ometendoОжирение и метаболизмObesity and metabolism2071-87132306-5524Endocrinology Research Centre10.14341/omet12710ometendo-12710Research ArticleНаучные обзорыReviewsРезистентность к медикаментозному лечению акромегалии и пути ее преодоленияResistance to drug treatment of acromegaly and ways to overcome ithttps://orcid.org/0000-0003-2320-1051ГолоунинаО. О.GolouninaO. O.

Голоунина Ольга Олеговна – студент; eLibrary SPIN: 7793-2123

119991, Москва, ул. Трубецкая, д. 8, стр. 2

Olga O. Golounina, student; eLibrary SPIN: 7793-2123

8-2 Trubetskaya street, 119991 Moscow

olga.golounina@mail.ruhttps://orcid.org/0000-0002-0327-4619ДзерановаЛ. К.DzeranovaL. K.

Дзеранова Лариса Константиновна, доктор медицинских наук; eLibrary SPIN: 2958-5555

Москва

Larisa K. Dzeranova, MD, PhD; eLibrary SPIN: 2958-5555

Moscow

dzeranovalk@yandex.ruhttps://orcid.org/0000-0001-6539-466XПигароваЕ. А.PigarovaE. A.

Пигарова Екатерина Александровна, доктор медицинских наук; eLibrary SPIN: 6912-6331

Москва

Ekaterina A. Pigarova, MD, PhD; eLibrary SPIN: 6912-6331.

Moscow

kpigarova@gmail.comhttps://orcid.org/0000-0002-6674-6441БелаяЖ. Е.BelayaZh. E.

Белая Жанна Евгеньевна, доктор медицинских наук, профессор; eLibrary SPIN: 4746-7173.

Москва

Zhanna E. Belaya, MD, PhD, Professor; eLibrary SPIN: 4746-7173.

Moscow

jannabelaya@gmail.comПервый Московский государственный медицинский университет им. И.М. Сеченова (Сеченовский Университет)РоссияI.M. Sechenov First Moscow State Medical University (Sechenov University)Russian FederationНациональный медицинский исследовательский центр эндокринологииРоссияThe National Medical Research Center for EndocrinologyRussian Federation202124072021182150162Copyright © Голоунина О.О., Дзеранова Л.К., Пигарова Е.А., Белая Ж.Е., 20212021Голоунина О.О., Дзеранова Л.К., Пигарова Е.А., Белая Ж.Е.Golounina O.O., Dzeranova L.K., Pigarova E.A., Belaya Z.E.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://www.omet-endojournals.ru/jour/article/view/12710

Акромегалия — тяжелое инвалидизирующее нейроэндокринное заболевание, обусловленное длительной избыточной продукцией соматотропного гормона и инсулиноподобного фактора роста-1 у лиц с завершенным физиологическим ростом. Проблема резистентности к медикаментозной терапии у пациентов с акромегалией является достаточно распространенной в клинической практике и требует персонализированного подхода с учетом различных клинико-морфологических, молекулярно-генетических и лабораторных предикторов чувствительности к выбору метода лечения. На сегодняшний день аналоги соматостатина первого поколения в большинстве случаев являются препаратами первой линии в медикаментозном лечении акромегалии, однако до 50% пациентов не достигают биохимической ремиссии заболевания. Прогноз чувствительности к аналогам соматостатина имеет огромное значение, а выделение пациентов, у которых данная терапия будет заведомо неуспешной, позволяет сразу предложить альтернативное лечение. В представленном обзоре обобщены потенциальные предикторы чувствительности и резистентности к существующему медикаментозному лечению акромегалии, обсуждаются возможные пути и способы преодоления возникшей резистентности к терапии, предложены варианты персонализированного подхода при выборе лечебной стратегии в отсутствие контроля заболевания на фоне монотерапии аналогами соматостатина, в том числе комбинации «off-label». Своевременное добавление антагониста рецептора гормона роста — пэгвисоманта — позволяет избежать повторного нейрохирургического вмешательства, лучевой терапии или назначения избыточно высоких доз аналогов соматостатина. Оптимальное использование моно- или комбинированной терапии способствует достижению биохимической ремиссии у большинства резистентных к лечению пациентов.

Acromegaly is a severe disabling neuroendocrine disease caused by hypersecretion of growth hormone (GH) and insulin-like growth factor 1 (IGF-1). The problem of resistance to drug therapy in patients with acromegaly is quite common in clinical practice and requires a personalized approach, considering various predictors of sensitivity to the choice of the treatment method. To date, first-generation somatostatin analogues are first-line drugs in the medical treatment of acromegaly, but up to 50% of patients do not achieve biochemical remission of the disease. The prognosis of sensitivity to somatostatin analogues is of great importance and the selection of patients in whom this therapy will be not successful provides invaluable assistance in choosing the optimal treatment approach. This review summarizes potential predictors of sensitivity and resistance to existing drug treatment of acromegaly, discusses possible ways to overcome the resulting resistance to therapy, suggests options for a personalized approach to choosing a treatment strategy in the absence of disease control against the background of monotherapy with somatostatin analogues, including «off-label» combinations. Timely addition of growth hormone receptor antagonist (pegvisomant) avoids repeated neurosurgical intervention, radiation therapy or prescribing excessively high doses of somatostatin analogues. Optimal use of mono- or combination therapy contributes to the achievement of biochemical remission in most resistant patients.

