Pegvisomant: Clinical use in patients with acromegaly
PDF (Español (España))
xhtml (Español (España))

Keywords

Pegvisomant
acromegaly
GH antagonist
IGF-1
lanreotide
octreotide
pasireotide

How to Cite

Román-González, A., Padilla-Zambrano, H., Builes-Barrera, C. A., & Tovar, H. (2022). Pegvisomant: Clinical use in patients with acromegaly. Revista Colombiana De Endocrinología, Diabetes &Amp; Metabolismo, 9(3). https://doi.org/10.53853/encr.9.3.763

Abstract

Background: Currently, the management of patients with acromegaly includes surgery, radiation therapy, and drug therapy. Although surgery is the first-line treatment, a large percentage of patients will require additional management with radiotherapy and pharmacotherapy.

Purpose: To review the pharmacology and clinical studies of pegvisomant.

Methodology: Electronic databases such as Medline and PubMed were searched with the term pegvisomant. Clinical studies and relevant data regarding pegvisomant in the management of acromegaly are presented.

Results: Somatostatin analogs are the cornerstone of drug therapy for this entity; however, recent studies have reported low rates of disease control. To achieve better control, Pegvisomant has been introduced. This drug is a growth hormone analog that binds to the receptor but does not induce conformational changes for signal transduction. Therefore, it does not inhibit growth hormone secretion but rather its physiological effects on target tissues. To date, it has shown efficacy in normalizing serum IGF-1 levels both in monotherapy and in combination therapy.

Conclusions: Absence of acromegaly control despite first line treatment should trigger consideration of second line treatment like pegvisomant or pasireotide. Individual characteristics allow the clinician to choose the better option to the patient. Pegvisomant is an effective drug to control this disease.

https://doi.org/10.53853/encr.9.3.763
PDF (Español (España))
xhtml (Español (España))

References

Colao A, Zgliczy?ski W, Komorowski J, Kos-Kud?a B, Tabarin A, Kerlan V, et al. Efficacy and safety of high-dose long-acting repeatable octreotide as monotherapy or in combination with pegvisomant or cabergoline in patients with acromegaly not adequately controlled by conventional regimens: results of an open-label, multicentre study. Endokrynol Pol. 2019;70:305-12. https://doi.org/10.5603/EP.a2019.0023

Muhammad A, van der Lely AJ, Delhanty PJ, Dallenga AH, Haitsma IK, Janssen JA, et al. Efficacy and Safety of Switching to Pasireotide in Patients With Acromegaly Controlled With Pegvisomant and First-Generation Somatostatin Analogues (PAPE Study). J Clin Endocrinol Metab. 2018 febr.;103(2):586-95. https://doi.org/10.1210/jc.2017-02017

Trainer PJ, Drake WM, Katznelson L, Freda PU, Herman-Bonert V, van der Lely AJ, et al. Treatment of Acromegaly with the Growth Hormone-Receptor Antagonist Pegvisomant. N Engl J Med. 2000 abr.;342(16):1171-7. https://doi.org/10.1056/NEJM200004203421604

Leonart LP, Tonin FS, Ferreira VL, Fernandez-Llimos F, Pontarolo R. Effectiveness and safety of pegvisomant: a systematic review and meta-analysis of observational longitudinal studies. Endocrine. 2019 en.;63(1):18-26. https://doi.org/10.1007/s12020-018-1729-7

Madsen M, Poulsen PL, Ørskov H, Møller N, Jørgensen JO. Cotreatment with Pegvisomant and a Somatostatin Analog (SA) in SA-Responsive Acromegalic Patients. J Clin Endocrinol Metab. 2011 ag.;96(8):2405-13. https://doi.org/10.1210/jc.2011-0654

Neggers SJ, van Aken MO, de Herder WW, Feelders RA, Janssen JA, Badia X, et al. Quality of life in acromegalic patients during long-term somatostatin analog treatment with and without pegvisomant. J Clin Endocrinol Metab. 2008 oct.;93(10):3853-9. https://doi.org/10.1210/jc.2008-0669

Trainer PJ, Ezzat S, D’Souza GA, Layton G, Strasburger CJ. A randomized, controlled, multicentre trial comparing pegvisomant alone with combination therapy of pegvisomant and long-acting octreotide in patients with acromegaly. Clin Endocrinol (Oxf). 2009 oct.;71(4):549-57. https://doi.org/10.1111/j.1365-2265.2009.03620.x

