A Pituitary Society update to acromegaly management guidelines

Pituitary - Tập 24 Số 1 - Trang 1-13 - 2021
Maria Fleseriu1, Beverly M. K. Biller2, Pamela U. Freda3, Mônica R. Gadelha4, Andrea Giustina5, Laurence Katznelson6, Mark E. Molitch7, Susan L. Samson8, Christian J. Strasburger9, Aart‐Jan van der Lely10, Шломо Мелмед11
1Pituitary Center, Departments of Medicine and Neurological Surgery, Oregon Health & Science University, Portland, OR, USA
2Neuroendocrine Unit, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA
3Department of Medicine, Columbia University, Vagelos College of Physicians and Surgeons, New York, NY, USA
4Neuroendocrinology Research Center/Endocrinology Section, Medical School and Hospital Universitário Clementino Fraga Filho, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil
5Institute of Endocrine and Metabolic Sciences, San Raffaele Vita-Salute University and IRCCS San Raffaele Hospital, Milan, Italy
6Departments of Medicine and Neurosurgery, Stanford University School of Medicine, Stanford, CA, USA
7Division of Endocrinology, Metabolism & Molecular Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL, USA
8Pituitary Center, Departments of Medicine and Neurosurgery, Baylor College of Medicine, Houson, TX, USA
9Department of Medicine for Endocrinology, Diabetes and Nutritional Medicine, Charité Universitätsmedizin, Berlin, Germany
10Pituitary Center Rotterdam, Endocrinology Section, Department of Internal Medicine, Erasmus University Medical Center, Rotterdam, The Netherlands
11Pituitary Center, Cedars-Sinai Medical Center, 8700 Beverly Blvd., Room 2015, Los Angeles, CA, 90048, USA

Tóm tắt

Abstract

Guidelines and consensus statements ensure that physicians managing acromegaly patients have access to current information on evidence-based treatments to optimize outcomes. Given significant novel recent advances in understanding acromegaly natural history and individualized therapies, the Pituitary Society invited acromegaly experts to critically review the current literature in the context of Endocrine Society guidelines and Acromegaly Consensus Group statements. This update focuses on how recent key advances affect treatment decision-making and outcomes, and also highlights the likely role of recently FDA-approved therapies as well as novel combination therapies within the treatment armamentarium.

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Tài liệu tham khảo

Katznelson L, Laws ER Jr, Melmed S, Molitch ME, Murad MH, Utz A et al (2014) Acromegaly: an endocrine society clinical practice guideline. J Clin Endocrinol Metab 99(11):3933–3951. https://doi.org/10.1210/jc.2014-2700

Giustina A, Chanson P, Kleinberg D, Bronstein MD, Clemmons DR, Klibanski A et al (2014) Expert consensus document: a consensus on the medical treatment of acromegaly. Nat Rev Endocrinol 10(4):243–248. https://doi.org/10.1038/nrendo.2014.21

Melmed S, Bronstein MD, Chanson P, Klibanski A, Casanueva FF, Wass JAH et al (2018) A Consensus Statement on acromegaly therapeutic outcomes. Nat Rev Endocrinol 14(9):552–561. https://doi.org/10.1038/s41574-018-0058-5

Samson SL, Nachtigall LB, Fleseriu M, Gordon MB, Bolanowski M, Labadzhyan A et al (2020) Maintenance of acromegaly control in patients switching from injectable somatostatin receptor ligands to oral octreotide therapy. J Clin Endocrinol Metab. https://doi.org/10.1210/clinem/dgaa526

Heck A, Emblem KE, Casar-Borota O, Bollerslev J, Ringstad G (2016) Quantitative analyses of T2-weighted MRI as a potential marker for response to somatostatin analogs in newly diagnosed acromegaly. Endocrine 52(2):333–343. https://doi.org/10.1007/s12020-015-0766-8

Brzana J, Yedinak CG, Gultekin SH, Delashaw JB, Fleseriu M (2013) Growth hormone granulation pattern and somatostatin receptor subtype 2A correlate with postoperative somatostatin receptor ligand response in acromegaly: a large single center experience. Pituitary 16(4):490–498. https://doi.org/10.1007/s11102-012-0445-1

MYCAPSSA [prescribing information]. Needham, MA: Chiasma, Inc.; 2020.