акромегалиябиохимический контрольмедикаментозная терапиярезистентностьаналоги соматостатинапэгвисоманткомбинированная терапияаcromegalybiochemical controlmedical therapyresistancesomatostatin receptor ligandspegvisomantcombined therapyРабота выполнена по инициативе авторов без привлечения финансированияReferencesБелая Ж.Е., Голоунина О.О., Рожинская Л.Я., и др. Эпидемиология, клинические проявления и эффективность различных методов лечения акромегалии по данным единого российского регистра опухолей гипоталамо-гипофизарной области // Проблемы эндокринологии. — 2020. — Т. 66. — №1. — С. 93-103. doi: https://doi.org/10.14341/probl10333.Belaya ZE, Golounina OO, Rozhinskaya LY, et al. Epidemiology, clinical manifestations and efficiency of different methods of treatment of acromegaly according to the United Russian Registry of Patients with Pituitary Tumors. Problems of Endocrinology. 2020;66(1):93-103. (In Russ.). doi: https://doi.org/10.14341/probl10333.Dal J, Feldt-Rasmussen U, Andersen M, et al. Acromegaly incidence, prevalence, complications and long-term prognosis: a nationwide cohort study. European Journal of Endocrinology. 2016;175(3):181-190. doi: https://doi.org/10.1530/EJE-16-0117Dal J, Feldt-Rasmussen U, Andersen M, et al. Acromegaly incidence, prevalence, complications and long-term prognosis: a nationwide cohort study. European Journal of Endocrinology. 2016;175(3):181-190. doi: https://doi.org/10.1530/EJE-16-0117Gatto F, Trifirò G, Lapi F, et al. Epidemiology of acromegaly in Italy: analysis from a large longitudinal primary care database. Endocrine. 2018;61(3):533-541. doi: https://doi.org/10.1007/s12020-018-1630-4Gatto F, Trifirò G, Lapi F, et al. Epidemiology of acromegaly in Italy: analysis from a large longitudinal primary care database. Endocrine. 2018;61(3):533-541. doi: https://doi.org/10.1007/s12020-018-1630-4Lavrentaki A, Paluzzi A, Wass JAH, Karavitaki N. Epidemiology of acromegaly: review of population studies. Pituitary. 2017;20(1):4-9. doi: https://doi.org/10.1007/s11102-016-0754-xLavrentaki A, Paluzzi A, Wass JAH, Karavitaki N. Epidemiology of acromegaly: review of population studies. Pituitary. 2017;20(1):4-9. doi: https://doi.org/10.1007/s11102-016-0754-xKasuki L, Antunes X, Lamback EB, Gadelha MR. Acromegaly: Update on Management and Long-Term Morbidities. Endocrinol Metab Clin North Am. 2020;49(3):475-486. doi: https://doi.org/10.1016/j.ecl.2020.05.007Kasuki L, Antunes X, Lamback EB, Gadelha MR. Acromegaly: Update on Management and Long-Term Morbidities. Endocrinol Metab Clin North Am. 2020;49(3):475-486. doi: https://doi.org/10.1016/j.ecl.2020.05.007Дедов И.И., Молитвословова Н.Н., Рожинская Л.Я., Мельниченко Г.А. Федеральные клинические рекомендации по клинике, диагностике, дифференциальной диагностике и методам лечения акромегалии // Проблемы эндокринологии. — 2013. — Т. 59. — №6. — С. 4-18. doi: https://doi.org/10.14341/probl20135964-18Dedov II, Molitvoslovova NN, Rozhinskaia LI, Melnichenko GA. Russian Association of Endocrinologists National Practice Guidelines (clinical signs, diagnosis, differential diagnosis, treatment). Acromegaly. Problems of Endocrinology. 2013;59(6):4-18. (In Russ.). doi: https://doi.org/10.14341/probl20135964-18Melmed S, Bronstein MD, Chanson P, et al. A Consensus Statement on acromegaly therapeutic outcomes. Nat Rev Endocrinol. 2018;14(9):552-561. doi: https://doi.org/10.1038/s41574-018-0058-5Melmed S, Bronstein MD, Chanson P, et al. A Consensus Statement on acromegaly therapeutic outcomes. Nat Rev Endocrinol. 2018;14(9):552-561. doi: https://doi.org/10.1038/s41574-018-0058-5Babu H, Ortega A, Nuno M, et al. Long-Term Endocrine Outcomes Following Endoscopic Endonasal Transsphenoidal Surgery for Acromegaly and Associated Prognostic Factors. Neurosurgery. 2017;81(2):357-366. doi: https://doi.org/10.1093/neuros/nyx020Babu H, Ortega A, Nuno M, et al. Long-Term Endocrine Outcomes Following Endoscopic Endonasal Transsphenoidal Surgery for Acromegaly and Associated Prognostic Factors. Neurosurgery. 2017;81(2):357-366. doi: https://doi.org/10.1093/neuros/nyx020Anik I, Cabuk B, Gokbel A, et al. Endoscopic Transsphenoidal Approach for Acromegaly with Remission Rates in 401 Patients: 2010 Consensus Criteria. World Neurosurgery. 2017;108:278-290. doi: https://doi.org/10.1016/j.wneu.2017.08.182Anik I, Cabuk B, Gokbel A, et al. Endoscopic Transsphenoidal Approach for Acromegaly with Remission Rates in 401 Patients: 2010 Consensus Criteria. World Neurosurgery. 2017;108:278-290. doi: https://doi.org/10.1016/j.wneu.2017.08.182Mortini P, Barzaghi LR, Albano L, et al. Microsurgical therapy of pituitary adenomas. Endocrine. 2018;59(1):72-81. doi: https://doi.org/10.1007/s12020-017-1458-3Mortini P, Barzaghi LR, Albano L, et al. Microsurgical therapy of pituitary adenomas. Endocrine. 