste M, Mann K, Stalla GK (2015) Prediction of therapy response in acromegalic patients under pegvisomant therapy within the German ACROSTUDY cohort. Pituitary 18(6):916–923. doi:10.​1007/​s11102-015-0673-2 CrossRefPubMed
22.
Zurück zum Zitat Cannavo S, Bogazzi F, Colao A, De Marinis L, Maffei P, Gomez R, Graziano E, Monterubbianesi M, Grottoli S, Italian ACROSTUDY group (2015) Does pegvisomant treatment expertise improve control of resistant acromegaly? The Italian ACROSTUDY experience. J Endocrinol Invest 38(10):1099–1109. doi:10.1007/s40618-015-0289-4 CrossRefPubMed Cannavo S, Bogazzi F, Colao A, De Marinis L, Maffei P, Gomez R, Graziano E, Monterubbianesi M, Grottoli S, Italian ACROSTUDY group (2015) Does pegvisomant treatment expertise improve control of resistant acromegaly? The Italian ACROSTUDY experience. J Endocrinol Invest 38(10):1099–1109. doi:10.​1007/​s40618-015-0289-4 CrossRefPubMed
23.
24.
Zurück zum Zitat Droste M, Domberg J, Buchfelder M, Mann K, Schwanke A, Stalla G, Strasburger CJ (2014) Therapy of acromegalic patients exacerbated by concomitant type 2 diabetes requires higher pegvisomant doses to normalise IGF1 levels. Eur J Endocrinol 171(1):59–68. doi:10.1530/EJE-13-0438 CrossRefPubMed Droste M, Domberg J, Buchfelder M, Mann K, Schwanke A, Stalla G, Strasburger CJ (2014) Therapy of acromegalic patients exacerbated by concomitant type 2 diabetes requires higher pegvisomant doses to normalise IGF1 levels. Eur J Endocrinol 171(1):59–68. doi:10.​1530/​EJE-13-0438 CrossRefPubMed
25.
Zurück zum Zitat Parkinson C, Burman P, Messig M, Trainer PJ (2007) Gender, body weight, disease activity, and previous radiotherapy influence the response to pegvisomant. J Clin Endocrinol Metab 92(1):190–195. doi:10.1210/jc.2006-1412 CrossRefPubMed Parkinson C, Burman P, Messig M, Trainer PJ (2007) Gender, body weight, disease activity, and previous radiotherapy influence the response to pegvisomant. J Clin Endocrinol Metab 92(1):190–195. doi:10.​1210/​jc.​2006-1412 CrossRefPubMed
26.
Zurück zum Zitat Leung KC, Doyle N, Ballesteros M, Waters MJ, Ho KK (2000) Insulin regulation of human hepatic growth hormone receptors: divergent effects on biosynthesis and surface translocation. J Clin Endocrinol Metab 85(12):4712–4720. doi:10.1210/jcem.85.12.7017 PubMed Leung KC, Doyle N, Ballesteros M, Waters MJ, Ho KK (2000) Insulin regulation of human hepatic growth hormone receptors: divergent effects on biosynthesis and surface translocation. J Clin Endocrinol Metab 85(12):4712–4720. doi:10.​1210/​jcem.​85.​12.​7017 PubMed
27.
Zurück zum Zitat Drake WM, Parkinson C, Akker SA, Monson JP, Besser GM, Trainer PJ (2001) Successful treatment of resistant acromegaly with a growth hormone receptor antagonist. Eur J Endocrinol 145(4):451–456CrossRefPubMed Drake WM, Parkinson C, Akker SA, Monson JP, Besser GM, Trainer PJ (2001) Successful treatment of resistant acromegaly with a growth hormone receptor antagonist. Eur J Endocrinol 145(4):451–456CrossRefPubMed
28.
Zurück zum Zitat Herman-Bonert VS, Zib K, Scarlett JA, Melmed S (2000) Growth hormone receptor antagonist therapy in acromegalic patients resistant to somatostatin analogs. J Clin Endocrinol Metab 85(8):2958–2961. doi:10.1210/jcem.85.8.6851 PubMed Herman-Bonert VS, Zib K, Scarlett JA, Melmed S (2000) Growth hormone receptor antagonist therapy in acromegalic patients resistant to somatostatin analogs. J Clin Endocrinol Metab 85(8):2958–2961. doi:10.​1210/​jcem.​85.​8.​6851 PubMed
29.