Ghigo E, Biller BM, Colao A, Kourides IA, Rajicic N, Hutson RK, et al. Comparison of pegvisomant and long-acting octreotide in patients with acromegaly naïve to radiation and medical therapy. J Endocrinol Invest. 2009 dic.;32(11):924-33. https://doi.org/10.1007/BF03345774

Higham CE, Chung TT, Lawrance J, Drake WM, Trainer PJ. Long-term experience of pegvisomant therapy as a treatment for acromegaly. Clin Endocrinol (Oxf). 2009 jul.;71(1):86-91. https://doi.org/10.1111/j.1365-2265.2008.03469.x

van der Lely AJ, Hutson RK, Trainer PJ, Besser GM, Barkan AL, Katznelson L, et al. Long-term treatment of acromegaly with pegvisomant, a growth hormone receptor antagonist. Lancet. 2001 nov.;358(9295):1754-9. https://doi.org/10.1016/S0140-6736(01)06844-1

van der Lely AJ, Bernabeu I, Cap J, Caron P, Colao A, Marek J, et al. Coadministration of lanreotide Autogel and pegvisomant normalizes IGF1 levels and is well tolerated in patients with acromegaly partially controlled by somatostatin analogs alone. Eur J Endocrinol. 2011;164(3):325-33. https://doi.org/10.1530/EJE-10-0867

Neggers SJ, Franck SE, de Rooij FW, Dallenga AH, Poublon RM, Feelders RA, et al. Long-term efficacy and safety of pegvisomant in combination with long-acting somatostatin analogs in acromegaly. J Clin Endocrinol Metab. 2014 oct.;99(10):3644-52. https://doi.org/10.1210/jc.2014-2032

Pivonello R, Galderisi M, Auriemma RS, De Martino MC, Galdiero M, Ciccarelli A, et al. Treatment with Growth Hormone Receptor Antagonist in Acromegaly: Effect on Cardiac Structure and Performance. J Clin Endocrinol Metab. 2007 febr.;92(2):476-82. https://doi.org/10.1210/jc.2006-1587

Baumann G. Growth hormone heterogeneity: genes, isohormones, variants, and binding proteins. Endocr Rev. 1991 nov.;12(4):424-49. https://doi.org/10.1210/edrv-12-4-424

Lu M, Flanagan JU, Langley RJ, Hay MP, Perry JK. Targeting growth hormone function: strategies and therapeutic applications. Signal Transduct Target Ther. 2019;4(1):1-11. https://doi.org/10.1038/s41392-019-0036-y

Petronella N, Drouin G. Gene conversions in the growth hormone gene family of primates: stronger homogenizing effects in the Hominidae lineage. Genomics. 2011 sept.;98(3):173-81. https://doi.org/10.1016/j.ygeno.2011.06.001

Roelfsema F, Biermasz NR, Pereira AM, Romijn J. Nanomedicines in the treatment of acromegaly: focus on pegvisomant. Int J Nanomedicine. 2006;1(4):385-98. https://doi.org/10.2147/nano.2006.1.4.385

Higham CE, Trainer PJ. Growth hormone excess and the development of growth hormone receptor antagonists. Exp Physiol. 2008 nov.;93(11):1157-69. https://doi.org/10.1113/expphysiol.2008.042515

Kaabi Y. Growth hormone and its receptor: A molecular insight. Saudi J Heal Sci. 2012 my.;1(2):61-8. https://doi.org/10.4103/2278-0521.100942

Taylor P, Thankamony GN, Dunger DB, Acerini CL. Pegvisomant: current and potential novel therapeutic applications. Expert Opin Biol Ther. 2009;9(12):1553-63. https://doi.org/10.1517/14712590903449222

Berryman DE, Palmer AJ, Gosney ES, Swaminathan S, DeSantis D, Kopchick JJ. Discovery and uses of pegvisomant: A growth hormone antagonist. Endokrynol Pol. 2007;58(4):322-9.