2018;59(1):72-81. doi: https://doi.org/10.1007/s12020-017-1458-3Maione L, Chanson P. National acromegaly registries. Best Practice & Research Clinical Endocrinology & Metabolism 2019;33(2):101264. doi: https://doi.org/10.1016/j.beem.2019.02.001Maione L, Chanson P. National acromegaly registries. Best Practice & Research Clinical Endocrinology & Metabolism 2019;33(2):101264. doi: https://doi.org/10.1016/j.beem.2019.02.001Ding D, Mehta GU, Patibandla MR, et al. Stereotactic Radiosurgery for Acromegaly: An International Multicenter Retrospective Cohort Study. Neurosurgery. 2019;84(3):717-725. doi: https://doi.org/10.1093/neuros/nyy178Ding D, Mehta GU, Patibandla MR, et al. Stereotactic Radiosurgery for Acromegaly: An International Multicenter Retrospective Cohort Study. Neurosurgery. 2019;84(3):717-725. doi: https://doi.org/10.1093/neuros/nyy178Abu Dabrh AM, Asi N, Farah WH, et al. Radiotherapy versus radiosurgery in treating patients with acromegaly: a systematic review and meta-analysis. Endocrine Practice. 2015;21(8):943-956. doi: https://doi.org/10.4158/EP14574.ORAbu Dabrh AM, Asi N, Farah WH, et al. Radiotherapy versus radiosurgery in treating patients with acromegaly: a systematic review and meta-analysis. Endocrine Practice. 2015;21(8):943-956. doi: https://doi.org/10.4158/EP14574.ORChanson P, Brue T, Delemer B, et al. Pegvisomant treatment in patients with acromegaly in clinical practice: The French ACROSTUDY. Annales d’Endocrinologie 2015;76(6):664-670. doi: https://doi.org/10.1016/j.ando.2015.10.003Chanson P, Brue T, Delemer B, et al. Pegvisomant treatment in patients with acromegaly in clinical practice: The French ACROSTUDY. Annales d’Endocrinologie 2015;76(6):664-670. doi: https://doi.org/10.1016/j.ando.2015.10.003Burness CB, Dhillon S, Keam SJ. Lanreotide autogel(®): a review of its use in the treatment of patients with acromegaly. Drugs. 2014;74(14):1673-1691. doi: https://doi.org/10.1007/s40265-014-0283-8Burness CB, Dhillon S, Keam SJ. Lanreotide autogel(®): a review of its use in the treatment of patients with acromegaly. Drugs. 2014;74(14):1673-1691. doi: https://doi.org/10.1007/s40265-014-0283-8Paragliola RM, Salvatori R. Novel Somatostatin Receptor Ligands Therapies for Acromegaly. Front Endocrinol (Lausanne). 2018;9:78. doi: https://doi.org/10.3389/fendo.2018.00078Paragliola RM, Salvatori R. Novel Somatostatin Receptor Ligands Therapies for Acromegaly. Front Endocrinol (Lausanne). 2018;9:78. doi: https://doi.org/10.3389/fendo.2018.00078Marina D, Burman P, Klose M, et al. Truncated somatostatin receptor 5 may modulate therapy response to somatostatin analogues — Observations in two patients with acromegaly and severe headache. Growth Horm IGF Res. 2015;25(5):262-267. doi: https://doi.org/10.1016/j.ghir.2015.07.003Marina D, Burman P, Klose M, et al. Truncated somatostatin receptor 5 may modulate therapy response to somatostatin analogues — Observations in two patients with acromegaly and severe headache. Growth Horm IGF Res. 2015;25(5):262-267. doi: https://doi.org/10.1016/j.ghir.2015.07.003Freda PU, Katznelson L, van der Lely AJ, et al. Long-acting somatostatin analog therapy of acromegaly: a meta-analysis. J Clin Endocrinol Metab. 2005;90(8):4465-4473. doi: https://doi.org/10.1210/jc.2005-0260Freda PU, Katznelson L, van der Lely AJ, et al. Long-acting somatostatin analog therapy of acromegaly: a meta-analysis. J Clin Endocrinol Metab. 2005;90(8):4465-4473. doi: https://doi.org/10.1210/jc.2005-0260Espinosa-de-los-Monteros AL, Gonzalez B, Vargas G, et al. Octreotide LAR treatment of acromegaly in «real life»: long-term outcome at a tertiary care center. Pituitary. 2015;18(3):290-296. doi: https://doi.org/10.1007/s11102-014-0570-0Espinosa-de-los-Monteros AL, Gonzalez B, Vargas G, et al. Octreotide LAR treatment of acromegaly in «real life»: long-term outcome at a tertiary care center. Pituitary. 2015;18(3):290-296. doi: https://doi.org/10.1007/s11102-014-0570-0Shimatsu A, Teramoto A, Hizuka N, et al. Efficacy, safety, and pharmacokinetics of sustained-release lanreotide (lanreotide Autogel) in Japanese patients with acromegaly or pituitary gigantism. Endocr J. 2013;60(5):651-663. doi: 10.1507/endocrj.ej12-0417Shimatsu A, Teramoto A, Hizuka N, et al. Efficacy, safety, and pharmacokinetics of sustained-release lanreotide (lanreotide Autogel) in Japanese patients with acromegaly or pituitary gigantism. Endocr J. 2013;60(5):651-663. doi: 10.1507/endocrj.ej12-0417Древаль А.В., Покрамович Ю.Г., Тишенина Р.С. Эффективность аналога соматостатина длительного действия октреотида-депо в лечении больных с активной фазой акромегалии // Проблемы эндокринологии. — 2014. — T. 46. — №3. — C. 10-14. doi: https://doi.org/10.14341/probl201460310-14Dreval AV, Pokramovich YG, Tishenina RS. The effectiveness of octreotide-depo, a long-acting somatostatin analog for the treatment of the patients with active phase of acromegalia. Problems of Endocrinology. 2014;46(3):10-14. (In Russ.). doi: https://doi.org/10.14341/probl201460310-14Gatto F, Campana C, Cocchiara F, et al. Current perspectives on the impact of clinical disease and biochemical control on comorbidities and quality of life in acromegaly. Rev Endocr Metab Disord. 