Samson SL, Nachtigall LB, Fleseriu M, Gordon MB, Bolanowski M, Labadzhyan A et al (2020) Results from the phase 3, randomized, double-blind, placebo-controlled OPTIMAL study of oral octreotide capsules in adult patients with acromegaly. Endocrine Abstracts 70(OC4):6. https://doi.org/10.1530/endoabs.70.OC4.6

Melmed S, Popovic V, Bidlingmaier M, Mercado M, van der Lely AJ, Biermasz N et al (2015) Safety and efficacy of oral octreotide in acromegaly: results of a multicenter phase III trial. J Clin Endocrinol Metab 100(4):1699–1708. https://doi.org/10.1210/jc.2014-4113

Samson SL, Nachtigall LB, Fleseriu M, Ur E, Ludlam WH, Patou G et al (2020) IGF-I variability and its association with demographic and clinical characteristics in patients with acromegaly treated with injectable somatostatin receptor ligands: results from an international prospective phase III study. J Endocr. Soc. https://doi.org/10.1210/jendso/bvaa046.1907

Fleseriu M, Fogelfeld L, Gordon MB, Sisco J, Crosby RD, Ludlam WH et al (2020) An evaluation of the Acromegaly Treatment Satisfaction Questionnaire (Acro-TSQ) in adult patients with acromegaly, including correlations with other patient-reported outcome measures: data from two large multicenter international studies. Pituitary 23(4):347–358. https://doi.org/10.1007/s11102-020-01038-y

Geer EB, Sisco J, Adelman DT, Ludlam WH, Haviv A, Gelbaum D et al (2020) Observed discordance between outcomes reported by acromegaly patients and their treating endocrinology medical provider. Pituitary 23(2):140–148. https://doi.org/10.1007/s11102-019-01013-2

Strasburger CJ, Karavitaki N, Stormann S, Trainer PJ, Kreitschmann-Andermahr I, Droste M et al (2016) Patient-reported outcomes of parenteral somatostatin analogue injections in 195 patients with acromegaly. Eur J Endocrinol 174(3):355–362. https://doi.org/10.1530/EJE-15-1042

Tuvia S, Atsmon J, Teichman SL, Katz S, Salama P, Pelled D et al (2012) Oral octreotide absorption in human subjects: comparable pharmacokinetics to parenteral octreotide and effective growth hormone suppression. J Clin Endocrinol Metab 97(7):2362–2369. https://doi.org/10.1210/jc.2012-1179

Park KH, Lee EJ, Seo GH, Ku CR (2020) Risk for acromegaly-related comorbidities by sex in korean acromegaly. J Clin Endocrinol Metab. https://doi.org/10.1210/clinem/dgz317

Burton T, Le Nestour E, Neary M, Ludlam WH (2016) Incidence and prevalence of acromegaly in a large US health plan database. Pituitary 19(3):262–267. https://doi.org/10.1007/s11102-015-0701-2

Tjornstrand A, Gunnarsson K, Evert M, Holmberg E, Ragnarsson O, Rosen T et al (2014) The incidence rate of pituitary adenomas in western Sweden for the period 2001–2011. Eur J Endocrinol 171(4):519–526. https://doi.org/10.1530/EJE-14-0144

Lenders NF, McCormack AI, Ho KKY (2020) MANAGEMENT OF ENDOCRINE DISEASE: does gender matter in the management of acromegaly? Eur J Endocrinol 182(5):R67–R82. https://doi.org/10.1530/EJE-19-1023

Gadelha MR, Kasuki L, Lim DST, Fleseriu M (2019) Systemic complications of acromegaly and the impact of the current treatment landscape: an update. Endocr Rev 40(1):268–332. https://doi.org/10.1210/er.2018-00115

Ambrosio MR, Gagliardi I, Chiloiro S, Ferreira AG, Bondanelli M, Giampietro A et al (2020) Acromegaly in the elderly patients. Endocrine 68(1):16–31. https://doi.org/10.1007/s12020-020-02206-7

Maione L, Brue T, Beckers A, Delemer B, Petrossians P, Borson-Chazot F et al (2017) Changes in the management and comorbidities of acromegaly over three decades: the French Acromegaly Registry. Eur J Endocrinol 176(5):645–655. https://doi.org/10.1530/EJE-16-1064