Zurück zum Zitat Oriola J, Lucas T, Halperin I, Mora M, Perales MJ, Alvarez-Escola C, de Paz MN, Soto GD, Salinas I, Julian MT, Olaizola I, Bernabeu I, Marazuela M, Puig-Domingo M (2013) Germline mutations of AIP gene in somatotropinomas resistant to somatostatin analogues. Eur J Endocrinol 168(1):9–13. doi:10.1530/EJE-12-0457 CrossRefPubMed Oriola J, Lucas T, Halperin I, Mora M, Perales MJ, Alvarez-Escola C, de Paz MN, Soto GD, Salinas I, Julian MT, Olaizola I, Bernabeu I, Marazuela M, Puig-Domingo M (2013) Germline mutations of AIP gene in somatotropinomas resistant to somatostatin analogues. Eur J Endocrinol 168(1):9–13. doi:10.​1530/​EJE-12-0457 CrossRefPubMed
30.
Zurück zum Zitat Galland F, Kamenicky P, Affres H, Reznik Y, Pontvert D, Le Bouc Y, Young J, Chanson P (2006) McCune-Albright syndrome and acromegaly: effects of hypothalamopituitary radiotherapy and/or pegvisomant in somatostatin analog-resistant patients. J Clin Endocrinol Metab 91(12):4957–4961. doi:10.1210/jc.2006-0561 CrossRefPubMed Galland F, Kamenicky P, Affres H, Reznik Y, Pontvert D, Le Bouc Y, Young J, Chanson P (2006) McCune-Albright syndrome and acromegaly: effects of hypothalamopituitary radiotherapy and/or pegvisomant in somatostatin analog-resistant patients. J Clin Endocrinol Metab 91(12):4957–4961. doi:10.​1210/​jc.​2006-0561 CrossRefPubMed
31.
Zurück zum Zitat Beckers A, Lodish MB, Trivellin G, Rostomyan L, Lee M, Faucz FR, Yuan B, Choong CS, Caberg JH, Verrua E, Naves LA, Cheetham TD, Young J, Lysy PA, Petrossians P, Cotterill A, Shah NS, Metzger D, Castermans E, Ambrosio MR, Villa C, Strebkova N, Mazerkina N, Gaillard S, Barra GB, Casulari LA, Neggers SJ, Salvatori R, Jaffrain-Rea ML, Zacharin M, Santamaria BL, Zacharieva S, Lim EM, Mantovani G, Zatelli MC, Collins MT, Bonneville JF, Quezado M, Chittiboina P, Oldfield EH, Bours V, Liu P, WdH W, Pellegata N, Lupski JR, Daly AF, Stratakis CA (2015) X-linked acrogigantism syndrome: clinical profile and therapeutic responses. Endocr Relat Cancer 22(3):353–367. doi:10.1530/ERC-15-0038 CrossRefPubMedPubMedCentral Beckers A, Lodish MB, Trivellin G, Rostomyan L, Lee M, Faucz FR, Yuan B, Choong CS, Caberg JH, Verrua E, Naves LA, Cheetham TD, Young J, Lysy PA, Petrossians P, Cotterill A, Shah NS, Metzger D, Castermans E, Ambrosio MR, Villa C, Strebkova N, Mazerkina N, Gaillard S, Barra GB, Casulari LA, Neggers SJ, Salvatori R, Jaffrain-Rea ML, Zacharin M, Santamaria BL, Zacharieva S, Lim EM, Mantovani G, Zatelli MC, Collins MT, Bonneville JF, Quezado M, Chittiboina P, Oldfield EH, Bours V, Liu P, WdH W, Pellegata N, Lupski JR, Daly AF, Stratakis CA (2015) X-linked acrogigantism syndrome: clinical profile and therapeutic responses. Endocr Relat Cancer 22(3):353–367. doi:10.​1530/​ERC-15-0038 CrossRefPubMedPubMedCentral
34.
35.
Zurück zum Zitat Higham CE, Thomas JD, Bidlingmaier M, Drake WM, Trainer PJ (2009) Successful use of weekly pegvisomant administration in patients with acromegaly. Eur J Endocrinol 161(1):21–25. doi:10.1530/EJE-08-0990 CrossRefPubMed Higham CE, Thomas JD, Bidlingmaier M, Drake WM, Trainer PJ (2009) Successful use of weekly pegvisomant administration in patients with acromegaly. Eur J Endocrinol 161(1):21–25. doi:10.​1530/​EJE-08-0990 CrossRefPubMed
36.