2019;20(3):365-381. doi: https://doi.org/10.1007/s11154-019-09506-yGatto F, Campana C, Cocchiara F, et al. Current perspectives on the impact of clinical disease and biochemical control on comorbidities and quality of life in acromegaly. Rev Endocr Metab Disord. 2019;20(3):365-381. doi: https://doi.org/10.1007/s11154-019-09506-yTheodoropoulou M, Stalla GK. Somatostatin receptors: From signaling to clinical practice. Frontiers in Neuroendocrinology. 2013;34(3):228-252. doi: https://doi.org/10.1016/j.yfrne.2013.07.005Theodoropoulou M, Stalla GK. Somatostatin receptors: From signaling to clinical practice. Frontiers in Neuroendocrinology. 2013;34(3):228-252. doi: https://doi.org/10.1016/j.yfrne.2013.07.005Kurosaki M, Saegert W, Abe T, Lüdecke DK. Expression of vascular endothelial growth factor in growth hormone-secreting pituitary adenomas: special reference to the octreotide treatment. Neurol Res. 2008;30(5):518-522. doi: https://doi.org/10.1179/174313208X289499Kurosaki M, Saegert W, Abe T, Lüdecke DK. Expression of vascular endothelial growth factor in growth hormone-secreting pituitary adenomas: special reference to the octreotide treatment. Neurol Res. 2008;30(5):518-522. doi: https://doi.org/10.1179/174313208X289499Giustina A, Mazziotti G, Torri V, et al. Meta-analysis on the effects of octreotide on tumor mass in acromegaly. PLoS One. 2012;7(5):e36411. doi: https://doi.org/10.1371/journal.pone.0036411Giustina A, Mazziotti G, Torri V, et al. Meta-analysis on the effects of octreotide on tumor mass in acromegaly. PLoS One. 2012;7(5):e36411. doi: https://doi.org/10.1371/journal.pone.0036411Colao A, Auriemma RS, Pivonello R. The effects of somatostatin analogue therapy on pituitary tumor volume in patients with acromegaly. Pituitary 2016;19(2):210-221. doi: https://doi.org/10.1007/s11102-015-0677-yColao A, Auriemma RS, Pivonello R. The effects of somatostatin analogue therapy on pituitary tumor volume in patients with acromegaly. Pituitary 2016;19(2):210-221. doi: https://doi.org/10.1007/s11102-015-0677-yColao A, Auriemma RS, Lombardi G, Pivonello R. Resistance to somatostatin analogs in acromegaly. Endocr Rev. 2011;32(2):247-271. doi: https://doi.org/10.1210/er.2010-0002Colao A, Auriemma RS, Lombardi G, Pivonello R. Resistance to somatostatin analogs in acromegaly. Endocr Rev. 2011;32(2):247-271. doi: https://doi.org/10.1210/er.2010-0002Besser GM, Burman P, Daly AF. Predictors and rates of treatment-resistant tumor growth in acromegaly. Eur J Endocrinol. 2005;153(2):187-193. doi: https://doi.org/10.1530/eje.1.01968Besser GM, Burman P, Daly AF. Predictors and rates of treatment-resistant tumor growth in acromegaly. Eur J Endocrinol. 2005;153(2):187-193. doi: https://doi.org/10.1530/eje.1.01968Casarini APM, Pinto EM, Jallad RS, et al. Dissociation between tumor shrinkage and hormonal response during somatostatin analog treatment in an acromegalic patient: Preferential expression of somatostatin receptor subtype 3. J Endocrinol Invest. 2006;29(9):826-830. doi: https://doi.org/10.1007/BF03347378Casarini APM, Pinto EM, Jallad RS, et al. Dissociation between tumor shrinkage and hormonal response during somatostatin analog treatment in an acromegalic patient: Preferential expression of somatostatin receptor subtype 3. J Endocrinol Invest. 2006;29(9):826-830. doi: https://doi.org/10.1007/BF03347378Cuevas-Ramos D, Fleseriu M. Somatostatin receptor ligands and resistance to treatment in pituitary adenomas. Journal of Molecular Endocrinology 2014;52(3):223-240. doi: https://doi.org/10.1530/JME-14-0011Cuevas-Ramos D, Fleseriu M. Somatostatin receptor ligands and resistance to treatment in pituitary adenomas. Journal of Molecular Endocrinology 2014;52(3):223-240. doi: https://doi.org/10.1530/JME-14-0011Gatto F, Biermasz NR, Feelders RA, et al. Low beta-arrestin expression correlates with the responsiveness to long-term somatostatin analog treatment in acromegaly. European Journal of Endocrinology. 2016;174(5):651-662. doi: https://doi.org/10.1530/EJE-15-0391Gatto F, Biermasz NR, Feelders RA, et al. Low beta-arrestin expression correlates with the responsiveness to long-term somatostatin analog treatment in acromegaly. European Journal of Endocrinology. 2016;174(5):651-662. doi: https://doi.org/10.1530/EJE-15-0391Remes SM, Leijon HL, Vesterinen TJ, et al. Immunohistochemical expression of somatostatin receptor subtypes in a panel of neuroendocrine neoplasias. J Histochem Cytochem 2019;67(10):735-743. doi: https://doi.org/10.1369/0022155419856900Remes SM, Leijon HL, Vesterinen TJ, et al. Immunohistochemical expression of somatostatin receptor subtypes in a panel of neuroendocrine neoplasias. J Histochem Cytochem 2019;67(10):735-743. doi: https://doi.org/10.1369/0022155419856900Tulipano G, Bonfanti C, Milani G, et al. Differential Inhibition of Growth Hormone Secretion by Analogs Selective for Somatostatin Receptor Subtypes 2 and 5 in Human Growth-Hormone-Secreting Adenoma Cells in vitro. Neuroendocrinology. 