Colao A, Grasso LFS, Di Cera M, Thompson-Leduc P, Cheng WY, Cheung HC et al (2020) Association between biochemical control and comorbidities in patients with acromegaly: an Italian longitudinal retrospective chart review study. J Endocrinol Invest 43(4):529–538. https://doi.org/10.1007/s40618-019-01138-y

Wang Z, Gao L, Guo X, Feng C, Deng K, Lian W et al (2019) Preoperative fasting C-peptide acts as a promising predictor of improved glucose tolerance in patients with acromegaly after transsphenoidal surgery: a retrospective study of 64 cases from a large pituitary center in China. Front Endocrinol (Lausanne) 10:736. https://doi.org/10.3389/fendo.2019.00736

Mazziotti G, Lania A, Canalis E (2019) MANAGEMENT OF ENDOCRINE DISEASE: Bone disorders associated with acromegaly: mechanisms and treatment. Eur J Endocrinol 181(2):R45–R56. https://doi.org/10.1530/EJE-19-0184

Chiloiro S, Giampietro A, Frara S, Bima C, Donfrancesco F, Fleseriu CM et al (2020) Effects of pegvisomant and pasireotide LAR on vertebral fractures in acromegaly resistant to first-generation SRLs. J Clin Endocrinol Metab. https://doi.org/10.1210/clinem/dgz054

Mazziotti G, Battista C, Maffezzoni F, Chiloiro S, Ferrante E, Prencipe N et al (2020) Treatment of acromegalic osteopathy in real-life clinical practice: the BAAC (Bone Active Drugs in Acromegaly) study. J Clin Endocrinol Metab. https://doi.org/10.1210/clinem/dgaa363

Giustina A (2020) Acromegaly and vertebral fractures: facts and questions. Trends Endocrinol Metab 31(4):274–275. https://doi.org/10.1016/j.tem.2020.01.011

Duarte FH, Jallad RS, Bronstein MD (2015) Clomiphene citrate for treatment of acromegaly not controlled by conventional therapies. J Clin Endocrinol Metab 100(5):1863–1869. https://doi.org/10.1210/jc.2014-3913

Pelsma ICM, Biermasz NR, Pereira AM, van Furth WR, Appelman-Dijkstra NM, Kloppenburg M et al (2020) Progression of vertebral fractures in long-term controlled acromegaly: a 9-year follow-up study. Eur J Endocrinol 183(4):427–437. https://doi.org/10.1530/eje-20-0415

Parolin M, Dassie F, Alessio L, Wennberg A, Rossato M, Vettor R et al (2020) Obstructive sleep apnea in acromegaly and the effect of treatment: a systematic review and meta-analysis. J Clin Endocrinol Metab. https://doi.org/10.1210/clinem/dgz116

Wolters TLC, Roerink S, Drenthen LCA, van Haren-Willems J, Wagenmakers M, Smit JWA et al (2020) The course of obstructive sleep apnea syndrome in patients with acromegaly during treatment. J Clin Endocrinol Metab. https://doi.org/10.1210/clinem/dgz050

Wolters TLC, Roerink S, Sterenborg R, Wagenmakers M, Husson O, Smit JWA et al (2020) The effect of treatment on quality of life in patients with acromegaly: a prospective study. Eur J Endocrinol 182(3):319–331. https://doi.org/10.1530/EJE-19-0732

Wajnrajch M, Gomez R, Hey-Hadavi J, Kelepouris N, Lans J, Loftus J et al (2019) ACROSTUDY: Safety and efficacy of a cohort of 110 naïve patients with acromegaly treated with pegvisomant. J Endocr Soc. https://doi.org/10.1210/js.2019-SUN-LB080

Jackson Y, Flood E, Rhoten S, Janssen EM, Lundie M (2019) AcroVoice: eliciting the patients' perspective on acromegaly disease activity. Pituitary 22(1):62–69. https://doi.org/10.1007/s11102-018-00933-9

Fleseriu M, Fogelfeld L, Gordon MB, Sisco J, Colwell HH, Ludlam WH et al (2019) Development of a novel patient-reported measure for acromegaly: the Acro-TSQ. Pituitary 22(6):581–593. https://doi.org/10.1007/s11102-019-00986-4