Zurück zum Zitat Jehle S, Reyes CM, Sundeen RE, Freda PU (2005) Alternate-day administration of pegvisomant maintains normal serum insulin-like growth factor-I levels in patients with acromegaly. J Clin Endocrinol Metab 90(3):1588–1593. doi:10.1210/jc.2004-1967 CrossRefPubMed Jehle S, Reyes CM, Sundeen RE, Freda PU (2005) Alternate-day administration of pegvisomant maintains normal serum insulin-like growth factor-I levels in patients with acromegaly. J Clin Endocrinol Metab 90(3):1588–1593. doi:10.​1210/​jc.​2004-1967 CrossRefPubMed
37.
Zurück zum Zitat Van der Lely AJ, Jonsson PJ, Wilton P, Akerblad AC, Cara J, Ghigo E (2016) Treatment with high doses of pegvisomant in 56 patients with acromegaly: experience from ACROSTUDY. Eur J Endocrinol. doi:10.1530/EJE-16-0008 Van der Lely AJ, Jonsson PJ, Wilton P, Akerblad AC, Cara J, Ghigo E (2016) Treatment with high doses of pegvisomant in 56 patients with acromegaly: experience from ACROSTUDY. Eur J Endocrinol. doi:10.​1530/​EJE-16-0008
38.
39.
Zurück zum Zitat Barkan AL, Burman P, Clemmons DR, Drake WM, Gagel RF, Harris PE, Trainer PJ, van der Lely AJ, Vance ML (2005) Glucose homeostasis and safety in patients with acromegaly converted from long-acting octreotide to pegvisomant. J Clin Endocrinol Metab 90(10):5684–5691. doi:10.1210/jc.2005-0331 CrossRefPubMed Barkan AL, Burman P, Clemmons DR, Drake WM, Gagel RF, Harris PE, Trainer PJ, van der Lely AJ, Vance ML (2005) Glucose homeostasis and safety in patients with acromegaly converted from long-acting octreotide to pegvisomant. J Clin Endocrinol Metab 90(10):5684–5691. doi:10.​1210/​jc.​2005-0331 CrossRefPubMed
40.
Zurück zum Zitat Parkinson C, Kassem M, Heickendorff L, Flyvbjerg A, Trainer PJ (2003) Pegvisomant-induced serum insulin-like growth factor-I normalization in patients with acromegaly returns elevated markers of bone turnover to normal. J Clin Endocrinol Metab 88(12):5650–5655. doi:10.1210/jc.2003-030772 CrossRefPubMed Parkinson C, Kassem M, Heickendorff L, Flyvbjerg A, Trainer PJ (2003) Pegvisomant-induced serum insulin-like growth factor-I normalization in patients with acromegaly returns elevated markers of bone turnover to normal. J Clin Endocrinol Metab 88(12):5650–5655. doi:10.​1210/​jc.​2003-030772 CrossRefPubMed
41.
Zurück zum Zitat Trainer PJ, Drake WM, Perry LA, Taylor NF, Besser GM, Monson JP (2001) Modulation of cortisol metabolism by the growth hormone receptor antagonist pegvisomant in patients with acromegaly. J Clin Endocrinol Metab 86(7):2989–2992. doi:10.1210/jcem.86.7.7664 PubMed Trainer PJ, Drake WM, Perry LA, Taylor NF, Besser GM, Monson JP (2001) Modulation of cortisol metabolism by the growth hormone receptor antagonist pegvisomant in patients with acromegaly. J Clin Endocrinol Metab 86(7):2989–2992. doi:10.​1210/​jcem.​86.​7.​7664 PubMed
42.
Zurück zum Zitat Higham CE, Atkinson AB, Aylwin S, Bidlingmaier M, Drake WM, Lewis A, Martin NM, Moyes V, Newell-Price J, Trainer PJ (2012) Effective combination treatment with cabergoline and low-dose pegvisomant in active acromegaly: a prospective clinical trial. J Clin Endocrinol Metab 97(4):1187–1193. doi:10.1210/jc.2011-2603 CrossRefPubMed Higham CE, Atkinson AB, Aylwin S, Bidlingmaier M, Drake WM, Lewis A, Martin NM, Moyes V, Newell-Price J, Trainer PJ (2012) Effective combination treatment with cabergoline and low-dose pegvisomant in active acromegaly: a prospective clinical trial. J Clin Endocrinol Metab 97(4):1187–1193. doi:10.​1210/​jc.​2011-2603 CrossRefPubMed
43.