2001;73(5):344-351. doi: https://doi.org/10.1159/000054651Tulipano G, Bonfanti C, Milani G, et al. Differential Inhibition of Growth Hormone Secretion by Analogs Selective for Somatostatin Receptor Subtypes 2 and 5 in Human Growth-Hormone-Secreting Adenoma Cells in vitro. Neuroendocrinology. 2001;73(5):344-351. doi: https://doi.org/10.1159/000054651Hofland LJ, Lamberts SWJ. The Pathophysiological Consequences of Somatostatin Receptor Internalization and Resistance. Endocrine Reviews. 2003;24(1):28-47. doi: https://doi.org/10.1210/er.2000-0001Hofland LJ, Lamberts SWJ. The Pathophysiological Consequences of Somatostatin Receptor Internalization and Resistance. Endocrine Reviews. 2003;24(1):28-47. doi: https://doi.org/10.1210/er.2000-0001Gadelha MR, Wildemberg LE, Bronstein MD, et al. Somatostatin receptor ligands in the treatment of acromegaly. Pituitary 2017;20(1):100-108. doi: https://doi.org/10.1007/s11102-017-0791-0Gadelha MR, Wildemberg LE, Bronstein MD, et al. Somatostatin receptor ligands in the treatment of acromegaly. Pituitary 2017;20(1):100-108. doi: https://doi.org/10.1007/s11102-017-0791-0Chinezu L, Vasiljevic A, Jouanneau E, et al. Expression of somatostatin receptors, SSTR2A and SSTR5, in 108 endocrine pituitary tumors using immunohistochemical detection with new specific monoclonal antibodies. Human Pathology. 2014;45(1):71-77. doi: https://doi.org/10.1016/j.humpath.2013.08.007Chinezu L, Vasiljevic A, Jouanneau E, et al. Expression of somatostatin receptors, SSTR2A and SSTR5, in 108 endocrine pituitary tumors using immunohistochemical detection with new specific monoclonal antibodies. Human Pathology. 2014;45(1):71-77. doi: https://doi.org/10.1016/j.humpath.2013.08.007Iacovazzo D, Carlsen E, Lugli F, et al. Factors predicting pasireotide responsiveness in somatotroph pituitary adenomas resistant to first-generation somatostatin analogues: an immunohistochemical study. Eur J Endocrinol. 2016;174(2):241-250. doi: https://doi.org/10.1530/EJE-15-0832Iacovazzo D, Carlsen E, Lugli F, et al. Factors predicting pasireotide responsiveness in somatotroph pituitary adenomas resistant to first-generation somatostatin analogues: an immunohistochemical study. Eur J Endocrinol. 2016;174(2):241-250. doi: https://doi.org/10.1530/EJE-15-0832Venegas-Moreno E, Vazquez-Borrego MC, Dios E, et al. Association between dopamine and somatostatin receptor expression and pharmacological response to somatostatin analogues in acromegaly. J Cell Mol Med. 2018;22(3):1640-1649. doi: https://doi.org/10.1111/jcmm.13440Venegas-Moreno E, Vazquez-Borrego MC, Dios E, et al. Association between dopamine and somatostatin receptor expression and pharmacological response to somatostatin analogues in acromegaly. J Cell Mol Med. 2018;22(3):1640-1649. doi: https://doi.org/10.1111/jcmm.13440Paragliola RM, Corsello SM, Salvatori R. Somatostatin receptor ligands in acromegaly: clinical response and factors predicting resistance. Pituitary. 2017;20(1):109-115. doi: https://doi.org/10.1007/s11102-016-0768-4Paragliola RM, Corsello SM, Salvatori R. Somatostatin receptor ligands in acromegaly: clinical response and factors predicting resistance. Pituitary. 2017;20(1):109-115. doi: https://doi.org/10.1007/s11102-016-0768-4Ramos-Leví AM, Bernabeu I, Sampedro-Núñez M, Marazuela M. Genetic Predictors of Response to Different Medical Therapies in Acromegaly. Prog Mol Biol Transl Sci. 2016;138:85-114. doi: https://doi.org/10.1016/bs.pmbts.2015.10.016Ramos-Leví AM, Bernabeu I, Sampedro-Núñez M, Marazuela M. Genetic Predictors of Response to Different Medical Therapies in Acromegaly. Prog Mol Biol Transl Sci. 2016;138:85-114. doi: https://doi.org/10.1016/bs.pmbts.2015.10.016Taboada GF, Luque RM, Neto LV, et al. Quantitative analysis of somatostatin receptor subtypes (1–5) gene expression levels in somatotropinomas and correlation to in vivo hormonal and tumor volume responses to treatment with octreotide LAR. European Journal of Endocrinology. 2008;158(3):295-303. doi: https://doi.org/10.1530/EJE-07-0562Taboada GF, Luque RM, Neto LV, et al. Quantitative analysis of somatostatin receptor subtypes (1–5) gene expression levels in somatotropinomas and correlation to in vivo hormonal and tumor volume responses to treatment with octreotide LAR. European Journal of Endocrinology. 