Kreitschmann-Andermahr I, Buchfelder M, Kleist B, Kohlmann J, Menzel C, Buslei R et al (2017) Predictors of quality of life in 165 patients with acromegaly: results from a single-center study. Endocr Pract 23(1):79–88. https://doi.org/10.4158/EP161373.OR

Fujio S, Arimura H, Hirano H, Habu M, Bohara M, Moinuddin FM et al (2017) Changes in quality of life in patients with acromegaly after surgical remission: a prospective study using SF-36 questionnaire. Endocr J 64(1):27–38. https://doi.org/10.1507/endocrj.EJ16-0182

Kasuki L, Rocha PDS, Lamback EB, Gadelha MR (2019) Determinants of morbidities and mortality in acromegaly. Arch Endocrinol Metab 63(6):630–637. https://doi.org/10.20945/2359-3997000000193

Bolfi F, Neves AF, Boguszewski CL, Nunes-Nogueira VS (2018) Mortality in acromegaly decreased in the last decade: a systematic review and meta-analysis. Eur J Endocrinol 179(1):59–71. https://doi.org/10.1530/EJE-18-0255

Esposito D, Ragnarsson O, Granfeldt D, Marlow T, Johannsson G, Olsson DS (2018) Decreasing mortality and changes in treatment patterns in patients with acromegaly from a nationwide study. Eur J Endocrinol 178(5):459–469. https://doi.org/10.1530/EJE-18-0015

Arosio M, Reimondo G, Malchiodi E, Berchialla P, Borraccino A, De Marinis L et al (2012) Predictors of morbidity and mortality in acromegaly: an Italian survey. Eur J Endocrinol 167(2):189–198. https://doi.org/10.1530/EJE-12-0084

Wu JC, Huang WC, Chang HK, Ko CC, Lirng JF, Chen YC (2019) Natural history of acromegaly: incidences, re-operations, cancers, and mortality rates in a national cohort. Neuroendocrinology 110:977–987. https://doi.org/10.1159/000505332

Lai NB, Garg D, Heaney AP, Bergsneider M, Leung AM (2020) No benefit of dedicated thyroid nodule screening in patients with acromegaly. Endocr Pract 26(1):16–21. https://doi.org/10.4158/EP-2019-0254

Ochiai Y, Inoshita N, Iizuka T, Nishioka H, Yamada S, Kitagawa M et al (2020) Clinicopathological features of colorectal polyps and risk of colorectal cancer in acromegaly. Eur J Endocrinol 182(3):313–318. https://doi.org/10.1530/EJE-19-0813

Schilbach K, Gar C, Lechner A, Nicolay SS, Schwerdt L, Haenelt M et al (2019) Determinants of the growth hormone nadir during oral glucose tolerance test in adults. Eur J Endocrinol 181(1):55–67. https://doi.org/10.1530/EJE-19-0139

Schilbach K, Bidlingmaier M (2019) Laboratory investigations in the diagnosis and follow-up of GH-related disorders. Arch Endocrinol Metab 63(6):618–629. https://doi.org/10.20945/2359-3997000000192

Neidert MC, Sze L, Zwimpfer C, Sarnthein J, Seifert B, Frei K et al (2013) Soluble alpha-klotho: a novel serum biomarker for the activity of GH-producing pituitary adenomas. Eur J Endocrinol 168(4):575–583. https://doi.org/10.1530/EJE-12-1045

Schweizer J, Haenelt M, Schilbach K, Giannetti A, Bizzi M, Rocha B et al (2019) Alpha Klotho as a marker of disease activity in acromegaly. J Endocr Soc. https://doi.org/10.1210/js.2019-OR32-2

Coopmans EC, El-Sayed N, Frystyk J, Magnusson NE, Jorgensen JOL, van der Lely AJ et al (2020) Soluble Klotho: a possible predictor of quality of life in acromegaly patients. Endocrine 69(1):165–174. https://doi.org/10.1007/s12020-020-02306-4