Zurück zum Zitat Neggers SJ, Franck SE, de Rooij FW, Dallenga AH, Poublon RM, Feelders RA, Janssen JA, Buchfelder M, Hofland LJ, Jorgensen JO, van der Lely AJ (2014) Long-term efficacy and safety of pegvisomant in combination with long-acting somatostatin analogs in acromegaly. J Clin Endocrinol Metab 99(10):3644–3652. doi:10.1210/jc.2014-2032 CrossRefPubMed Neggers SJ, Franck SE, de Rooij FW, Dallenga AH, Poublon RM, Feelders RA, Janssen JA, Buchfelder M, Hofland LJ, Jorgensen JO, van der Lely AJ (2014) Long-term efficacy and safety of pegvisomant in combination with long-acting somatostatin analogs in acromegaly. J Clin Endocrinol Metab 99(10):3644–3652. doi:10.​1210/​jc.​2014-2032 CrossRefPubMed
44.
Zurück zum Zitat van der Lely AJ, Biller BM, Brue T, Buchfelder M, Ghigo E, Gomez R, Hey-Hadavi J, Lundgren F, Rajicic N, Strasburger CJ, Webb SM, Koltowska-Haggstrom M (2012) Long-term safety of pegvisomant in patients with acromegaly: comprehensive review of 1288 subjects in ACROSTUDY. J Clin Endocrinol Metab 97(5):1589–1597. doi:10.1210/jc.2011-2508 CrossRefPubMed van der Lely AJ, Biller BM, Brue T, Buchfelder M, Ghigo E, Gomez R, Hey-Hadavi J, Lundgren F, Rajicic N, Strasburger CJ, Webb SM, Koltowska-Haggstrom M (2012) Long-term safety of pegvisomant in patients with acromegaly: comprehensive review of 1288 subjects in ACROSTUDY. J Clin Endocrinol Metab 97(5):1589–1597. doi:10.​1210/​jc.​2011-2508 CrossRefPubMed
45.
Zurück zum Zitat Feenstra J, van Aken MO, de Herder WW, Feelders RA, van der Lely AJ (2006) Drug-induced hepatitis in an acromegalic patient during combined treatment with pegvisomant and octreotide long-acting repeatable attributed to the use of pegvisomant. Eur J Endocrinol 154(6):805–806. doi:10.1530/eje.1.02160 CrossRefPubMed Feenstra J, van Aken MO, de Herder WW, Feelders RA, van der Lely AJ (2006) Drug-induced hepatitis in an acromegalic patient during combined treatment with pegvisomant and octreotide long-acting repeatable attributed to the use of pegvisomant. Eur J Endocrinol 154(6):805–806. doi:10.​1530/​eje.​1.​02160 CrossRefPubMed
46.
Zurück zum Zitat Biering H, Saller B, Bauditz J, Pirlich M, Rudolph B, Johne A, Buchfelder M, Mann K, Droste M, Schreiber I, Lochs H, Strasburger CJ, German pegvisomant investigators (2006) Elevated transaminases during medical treatment of acromegaly: a review of the German pegvisomant surveillance experience and a report of a patient with histologically proven chronic mild active hepatitis. Eur J Endocrinol 154(2):213–220. doi:10.1530/eje.1.02079 CrossRefPubMed Biering H, Saller B, Bauditz J, Pirlich M, Rudolph B, Johne A, Buchfelder M, Mann K, Droste M, Schreiber I, Lochs H, Strasburger CJ, German pegvisomant investigators (2006) Elevated transaminases during medical treatment of acromegaly: a review of the German pegvisomant surveillance experience and a report of a patient with histologically proven chronic mild active hepatitis. Eur J Endocrinol 154(2):213–220. doi:10.​1530/​eje.​1.​02079 CrossRefPubMed
47.
Zurück zum Zitat Brian SR, Bidlingmaier M, Wajnrajch MP, Weinzimer SA, Inzucchi SE (2007) Treatment of acromegaly with pegvisomant during pregnancy: maternal and fetal effects. J Clin Endocrinol Metab 92(9):3374–3377. doi:10.1210/jc.2007-0997 CrossRefPubMed Brian SR, Bidlingmaier M, Wajnrajch MP, Weinzimer SA, Inzucchi SE (2007) Treatment of acromegaly with pegvisomant during pregnancy: maternal and fetal effects. J Clin Endocrinol Metab 92(9):3374–3377. doi:10.​1210/​jc.​2007-0997 CrossRefPubMed
48.