2008;158(3):295-303. doi: https://doi.org/10.1530/EJE-07-0562Fougner SL, Casar-Borota O, Heck A, et al. Adenoma granulation pattern correlates with clinical variables and effect of somatostatin analogue treatment in a large series of patients with acromegaly: Granulation in somatotroph adenomas. Clinical Endocrinology 2012;76(1):96-102. doi: https://doi.org/10.1111/j.1365-2265.2011.04163.xFougner SL, Casar-Borota O, Heck A, et al. Adenoma granulation pattern correlates with clinical variables and effect of somatostatin analogue treatment in a large series of patients with acromegaly: Granulation in somatotroph adenomas. Clinical Endocrinology 2012;76(1):96-102. doi: https://doi.org/10.1111/j.1365-2265.2011.04163.xGil J, Marqués-Pamies M, Jordà M, et al. Molecular determinants of enhanced response to somatostatin receptor ligands after debulking in large GH producing adenomas. Clin Endocrinol (Oxf) 2020. doi: https://doi.org/10.1111/cen.14339.Gil J, Marqués-Pamies M, Jordà M, et al. Molecular determinants of enhanced response to somatostatin receptor ligands after debulking in large GH producing adenomas. Clin Endocrinol (Oxf) 2020. doi: https://doi.org/10.1111/cen.14339.Kasuki L, Wildemberg LEA, Neto LV, et al. Ki-67 is a predictor of acromegaly control with octreotide LAR independent of SSTR2 status and relates to cytokeratin pattern. European Journal of Endocrinology. 2013;169(2):217-223. doi: https://doi.org/10.1530/EJE-13-0349Kasuki L, Wildemberg LEA, Neto LV, et al. Ki-67 is a predictor of acromegaly control with octreotide LAR independent of SSTR2 status and relates to cytokeratin pattern. European Journal of Endocrinology. 2013;169(2):217-223. doi: https://doi.org/10.1530/EJE-13-0349Larkin S, Reddy R, Karavitaki N, et al. Granulation pattern, but not GSP or GHR mutation, is associated with clinical characteristics in somatostatin-naive patients with somatotroph adenomas. Eur J Endocrinol. 2013;168(4):491-499. doi: https://doi.org/10.1530/EJE-12-0864Larkin S, Reddy R, Karavitaki N, et al. Granulation pattern, but not GSP or GHR mutation, is associated with clinical characteristics in somatostatin-naive patients with somatotroph adenomas. Eur J Endocrinol. 2013;168(4):491-499. doi: https://doi.org/10.1530/EJE-12-0864Sherlock M, Fernandez-Rodriguez E, Alonso AA, et al. Medical therapy in patients with acromegaly: predictors of response and comparison of efficacy of dopamine agonists and somatostatin analogues. J Clin Endocrinol Metab. 2009;94(4):1255-1263. doi: https://doi.org/10.1210/jc.2008-1420Sherlock M, Fernandez-Rodriguez E, Alonso AA, et al. Medical therapy in patients with acromegaly: predictors of response and comparison of efficacy of dopamine agonists and somatostatin analogues. J Clin Endocrinol Metab. 2009;94(4):1255-1263. doi: https://doi.org/10.1210/jc.2008-1420Пржиялковская Е.Г., Османова П.О., Мамедова Е.О., и др. Предиктивные биомаркеры в лечении акромегалии: обзор литературы // Вестник РАМН. — 2019. — Т. 74. — №6. — С. 430-440. doi: https://doi.org/10.15690/vramn1181Przhiyalkovskaya EG, Osmanova PO, Mamedova EO, et al. Predictive biomarkers in the treatment of acromegaly: a review of the literature. Annals RAMS. 2019;74(6):430-440. (In Russ.). doi: https://doi.org/10.15690/vramn1181Bilbao Garay I, Daly AF, Egaña Zunzunegi N, Beckers A. Pituitary Disease in AIP Mutation-Positive Familial Isolated Pituitary Adenoma (FIPA): A Kindred-Based Overview. J Clin Med. 2020;9(6):2003. doi: https://doi.org/10.3390/jcm9062003Bilbao Garay I, Daly AF, Egaña Zunzunegi N, Beckers A. Pituitary Disease in AIP Mutation-Positive Familial Isolated Pituitary Adenoma (FIPA): A Kindred-Based Overview. J Clin Med. 2020;9(6):2003. doi: https://doi.org/10.3390/jcm9062003Hannah-Shmouni F, Trivellin G, Stratakis CA. Genetics of gigantism and acromegaly. Growth Horm IGF Res. 2016;30-31:37-41. doi: https://doi.org/10.1016/j.ghir.2016.08.002Hannah-Shmouni F, Trivellin G, Stratakis CA. Genetics of gigantism and acromegaly. Growth Horm IGF Res. 2016;30-31:37-41. doi: https://doi.org/10.1016/j.ghir.2016.08.002Daly AF, Beckers A. Familial isolated pituitary adenomas (FIPA) and mutations in the aryl hydrocarbon receptor interacting protein (AIP) gene. Endocrinol Metab Clin North Am. 2015;44(1):19-25. doi: https://doi.org/10.1016/j.ecl.2014.10.002Daly AF, Beckers A. Familial isolated pituitary adenomas (FIPA) and mutations in the aryl hydrocarbon receptor interacting protein (AIP) gene. Endocrinol Metab Clin North Am. 2015;44(1):19-25. doi: https://doi.org/10.1016/j.ecl.2014.10.002Мамедова Е.О., Пржиялковская Е.Г., Пигарова Е.А., и др. Аденомы гипофиза в рамках наследственных синдромов // Проблемы эндокринологии. — 2014. — Т. 60. — №4. — С. 51-59. doi: https://doi.org/10.14341/probl201460438-46Mamedova EO, Przhiyalkovskaya EG, Pigarova EA, et al. Pituitary adenomas in the framework of hereditary syndromes. Probl Endocrinol. 2014;60(4):51-59. (In Russ.). doi: https://doi.org/10.14341/probl201460438-46Tuominen I, Heliövaara E, Raitila A, et al. AIP inactivation leads to pituitary tumorigenesis through defective Gαi-cAMP signaling. Oncogene. 2015;34(9):1174-1184. doi: https://doi.org/10.1038/onc.2014.50Tuominen I, Heliövaara E, Raitila A, et al. AIP inactivation leads to pituitary tumorigenesis through defective Gαi-cAMP signaling. Oncogene. 