Feelders RA, Bidlingmaier M, Strasburger CJ, Janssen JA, Uitterlinden P, Hofland LJ et al (2005) Postoperative evaluation of patients with acromegaly: clinical significance and timing of oral glucose tolerance testing and measurement of (free) insulin-like growth factor I, acid-labile subunit, and growth hormone-binding protein levels. J Clin Endocrinol Metab 90(12):6480–6489. https://doi.org/10.1210/jc.2005-0901

Donegan D, Algeciras-Schimnich A, Erickson DZ (2020) IGF-1 in the early post-operative assessment of acromegaly. J Endocr Soc. https://doi.org/10.1210/jendso/bvaa046.287

Park SH, Ku CR, Moon JH, Kim EH, Kim SH, Lee EJ (2018) Age- and sex-specific differences as predictors of surgical remission among patients with acromegaly. J Clin Endocrinol Metab 103(3):909–916. https://doi.org/10.1210/jc.2017-01844

Ioachimescu AG, Handa T, Goswami N, Pappy AL 2nd, Veledar E, Oyesiku NM (2020) Gender differences and temporal trends over two decades in acromegaly: a single center study in 112 patients. Endocrine 67(2):423–432. https://doi.org/10.1007/s12020-019-02123-4

Agrawal N, Ioachimescu AG (2020) Prognostic factors of biochemical remission after transsphenoidal surgery for acromegaly: a structured review. Pituitary 23(5):582–594. https://doi.org/10.1007/s11102-020-01063-x

Spina A, Losa M, Mortini P (2019) Pituitary adenomas in elderly patients: clinical and surgical outcome analysis in a large series. Endocrine 65(3):637–645. https://doi.org/10.1007/s12020-019-01959-0

Jane JA Jr, Starke RM, Elzoghby MA, Reames DL, Payne SC, Thorner MO et al (2011) Endoscopic transsphenoidal surgery for acromegaly: remission using modern criteria, complications, and predictors of outcome. J Clin Endocrinol Metab 96(9):2732–2740. https://doi.org/10.1210/jc.2011-0554

Sasagawa Y, Hayashi Y, Tachibana O, Nakagawa A, Oishi M, Takamura T et al (2018) Transsphenoidal surgery for elderly patients with acromegaly and its outcomes: comparison with younger patients. World Neurosurg 118:e229–e234. https://doi.org/10.1016/j.wneu.2018.06.165

Caron PJ, Bevan JS, Petersenn S, Flanagan D, Tabarin A, Prevost G et al (2014) Tumor shrinkage with lanreotide Autogel 120 mg as primary therapy in acromegaly: results of a prospective multicenter clinical trial. J Clin Endocrinol Metab 99(4):1282–1290. https://doi.org/10.1210/jc.2013-3318

Petersenn S, Houchard A, Sert C, Caron PJ, Group PS (2020) Predictive factors for responses to primary medical treatment with lanreotide autogel 120 mg in acromegaly: post hoc analyses from the PRIMARYS study. Pituitary 23(2):171–181. https://doi.org/10.1007/s11102-019-01020-3

Bonneville F, Riviere LD, Petersenn S, Bevan J, Houchard A, Sert C et al (2018) MRI T2 signal intensity and tumor response in patients with GH-secreting pituitary macroadenoma: PRIMARYS post-hoc analysis. Eur J Endocrinol 180(3):155–164. https://doi.org/10.1530/EJE-18-0254

Coopmans EC, Korevaar TIM, van Meyel SWF, Daly AF, Chanson P, Brue T et al (2020) Multivariable prediction model for biochemical response to first-generation somatostatin receptor ligands in acromegaly. J Clin Endocrinol Metab 105(9):387. https://doi.org/10.1210/clinem/dgaa387

Neggers SJ, Pronin V, Balcere I, Lee MK, Rozhinskaya L, Bronstein MD et al (2015) Lanreotide Autogel 120 mg at extended dosing intervals in patients with acromegaly biochemically controlled with octreotide LAR: the LEAD study. Eur J Endocrinol 173(3):313–323. https://doi.org/10.1530/EJE-15-0215

Gadelha MR, Bronstein MD, Brue T, Coculescu M, Fleseriu M, Guitelman M et al (2014) Pasireotide versus continued treatment with octreotide or lanreotide in patients with inadequately controlled acromegaly (PAOLA): a randomised, phase 3 trial. Lancet Diabetes Endocrinol 2(11):875–884. https://doi.org/10.1016/S2213-8587(14)70169-X