Drake W, Parkinson C, Besser G, Trainer P. Clinical use of a growth hormone receptor antagonist in the treatment of acromegaly. Trends Endocrinol Metab. 2001 nov.;12(9):408-13. https://doi.org/10.1016/S1043-2760(01)00461-1

Wilkinson IR, Pradhananga SL, Speak R, Artymiuk PJ, Sayers JR, Ross RJ. A long-acting GH receptor antagonist through fusion to GH binding protein. Sci Rep. 2016;6(1):35072. https://doi.org/10.1038/srep35072

Le Roith D, Bondy C, Yakar S, Liu JL, Butler A. The Somatomedin Hypothesis: 2001. Endocr Rev. 2001 febr.;22(1):53-74. https://doi.org/10.1210/edrv.22.1.0419

Casanueva FF. Physiology of Growth Hormone Secretion and Action. Endocrinol Metab Clin North Am. 1992 sept.;21(3):483-517. https://doi.org/10.1016/S0889-8529(18)30199-3

Kopchick JJ, Parkinson C, Stevens EC, Trainer PJ. Growth Hormone Receptor Antagonists: Discovery, Development, and Use in Patients with Acromegaly. Endocr Rev. 2002 oct.;23(5):623-46. https://doi.org/10.1210/er.2001-0022

Kargi AY, Merriam GR. Diagnosis and treatment of growth hormone deficiency in adults. Nat Rev Endocrinol. 2013 jun.;9(6):335-45. https://doi.org/10.1038/nrendo.2013.77

Muller AF, Kopchick JJ, Flyvbjerg A, van der Lely AJ. Growth hormone receptor antagonists. J Clin Endocrinol Metab. 2004 abr.;89(4):1503-11. https://doi.org/10.1210/jc.2002-022049

Bernabeu I, Rodriguez-Gomez IA, Ramos-Levi AM, Marazuela M. Profile of pegvisomant in the management of acromegaly: an evidence-based review of its place in therapy. Res Reports Endocr Disord. 2015 febr.;47. https://doi.org/10.2147/RRED.S78255

Parkinson C, Trainer PJ. Pegvisomant: A growth hormone receptor antagonist for the treatment of acromegaly. Growth Horm IGF Res. 2000;10(supl. B). https://doi.org/10.1016/S1096-6374(00)80023-4

Tritos NA, Biller BM. Pegvisomant: a growth hormone receptor antagonist used in the treatment of acromegaly. Pituitary. 2017;20(1):129-35. https://doi.org/10.1007/s11102-016-0753-y

Ballerini MG, Ropelato MG. El receptor de la hormona de crecimiento humana (hGH) y la proteína de transporte de alta afinidad de la hGH. Rev Argent Endocrinol Metab. 2008;45(1):28-46.

Rinderknecht E, Humbel RE. Polypeptides with nonsuppressible insulin-like and cell-growth promoting activities in human serum: isolation, chemical characterization, and some biological properties of forms I and II. Proc Natl Acad Sci. 1976 jul.;73(7):2365-9. https://doi.org/10.1073/pnas.73.7.2365

Brissenden JE, Ullrich A, Francke U. Human chromosomal mapping of genes for insulin-like growth factors I and II and epidermal growth factor. Nature. 1984 ag.;310(5980):781-4. https://doi.org/10.1038/310781a0

Laron Z. Insulin-like growth factor 1 (IGF-1): a growth hormone. Mol Pathol. 2001 oct.;54(5):311-6. https://doi.org/10.1136/mp.54.5.311

Aguirre GA, De Ita JR, de la Garza RG, Castilla-Cortazar I. Insulin-like growth factor-1 deficiency and metabolic syndrome. J Transl Med. 2016 dic.;14(1):3. https://doi.org/10.1186/s12967-015-0762-z

Lewitt MS. The Role of the Growth Hormone/Insulin-Like Growth Factor System in Visceral Adiposity. Biochem Insights. 2017 en.;10. https://doi.org/10.1177/1178626417703995

Yakar S, Adamo ML. Insulin-like growth factor 1 physiology: lessons from mouse models. Endocrinol Metab Clin North Am. 2012 jun.;41(2):231. https://doi.org/10.1016/j.ecl.2012.04.008

Werner H, Weinstein D, Bentov I. Similarities and differences between insulin and IGF-I: structures, receptors, and signalling pathways. Arch Physiol Biochem. 2008 febr.;114(1):17-22. https://doi.org/10.1080/13813450801900694

Kato H, Faria TN, Stannard B, Roberts CT, LeRoith D. Essential role of tyrosine residues 1131, 1135, and 1136 of the insulin-like growth factor-I (IGF-I) receptor in IGF-I action. Mol Endocrinol. 1994 en.;8(1):40-50. https://doi.org/10.1210/mend.8.1.7512194