2015;34(9):1174-1184. doi: https://doi.org/10.1038/onc.2014.50Theodoropoulou M, Stalla GK, Spengler D. ZAC1 target genes and pituitary tumorigenesis. Molecular and Cellular Endocrinology 2010;326(1-2):60-65. doi: https://doi.org/10.1016/j.mce.2010.01.033Theodoropoulou M, Stalla GK, Spengler D. ZAC1 target genes and pituitary tumorigenesis. Molecular and Cellular Endocrinology 2010;326(1-2):60-65. doi: https://doi.org/10.1016/j.mce.2010.01.033Venegas-Moreno E, Flores-Martinez A, Dios E, et al. E-cadherin expression is associated with somatostatin analogue response in acromegaly. J Cell Mol Med. 2019;23(5):3088-3096. doi: https://doi.org/10.1111/jcmm.13851Venegas-Moreno E, Flores-Martinez A, Dios E, et al. E-cadherin expression is associated with somatostatin analogue response in acromegaly. J Cell Mol Med. 2019;23(5):3088-3096. doi: https://doi.org/10.1111/jcmm.13851Potorac I, Petrossians P, Daly AF, et al. T2-weighted MRI signal predicts hormone and tumor responses to somatostatin analogs in acromegaly. Endocrine-Related Cancer. 2016;23(11):871-881. doi: https://doi.org/10.1530/ERC-16-0356Potorac I, Petrossians P, Daly AF, et al. T2-weighted MRI signal predicts hormone and tumor responses to somatostatin analogs in acromegaly. Endocrine-Related Cancer. 2016;23(11):871-881. doi: https://doi.org/10.1530/ERC-16-0356Пронин В.С. Диагностические и прогностические факторы, определяющие особенности клинического течения и тактику лечения акромегалии: Дис. … докт. мед. наук. — Москва; 2011.Pronin VS. Diagnosticheskie i prognosticheskie faktory, opredelyayushchie osobennosti klinicheskogo techeniya i taktiku lecheniya akromegalii. [dissertation] Moscow; 2011. (In Russ.)].Colao A, Pivonello R, Auriemma RS, et al. Beneficial effect of dose escalation of octreotide-LAR as first-line therapy in patients with acromegaly. Eur J Endocrinol. 2007;157(5):579-587. doi: https://doi.org/10.1530/EJE-07-0383Colao A, Pivonello R, Auriemma RS, et al. Beneficial effect of dose escalation of octreotide-LAR as first-line therapy in patients with acromegaly. Eur J Endocrinol. 2007;157(5):579-587. doi: https://doi.org/10.1530/EJE-07-0383Giustina A, Bonadonna S, Bugari G, et al. High-dose intramuscular octreotide in patients with acromegaly inadequately controlled on conventional somatostatin analogue therapy: a randomised controlled trial. Eur J Endocrinol. 2009;161(2):331-338. doi: https://doi.org/10.1530/EJE-09-0372Giustina A, Bonadonna S, Bugari G, et al. High-dose intramuscular octreotide in patients with acromegaly inadequately controlled on conventional somatostatin analogue therapy: a randomised controlled trial. Eur J Endocrinol. 2009;161(2):331-338. doi: https://doi.org/10.1530/EJE-09-0372Giustina A, Mazziotti G, Cannavò S, et al. High-Dose and High-Frequency Lanreotide Autogel in Acromegaly: A Randomized, Multicenter Study. J Clin Endocrinol Metab. 2017;102(7):2454-2464. doi: https://doi.org/10.1210/jc.2017-00142Giustina A, Mazziotti G, Cannavò S, et al. High-Dose and High-Frequency Lanreotide Autogel in Acromegaly: A Randomized, Multicenter Study. J Clin Endocrinol Metab. 2017;102(7):2454-2464. doi: https://doi.org/10.1210/jc.2017-00142Grasso LFS, Auriemma RS, Pivonello R, Colao A. Somatostatin analogs, cabergoline and pegvisomant: comparing the efficacy of medical treatment for acromegaly. Expert Review of Endocrinology & Metabolism. 2017;12(1):73-85. doi: https://doi.org/10.1080/17446651.2016.1222899Grasso LFS, Auriemma RS, Pivonello R, Colao A. Somatostatin analogs, cabergoline and pegvisomant: comparing the efficacy of medical treatment for acromegaly. Expert Review of Endocrinology & Metabolism. 2017;12(1):73-85. doi: https://doi.org/10.1080/17446651.2016.1222899Gatto F, Arvigo M, Amarù J, et al. Cell specific interaction of pasireotide: review of preclinical studies in somatotroph and corticotroph pituitary cells. Pituitary. 2019;22(1):89-99. doi: https://doi.org/10.1007/s11102-018-0926-yGatto F, Arvigo M, Amarù J, et al. Cell specific interaction of pasireotide: review of preclinical studies in somatotroph and corticotroph pituitary cells. Pituitary. 2019;22(1):89-99. doi: https://doi.org/10.1007/s11102-018-0926-yColao A, Bronstein MD, Freda P, al. Pasireotide versus octreotide in acromegaly: a head-to-head superiority study. J Clin Endocrinol Metab. 2014;99(3):791-799. doi: https://doi.org/10.1210/jc.2013-2480Colao A, Bronstein MD, Freda P, al. Pasireotide versus octreotide in acromegaly: a head-to-head superiority study. J Clin Endocrinol Metab. 2014;99(3):791-799. doi: https://doi.org/10.1210/jc.2013-2480Gadelha MR, Bronstein MD, Brue T, et al. Pasireotide versus continued treatment with octreotide or lanreotide in patients with inadequately controlled acromegaly (PAOLA): a randomised, phase 3 trial. Lancet Diabetes Endocrinol. 2014;2(11):875-884. doi: https://doi.org/10.1016/S2213-8587(14)70169-XGadelha MR, Bronstein MD, Brue T, et al. Pasireotide versus continued treatment with octreotide or lanreotide in patients with inadequately controlled acromegaly (PAOLA): a randomised, phase 3 trial. Lancet Diabetes Endocrinol. 