Colao AAL, Bronstein MD, Brue T, De Marinis L, Fleseriu M, Guitelman M et al (2020) Pasireotide for acromegaly: long-term outcomes from an extension to the Phase III (PAOLA) study. Eur J Endocrinol 182(6):583. https://doi.org/10.1530/EJE-19-0762

Gadelha M, Bex M, Colao A, Pedroza Garcia EM, Poiana C, Jimenez-Sanchez M et al (2019) Evaluation of the efficacy and safety of switching to pasireotide in patients with acromegaly inadequately controlled with first-generation somatostatin analogs. Front Endocrinol (Lausanne) 10:931. https://doi.org/10.3389/fendo.2019.00931

Giustina A, Barkan A, Beckers A, Biermasz N, Biller BMK, Boguszewski C et al (2019) A consensus on the diagnosis and treatment of acromegaly comorbidities: an update. J Clin Endocrinol Metab. 105(4):937–946. https://doi.org/10.1210/clinem/dgz096

Schmid HA, Brue T, Colao A, Gadelha MR, Shimon I, Kapur K et al (2016) Effect of pasireotide on glucose- and growth hormone-related biomarkers in patients with inadequately controlled acromegaly. Endocrine 53(1):210–219. https://doi.org/10.1007/s12020-016-0895-8

Frara S, Maffezzoni F, Mazziotti G, Giustina A (2016) Current and emerging aspects of diabetes mellitus in acromegaly. Trends Endocrinol Metab 27(7):470–483. https://doi.org/10.1016/j.tem.2016.04.014

Colao A, Bronstein MD, Freda P, Gu F, Shen CC, Gadelha M et al (2014) Pasireotide versus octreotide in acromegaly: a head-to-head superiority study. J Clin Endocrinol Metab 99(3):791–799. https://doi.org/10.1210/jc.2013-2480

Shimon I, Adnan Z, Gorshtein A, Baraf L, Saba Khazen N, Gershinsky M et al (2018) Efficacy and safety of long-acting pasireotide in patients with somatostatin-resistant acromegaly: a multicenter study. Endocrine 62(2):448–455. https://doi.org/10.1007/s12020-018-1690-5

Lasolle H, Ferriere A, Vasiljevic A, Eimer S, Nunes ML, Tabarin A (2019) Pasireotide-LAR in acromegaly patients treated with a combination therapy: a real-life study. Endocr Connect 8(10):1383–1394. https://doi.org/10.1530/EC-19-0332

Melmed S (2016) New therapeutic agents for acromegaly. Nat Rev Endocrinol 12(2):90–98. https://doi.org/10.1038/nrendo.2015.196

Samson SL, Nachtigall LB, Fleseriu M, Gordon MB, Ludlam WH, Patou G et al (2020) Results from the phase 3, randomized, double-blind, placebo-controlled CHIASMA OPTIMAL study of oral octreotide capsules in adult patients with acromegaly. J Endocr Soc. https://doi.org/10.1210/jendso/bvaa046.211

Lamberts SWJ, Hofland LJ (2019) ANNIVERSARY REVIEW: Octreotide, 40 years later. Eur J Endocrinol 181(5):R173–R183. https://doi.org/10.1530/EJE-19-0074

Buchfelder M, van der Lely AJ, Biller BMK, Webb SM, Brue T, Strasburger CJ et al (2018) Long-term treatment with pegvisomant: observations from 2090 acromegaly patients in ACROSTUDY. Eur J Endocrinol 179(6):419–427. https://doi.org/10.1530/EJE-18-0616

Tritos NA, Mattsson AF, Vila G, Biller BMK, Klibanski A, Valluri S et al (2020) All-cause mortality in patients with acromegaly treated with pegvisomant: an ACROSTUDY analysis. Eur J Endocrinol 182(3):285–292. https://doi.org/10.1530/EJE-19-0794

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

Boguszewski CL, Huayllas MKP, Vilar L, Naves LA, Ribeiro-Oliveira Junior A, Soares BS et al (2019) Brazilian multicenter study on pegvisomant treatment in acromegaly. Arch Endocrinol Metab 63(4):328–336. https://doi.org/10.20945/2359-3997000000159