Denley A, Cosgrove LJ, Booker GW, Wallace JC, Forbes BE. Molecular interactions of the IGF system. Cytokine Growth Factor Rev. 2005;16(4-5):421-39. https://doi.org/10.1016/j.cytogfr.2005.04.004

Kim JJ, Accili D. Signalling through IGF-I and insulin receptors: where is the specificity? Growth Horm IGF Res. 2002 abr.;12(2):84-90. https://doi.org/10.1054/ghir.2002.0265

Baxter RC. Insulin-like growth factor (IGF)-binding proteins: interactions with IGFs and intrinsic bioactivities. Am J Physiol Endocrinol Metab. 2000 jun.;278(6):E967-76. https://doi.org/10.1152/ajpendo.2000.278.6.E967

Firth SM, Baxter RC. Cellular actions of the insulin-like growth factor binding proteins. Endocr Rev. 2002 dic.;23(6):824-54. https://doi.org/10.1210/er.2001-0033

Lewitt MS, Saunders H, Phuyal JL, Baxter RC. Complex formation by human insulin-like growth factor-binding protein-3 and human acid-labile subunit in growth hormone-deficient rats. Endocrinology. 1994 jun.;134(6):2404-9. https://doi.org/10.1210/endo.134.6.7514998

Clemmons DR, Underwood LE. Nutritional Regulation of IGF-I and IGF Binding Proteins. Annu Rev Nutr. 1991 jul.;11(1):393-412. https://doi.org/10.1146/annurev.nu.11.070191.002141

Kanety H, Karasik A, Klinger B, Silbergeld A, Laron Z. Long-term treatment of Laron type dwarfs with insulin-like growth factor-1 increases serum insulin-like growth factor-binding protein-3 in the absence of growth hormone activity. Acta Endocrinol (Copenh). 1993 febr.;128(2):144-9. https://doi.org/10.1530/acta.0.1280144

Chen WY, Wight DC, Wagner TE, Kopchick JJ. Expression of a mutated bovine growth hormone gene suppresses growth of transgenic mice. Proc Natl Acad Sci USA. 1990 jul.;87(13):5061-5. https://doi.org/10.1073/pnas.87.13.5061

Chen WY, Wight DC, Chen NY, Coleman TA, Wagner TE, Kopchick JJ. Mutations in the third alpha-helix of bovine growth hormone dramatically affect its intracellular distribution in vitro and growth enhancement in transgenic mice. J Biol Chem. 1991 febr.;266(4):2252-8. https://doi.org/10.1016/S0021-9258(18)52236-5

Fuh G, Cunningham BC, Fukunaga R, Nagata S, Goeddel D V, Wells JA. Rational design of potent antagonists to the human growth hormone receptor. Science. 1992 jun.;256(5064):1677-80. https://doi.org/10.1126/science.256.5064.1677

Lowman HB, Wells JA. Affinity maturation of human growth hormone by monovalent phage display. J Mol Biol. 1993 dic.;234(3):564-78. https://doi.org/10.1006/jmbi.1993.1612

Ross RJ, Leung KC, Maamra M, Bennett W, Doyle N, Waters MJ, et al. 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 Dimer1. J Clin Endocrinol Metab. 2001 abr.;86(4):1716-23. https://doi.org/10.1210/jcem.86.4.7403

Pradhananga S, Wilkinson I, Ross RJ. Pegvisomant: structure and function. J Mol Endocrinol. 2002;29(1):11-4. https://doi.org/10.1677/jme.0.0290011

EMEA. Eurpoean Public Assessment Reports for authorised medicinal products for human use; Somavert (Scientific Discussion). European Medicines Agency; 2004.

Chen WY, Chen NY, Yun J, Wagner TE, Kopchick JJ. In vitro and in vivo studies of antagonistic effects of human growth hormone analogs. J Biol Chem. 1994 jun.;269(22):15892-7. https://doi.org/10.1016/S0021-9258(17)40764-2

Muller-Bolla M, Courson F, Smail-Faugeron V, Bernardin T, Lupi-Pégurier L. Dental erosion in French adolescents. BMC Oral Health. 2015;15(1). https://doi.org/10.1186/s12903-015-0133-4

Davis FF, Abuchowski A, Van Es T, Palczuk NC, Chen R, Savoca K, et al. Enzyme-polyethylene glycol adducts: modified enzymes with unique properties. En: Enzyme Engineering. Springer; 1978. p. 169-73.