49.
Zurück zum Zitat Smith LE, Kopchick JJ, Chen W, Knapp J, Kinose F, Daley D, Foley E, Smith RG, Schaeffer JM (1997) Essential role of growth hormone in ischemia-induced retinal neovascularization. Science 276(5319):1706–1709CrossRefPubMed Smith LE, Kopchick JJ, Chen W, Knapp J, Kinose F, Daley D, Foley E, Smith RG, Schaeffer JM (1997) Essential role of growth hormone in ischemia-induced retinal neovascularization. Science 276(5319):1706–1709CrossRefPubMed
50.
Zurück zum Zitat Flyvbjerg A, Bennett WF, Rasch R, Kopchick JJ, Scarlett JA (1999) Inhibitory effect of a growth hormone receptor antagonist (G120 K-PEG) on renal enlargement, glomerular hypertrophy, and urinary albumin excretion in experimental diabetes in mice. Diabetes 48(2):377–382CrossRefPubMed Flyvbjerg A, Bennett WF, Rasch R, Kopchick JJ, Scarlett JA (1999) Inhibitory effect of a growth hormone receptor antagonist (G120 K-PEG) on renal enlargement, glomerular hypertrophy, and urinary albumin excretion in experimental diabetes in mice. Diabetes 48(2):377–382CrossRefPubMed
51.
Zurück zum Zitat Dagnaes-Hansen F, Duan H, Rasmussen LM, Friend KE, Flyvbjerg A (2004) Growth hormone receptor antagonist administration inhibits growth of human colorectal carcinoma in nude mice. Anticancer Res 24(6):3735–3742PubMed Dagnaes-Hansen F, Duan H, Rasmussen LM, Friend KE, Flyvbjerg A (2004) Growth hormone receptor antagonist administration inhibits growth of human colorectal carcinoma in nude mice. Anticancer Res 24(6):3735–3742PubMed
52.
Zurück zum Zitat Friend KE, Khandwala HM, Flyvbjerg A, Hill H, Li J, McCutcheon IE (2001) Growth hormone and insulin-like growth factor-I: effects on the growth of glioma cell lines. Growth Horm IGF Res 11(2):84–91. doi:10.1054/ghir.2000.0183 CrossRefPubMed Friend KE, Khandwala HM, Flyvbjerg A, Hill H, Li J, McCutcheon IE (2001) Growth hormone and insulin-like growth factor-I: effects on the growth of glioma cell lines. Growth Horm IGF Res 11(2):84–91. doi:10.​1054/​ghir.​2000.​0183 CrossRefPubMed
54.
55.
Zurück zum Zitat Yin D, Vreeland F, Schaaf LJ, Millham R, Duncan BA, Sharma A (2007) Clinical pharmacodynamic effects of the growth hormone receptor antagonist pegvisomant: implications for cancer therapy. Clin Cancer Res 13(3):1000–1009. doi:10.1158/1078-0432.CCR-06-1910 CrossRefPubMed Yin D, Vreeland F, Schaaf LJ, Millham R, Duncan BA, Sharma A (2007) Clinical pharmacodynamic effects of the growth hormone receptor antagonist pegvisomant: implications for cancer therapy. Clin Cancer Res 13(3):1000–1009. doi:10.​1158/​1078-0432.​CCR-06-1910 CrossRefPubMed
57.
Zurück zum Zitat Drake WM, Grossman AB, Hutson RK (2005) Effect of treatment with pegvisomant on meningioma growth in vivo. Eur J Endocrinol 152(1):161–162CrossRefPubMed Drake WM, Grossman AB, Hutson RK (2005) Effect of treatment with pegvisomant on meningioma growth in vivo. Eur J Endocrinol 152(1):161–162CrossRefPubMed
Metadaten
Titel
Pegvisomant: a growth hormone receptor antagonist used in the treatment of acromegaly
verfasst von
Nicholas A. Tritos
Beverly M. K. Biller
Publikationsdatum
08.09.2016
Verlag
Springer US
Erschienen in
Pituitary / Ausgabe 1/2017
Print ISSN: 1386-341X
Elektronische ISSN: 1573-7403
DOI
https://doi.org/10.1007/s11102-016-0753-y

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