Basavilbaso NXG, Ballarino MC, Bruera D, Bruno OD, Chervin AB, Danilowicz K et al (2019) Pegvisomant in acromegaly: a multicenter real-life study in Argentina. Arch Endocrinol Metab 63(4):320–327. https://doi.org/10.20945/2359-3997000000160

Yamaguchi H, Shimatsu A, Okayama A, Sato T (2020) Long-term safety and treatment outcomes of pegvisomant in Japanese patients with acromegaly: results from the post-marketing surveillance. Endocr J 67(2):201–210. https://doi.org/10.1507/endocrj.EJ19-0266

Brue T, Lindberg A, Jan van der Lely A, Akerblad AC, Koltowska-Haggstrom M, Gomez R et al (2019) Diabetes in patients with acromegaly treated with pegvisomant: observations from acrostudy. Endocrine 63(3):563–572. https://doi.org/10.1007/s12020-018-1792-0

Feola T, Cozzolino A, Simonelli I, Sbardella E, Pozza C, Giannetta E et al (2019) Pegvisomant Improves glucose metabolism in acromegaly: a meta-analysis of prospective interventional studies. J Clin Endocrinol Metab 104(7):2892–2902. https://doi.org/10.1210/jc.2018-02281

Ragonese M, Grottoli S, Maffei P, Alibrandi A, Ambrosio MR, Arnaldi G et al (2018) How to improve effectiveness of pegvisomant treatment in acromegalic patients. J Endocrinol Invest 41(5):575–581. https://doi.org/10.1007/s40618-017-0773-0

van der Lely AJ, Jonsson P, 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 175(4):239–245. https://doi.org/10.1530/EJE-16-0008

Strasburger CJ, Mattsson A, Wilton P, Aydin F, Hey-Hadavi J, Biller BMK (2018) Increasing frequency of combination medical therapy in the treatment of acromegaly with the GH receptor antagonist pegvisomant. Eur J Endocrinol 178(4):321–329. https://doi.org/10.1530/EJE-17-0996

Bonert V, Mirocha J, Carmichael J, Yuen KCJ, Araki T, Melmed S (2020) Cost-effectiveness and efficacy of a novel combination regimen in acromegaly: a prospective, randomized trial. J Clin Endocrinol Metab. 105(9):3236–3245. https://doi.org/10.1210/clinem/dgaa444

Muhammad A, van der Lely AJ, Delhanty PJD, Dallenga AHG, Haitsma IK, Janssen J et al (2018) 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 103(2):586–595. https://doi.org/10.1210/jc.2017-02017

Muhammad A, Coopmans EC, Delhanty PJD, Dallenga AHG, Haitsma IK, Janssen J et al (2018) Efficacy and safety of switching to pasireotide in acromegaly patients controlled with pegvisomant and somatostatin analogues: PAPE extension study. Eur J Endocrinol 179(5):269–277. https://doi.org/10.1530/EJE-18-0353

Muhammad A, Coopmans EC, Gatto F, Franck SE, Janssen J, van der Lely AJ et al (2019) Pasireotide responsiveness in acromegaly is mainly driven by somatostatin receptor subtype 2 expression. J Clin Endocrinol Metab 104(3):915–924. https://doi.org/10.1210/jc.2018-01524

Coopmans EC, Schneiders JJ, El-Sayed N, Erler NS, Hofland LJ, van der Lely AJ et al (2020) T2-signal intensity, SSTR expression, and somatostatin analogs efficacy predict response to pasireotide in acromegaly. Eur J Endocrinol 182(6):595–605. https://doi.org/10.1530/EJE-19-0840

Graffeo CS, Donegan D, Erickson D, Brown PD, Perry A, Link MJ et al (2020) The impact of insulin-like growth factor index and biologically effective dose on outcomes after stereotactic radiosurgery for acromegaly: cohort study. Neurosurgery 87(3):538–546. https://doi.org/10.1093/neuros/nyaa054

Knappe UJ, Petroff D, Quinkler M, Schmid SM, Schofl C, Schopohl J et al (2020) Fractionated radiotherapy and radiosurgery in acromegaly: analysis of 352 patients from the German Acromegaly Registry. Eur J Endocrinol 182(3):275–284. https://doi.org/10.1530/EJE-19-0784