Clark R, Olson K, Fuh G, Marian M, Mortensen D, Teshima G, et al. Long-acting growth hormones produced by conjugation with polyethylene glycol. J Biol Chem. 1996 sept.;271(36):21969-77. https://doi.org/10.1074/jbc.271.36.21969

Tritos NA, Biller BM. Pegvisomant: a growth hormone receptor antagonist used in the treatment of acromegaly. Pituitary. 2017;20(1):129-35. https://doi.org/10.1007/s11102-016-0753-y

Harris JM, Martin NE, Modi M. Pegylation: a novel process for modifying pharmacokinetics. Clin Pharmacokinet. 2001;40(7):539-51. https://doi.org/10.2165/00003088-200140070-00005

Veldhuis JD, Bidlingmaier M, Bailey J, Erickson D, Sandroni P. A pegylated growth hormone receptor antagonist, pegvisomant, does not enter the brain in humans. J Clin Endocrinol Metab. 2010 ag.;95(8):3844-7. https://doi.org/10.1210/jc.2010-0538

Rodvold KA, Van der Lely AJ. Pharmacokinetics and pharmacodynamics of B2036-PEG, a novel growth hormone receptor antagonist, in acromegalic subjects. En: Endocrine Society 81st Annual Meeting; 1999.

Jehle S, Reyes CM, Sundeen RE, Freda PU. Alternate-day administration of pegvisomant maintains normal serum insulin-like growth factor-I levels in patients with acromegaly. J Clin Endocrinol Metab. 2005 mzo.;90(3):1588-93. https://doi.org/10.1210/jc.2004-1967

Higham CE, Thomas JD, Bidlingmaier M, Drake WM, Trainer PJ. Successful use of weekly pegvisomant administration in patients with acromegaly. Eur J Endocrinol. 2009 jul.;161(1):21-5. https://doi.org/10.1530/EJE-08-0990

Parkinson C, Burman P, Messig M, Trainer PJ. Gender, Body Weight, Disease Activity, and Previous Radiotherapy Influence the Response to Pegvisomant. J Clin Endocrinol Metab. 2007 en.;92(1):190-5. https://doi.org/10.1210/jc.2006-1412

Buchfelder M, van der Lely AJ, Biller BM, Webb SM, Brue T, Strasburger CJ, et al. Long-term treatment with pegvisomant: observations from 2090 acromegaly patients in Acrostudy. Eur J Endocrinol. 2018 dic.;179(6):419-27. https://doi.org/10.1530/EJE-18-0616

Boguszewski CL, Huayllas MK, Vilar L, Naves LA, Ribeiro-Oliveira A, Soares BS, et al. Brazilian multicenter study on pegvisomant treatment in acromegaly. Arch Endocrinol Metab. 2019 jul.;63(4). https://doi.org/10.20945/2359-3997000000159

Basavilbaso NX, Ballarino MC, Bruera D, Bruno OD, Chervin AB, Danilowicz K, et al. Pegvisomant in acromegaly: a multicenter real-life study in Argentina. Arch Endocrinol Metab. 2019 ag.;63(4):320-7. https://doi.org/10.20945/2359-3997000000160

Feenstra J, de Herder WW, ten Have SM, van den Beld AW, Feelders RA, Janssen JA, et al. Combined therapy with somatostatin analogues and weekly pegvisomant in active acromegaly. Lancet. 2005 my.;365(9471):1644-6. https://doi.org/10.1016/S0140-6736(05)63011-5

Neggers SJ, van Aken MO, Janssen JA, Feelders RA, de Herder WW, van der Lely AJ. Long-term efficacy and safety of combined treatment of somatostatin analogs and pegvisomant in acromegaly. J Clin Endocrinol Metab. 2007 dic.;92(12):4598-601. https://doi.org/10.1210/jc.2007-1234

Bonert V, Mirocha J, Carmichael J, Yuen KC, Araki T, Melmed S. Cost-Effectiveness and Efficacy of a Novel Combination Regimen in Acromegaly: A Prospective, Randomized Trial. J Clin Endocrinol Metab. 2020 sept. 1;105(9):e3236-45. https://doi.org/10.1210/clinem/dgaa444

Higham CE, Atkinson AB, Aylwin S, Bidlingmaier M, Drake WM, Lewis A, et al. Effective Combination Treatment with Cabergoline and Low-Dose Pegvisomant in Active Acromegaly: A Prospective Clinical Trial. J Clin Endocrinol Metab. 2012 abr.;97(4):1187-93. https://doi.org/10.1210/jc.2011-2603

