=====Pegvisomant=====
Pegvisomant is a protein containing 191 amino acid residues to which several polyethylene glycol polymers have been covalently bound in order to slow clearance from the blood. The protein is a modified version of human [[growth hormone]] designed to bind to and block the growth hormone receptor. It is manufactured using genetically modified E. coli bacteria. The polyethylene glycol polymers are subsequently added chemically.

===== Indications =====

The FDA approved pegvisomant (Somavert Pfizer), a [[growth hormone]] receptor antagonist, for parenteral treatment of [[acromegaly]] in patients who are not candidates for or have had an inadequate response to surgery or other treatment
((Pegvisomant (Somavert) for Acromegaly.The Medical Letter on Drugs and Therapeutics.1160c.45.55-56)).

As the only GH receptor antagonist (GHRA) available, pegvisomant has shown its effectiveness in the control of [[insulin like growth factor]] [[IGF-1]]
((Neggers SJ, van Aken MO, de Herder WW, et al. Quality of life in acromegalic patients during long-term somatostatin analog treatment with and without pegvisomant. J Clin Endocrinol Metab. 2008;93(10):3853–3859.)).

van der Lely et al demonstrated Pegvisomant as an effective medical treatment for [[acromegaly]], because of the patients treated for 12 months or more, 87 of 90 (97%) achieved a normal serum IGF-1 concentration
((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. Long-term treatment of
acromegaly with pegvisomant, a growth hormone receptor antagonist. Lancet. 2001
Nov 24;358(9295):1754-9. PubMed PMID: 11734231.)).

It is delivered as a powder that is mixed with water and injected under the skin.
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Data support a comparable [[QoL]] in patients receiving [[pegvisomant]] vs. [[somatostatin analogue]], despite the fact that the vast majority receiving pegvisomant did not respond to or were not able to tolerate somatostatin analogs
((Dichtel LE, Kimball A, Yuen KCJ, et al. Effects of Growth Hormone Receptor Antagonism and Somatostatin Analog Administration on Quality of Life in Acromegaly [published online ahead of print, 2020 Aug 10]. Clin Endocrinol (Oxf). 2020;10.1111/cen.14309. doi:10.1111/cen.14309)).
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Despite the more aggressive behavior of GH&[[PRL]]-[[PitNET]]s compared to [[Somatotroph pituitary neuroendocrine tumor]]s, there were no significant differences in the rate of [[IGF-1]] control between the two drugs ([[pegvisomant]] and [[pasireotide]]) in either patient group.
Both drugs were effective in controlling IGF-1 and [[PRL]] hypersecretion in the tumors studied.
The study found that pegvisomant and pasireotide are both effective treatments for controlling IGF-1 and PRL hypersecretion in patients with GH&PRL-Pit-NETs and GH-Pit-NETs, with no substantial differences in efficacy between the two drugs
((Araujo-Castro M, Biagetti B, Menéndez Torre E, Novoa-Testa I, Cordido F, Pascual-Corrales E, Rodríguez Berrocal V, Guerrero-Pérez F, Vicente A, Percovich Hualpa JC, García-Centeno R, González-Fernández L, Ollero García MD, Irigaray Echarri A, Moure Rodríguez MD, Novo-Rodríguez C, Calatayud M, Villar-Taibo R, Bernabéu I, Alvarez-Escola C, Benítez Valderrama P, Tenorio-Jiménez C, Abellán Galiana P, Venegas E, González-Molero I, Iglesias P, Blanco-Carrera C, Vidal-Ostos De Lara F, de Miguel Novoa P, López Mezquita E, Hanzu FA, Aldecoa I, Aznar S, Lamas C, Aulinas A, Asla Q, Gracia Gimeno P, Recio-Córdova JM, Avilés-Pérez MD, Asensio-Wandosell D, Sampedro-Núñez M, Cámara R, Paja Fano M, Ruz-Caracuel I, Fajardo C, Marazuela M, Puig-Domingo M. [[Pegvisomant]] and [[pasireotide]] in [[PRL]] and [[GH]] co-secreting vs [[GH]]-secreting [[Pit-NET]]s. Endocr Relat Cancer. 2024 May 27;31(7):e240043. doi: 10.1530/ERC-24-0043. PMID: 38713182.)).

====Side effects====
Side effects of Pegvisomant include reactions at the injection site, swelling of the limbs, chest pain, hypoglycemia, nausea and hepatitis.

Blocking of the growth hormone's receptor reduces feedback control of the growth hormone regulation leading to approximately doubled GH levels.

The GH receptor antagonist pegvisomant is increasingly used as therapy in acromegaly. 

====Combination Therapy====

The combination of [[somatostatin analog]] SA and pegvisomant in patients who could not achieve IGF-1 normalization was safe and aided improved quality of life in [[acromegaly]]
((Fendri S, Karaca P, Tiev E, Buchfelder M, Lalau J. Control of disease activity and tumor size after introduction of pegvisomant in a lanreotide-resistant acromegalic patient. Ann Endocrinol (Paris) 2013;74(1):49–52. [PubMed]))
((Neggers SJ, de Herder WW, Feelders RA, van der Lely AJ. Conversion of daily pegvisomant to weekly pegvisomant combined with long-acting somatostatin analogs, in controlled acromegaly patients. Pituitary. 2011;14(3):253–258. [PMC free article] [PubMed]))
((Madsen M, Poulsen PL, Orskov H, Møller N, Jørgensen JO. Cotreatment with pegvisomant and a somatostatin analog (SA) in SA-responsive acromegalic patients. J Clin Endocrinol Metab. 2011;96(8):2405–2413. [PubMed]))
((van der Lely A, Bernabeu I, Cap 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):325–333.)).

Further, the combination of pegvisomant and SA could reduce the dose of SA that is required
((Madsen M, Poulsen PL, Orskov H, Møller N, Jørgensen JO. Cotreatment with pegvisomant and a somatostatin analog (SA) in SA-responsive acromegalic patients. J Clin Endocrinol Metab. 2011;96(8):2405–2413.)).

There is, however, no evidence adequate to prove the significant benefits obtained from combination
((Madsen M, Poulsen PL, Orskov H, Møller N, Jørgensen JO. Cotreatment with pegvisomant and a somatostatin analog (SA) in SA-responsive acromegalic patients. J Clin Endocrinol Metab. 2011;96(8):2405–2413.)).

In Melmed et al’s guidelines, such combination is recommended on the condition that patients are resistant to other treatments
((Melmed S, Colao A, Barkan A, et al. Acromegaly Consensus Group Guidelines for acromegaly management: an update. J Clin Endocrinol Metab. 2009;94(5):1509–1517.)).

In combination with cabergoline, the combination of SA and cabergoline might provide effective treatment in patients with mixed pituitary neuroendocrine tumors in whom simultaneously elevated prolactin (PRL) and GH are observed
((Sowiń ski J, Sawicka N, Piatek K, Zybek A, Ruchala M. Pharmacoeconomic aspects of the treatment of pituitary gland tumours. Contemp Oncol (Pozn) 2013;17(2):137–143.)),
while, in patients who are partially responsive to the maximum SA dose, additive therapy with cabergoline could normalize IGF-1 in about half of the patients, including those without prolactinemia
((Sandret L, Maison P, Chanson P. Place of cabergoline in acromegaly: a meta-analysis. J Clin Endocrinol Metab. 2011;96(5):1327–1335.)).

Pituitary surgery might be indicated on pegvisomant treatment, due to side effects, adenoma growth or intention to cure after primary treatment.