Neggers SJ, Muhammad A, van der Lely AJ. Pegvisomant Treatment in Acromegaly. Neuroendocrinology. 2016;103(1):59-65. https://doi.org/10.1159/000381644

van der Lely AJ, Biller BM, Brue T, Buchfelder M, Ghigo E, Gomez R, et al. Long-Term Safety of Pegvisomant in Patients with Acromegaly: Comprehensive Review of 1288 Subjects in Acrostudy. J Clin Endocrinol Metab. 2012 my.;97(5):1589-97. https://doi.org/10.1210/jc.2011-2508

Giustina A. Optimal use of pegvisomant in acromegaly: are we getting there? Endocrine. 2015;48(1):3-8. https://doi.org/10.1007/s12020-014-0462-0

Giustina A, Ambrosio MR, Beck-Peccoz P, Bogazzi F, Cannavo’ S, De Marinis L, et al. Use of Pegvisomant in acromegaly. An Italian Society of Endocrinology guideline. J Endocrinol Invest. 2014 oct.;37(10):1017-30. https://doi.org/10.1007/s40618-014-0146-x

Giustina A, Arnaldi G, Bogazzi F, Cannavò S, Colao A, De Marinis L, et al. Pegvisomant in acromegaly: an update. J Endocrinol Invest. 2017 jun.;40(6):577-89. https://doi.org/10.1007/s40618-017-0614-1

Paisley AN, Trainer P, Drake W, Paisley AN, Trainer P, Drake W. Pegvisomant: a novel pharmacotherapy for the treatment of acromegaly. Expert Opin Biol Ther. 2004;4(3). https://doi.org/10.1517/14712598.4.3.421

van der Lely AJ, Muller AF, Janssen JA, Davis RJ, Zib KA, Scarlett JA, et al. Control of Tumor Size and Disease Activity during Cotreatment with Octreotide and the Growth Hormone Receptor Antagonist Pegvisomant in an Acromegalic Patient. J Clin Endocrinol Metab. 2001 febr.;86(2):478-81. https://doi.org/10.1210/jcem.86.2.7206

Buhk JH, Jung S, Psychogios MN, Göricke S, Hartz S, Schulz-Heise S, et al. Tumor volume of growth hormone-secreting pituitary adenomas during treatment with pegvisomant: a prospective multicenter study. J Clin Endocrinol Metab. 2010 febr.;95(2):552-8. https://doi.org/10.1210/jc.2009-1239

Jiménez C, Burman P, Abs R, Clemmons DR, Drake WM, Hutson KR, et al. Follow-up of pituitary tumor volume in patients with acromegaly treated with pegvisomant in clinical trials. Eur J Endocrinol. 2008 nov.;159(5):517-23. https://doi.org/10.1530/EJE-08-0205

Buchfelder M, Weigel D, Droste M, Mann K, Saller B, Brübach K, et al. Pituitary tumor size in acromegaly during pegvisomant treatment: experience from MR re-evaluations of the German Pegvisomant Observational Study. Eur J Endocrinol. 2009;161(1):27-35. https://doi.org/10.1530/EJE-08-0910

Marazuela M, Lucas T, Alvarez-Escolá C, Puig-Domingo M, de la Torre NG, de Miguel-Novoa P, et al. Long-term treatment of acromegalic patients resistant to somatostatin analogues with the GH receptor antagonist pegvisomant: its efficacy in relation to gender and previous radiotherapy. Eur J Endocrinol. 2009 abr.;160(4):535-42. https://doi.org/10.1530/EJE-08-0705

Marazuela M, Paniagua AE, Gahete MD, Lucas T, Alvarez-Escolá C, Manzanares R, et al. Somatotroph tumor progression during pegvisomant therapy: a clinical and molecular study. J Clin Endocrinol Metab. 2011 febr.;96(2):E251-9. https://doi.org/10.1210/jc.2010-1742

Giustina A, Barkhoudarian G, Beckers A, Ben-Shlomo A, Biermasz N, Biller B, et al. Multidisciplinary management of acromegaly: A consensus. Rev Endocr Metab Disord. 2020;21(4):667-78. https://doi.org/10.1007/s11154-020-09588-z

Creative Commons License

This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.

Dimensions


PlumX


Downloads

Download data is not yet available.