2014;2(11):875-884. doi: https://doi.org/10.1016/S2213-8587(14)70169-XShimon I, Adnan Z, Gorshtein A, et al. Efficacy and safety of long-acting pasireotide in patients with somatostatin-resistant acromegaly: a multicenter study. Endocrine. 2018;62(2):448-455. doi: https://doi.org/10.1007/s12020-018-1690-5Shimon I, Adnan Z, Gorshtein A, et al. Efficacy and safety of long-acting pasireotide in patients with somatostatin-resistant acromegaly: a multicenter study. Endocrine. 2018;62(2):448-455. doi: https://doi.org/10.1007/s12020-018-1690-5Chanson P. Medical Treatment of Acromegaly with Dopamine Agonists or Somatostatin Analogs. Neuroendocrinology. 2016;103(1):50-58. doi: https://doi.org/10.1159/000377704Chanson P. Medical Treatment of Acromegaly with Dopamine Agonists or Somatostatin Analogs. Neuroendocrinology. 2016;103(1):50-58. doi: https://doi.org/10.1159/000377704Kuhn E, Chanson P. Cabergoline in acromegaly. Pituitary. 2017;20(1):121-128. doi: https://doi.org/10.1007/s11102-016-0782-6Kuhn E, Chanson P. Cabergoline in acromegaly. Pituitary. 2017;20(1):121-128. doi: https://doi.org/10.1007/s11102-016-0782-6Sandret L, Maison P, Chanson P. Place of cabergoline in acromegaly: a meta-analysis. J Clin Endocrinol Metab. 2011;96(5):1327-1335. doi: https://doi.org/10.1210/jc.2010-2443Sandret L, Maison P, Chanson P. Place of cabergoline in acromegaly: a meta-analysis. J Clin Endocrinol Metab. 2011;96(5):1327-1335. doi: https://doi.org/10.1210/jc.2010-2443Giraldi EA, Ioachimescu AG. The Role of Dopamine Agonists in Pituitary Adenomas. Endocrinol Metab Clin North Am. 2020;49(3):453-474. doi: https://doi.org/10.1016/j.ecl.2020.05.006Giraldi EA, Ioachimescu AG. The Role of Dopamine Agonists in Pituitary Adenomas. Endocrinol Metab Clin North Am. 2020;49(3):453-474. doi: https://doi.org/10.1016/j.ecl.2020.05.006Sahin S, Fidan MC, Korkmaz OP, et al. Effectiveness of Cabergoline Treatment in Patients with Acromegaly Uncontrolled with SSAs: Experience of a Single Tertiary Center. Exp Clin Endocrinol Diabetes. 2020:1274-1276. doi: https://doi.org/10.1055/a-1274-1276Sahin S, Fidan MC, Korkmaz OP, et al. Effectiveness of Cabergoline Treatment in Patients with Acromegaly Uncontrolled with SSAs: Experience of a Single Tertiary Center. Exp Clin Endocrinol Diabetes. 2020:1274-1276. doi: https://doi.org/10.1055/a-1274-1276Kopchick JJ, Parkinson C, Stevens EC, Trainer PJ. Growth hormone receptor antagonists: discovery, development, and use in patients with acromegaly. Endocr Rev. 2002;23(5):623-646. doi: https://doi.org/10.1210/er.2001-0022Kopchick JJ, Parkinson C, Stevens EC, Trainer PJ. Growth hormone receptor antagonists: discovery, development, and use in patients with acromegaly. Endocr Rev. 2002;23(5):623-646. doi: https://doi.org/10.1210/er.2001-0022Higham CE, Chung TT, Lawrance J, et al. Long-term experience of pegvisomant therapy as a treatment for acromegaly. Clinical Endocrinology. 2009;71(1):86-91. doi: https://doi.org/10.1111/j.1365-2265.2008.03469.xHigham CE, Chung TT, Lawrance J, et al. Long-term experience of pegvisomant therapy as a treatment for acromegaly. Clinical Endocrinology. 2009;71(1):86-91. doi: https://doi.org/10.1111/j.1365-2265.2008.03469.xBuchfelder M, van der Lely AJ, Biller BMK, et al. Long-term treatment with pegvisomant: observations from 2090 acromegaly patients in ACROSTUDY. Eur J Endocrinol. 2018;179(6):419-427. doi: https://doi.org/10.1530/EJE-18-0616Buchfelder M, van der Lely AJ, Biller BMK, et al. Long-term treatment with pegvisomant: observations from 2090 acromegaly patients in ACROSTUDY. Eur J Endocrinol. 2018;179(6):419-427. doi: https://doi.org/10.1530/EJE-18-0616Yamaguchi H, Shimatsu A, Okayama A, Sato T. Long-term safety and treatment outcomes of pegvisomant in Japanese patients with acromegaly: results from the post-marketing surveillance. Endocr J. 2020;67(2):201-210. doi: https://doi.org/10.1507/endocrj.EJ19-0266Yamaguchi H, Shimatsu A, Okayama A, Sato T. Long-term safety and treatment outcomes of pegvisomant in Japanese patients with acromegaly: results from the post-marketing surveillance. Endocr J. 2020;67(2):201-210. doi: https://doi.org/10.1507/endocrj.EJ19-0266Giustina A. Optimal use of pegvisomant in acromegaly: are we getting there? Endocrine. 2015;48(1):3-8. doi: https://doi.org/10.1007/s12020-014-0462-0Giustina A. Optimal use of pegvisomant in acromegaly: are we getting there? Endocrine. 2015;48(1):3-8. doi: https://doi.org/10.1007/s12020-014-0462-0van der Lely AJ, Biller BMK, Brue T, et al. Long-term safety of pegvisomant in patients with acromegaly: comprehensive review of 1288 subjects in ACROSTUDY. J Clin Endocrinol Metab. 2012;97(5):1589-1597. doi: https://doi.org/10.1210/jc.2011-2508van der Lely AJ, Biller BMK, Brue T, et al. Long-term safety of pegvisomant in patients with acromegaly: comprehensive review of 1288 subjects in ACROSTUDY. J Clin Endocrinol Metab. 2012;97(5):1589-1597. doi: https://doi.org/10.1210/jc.2011-2508Colao A, Pivonello R, Auriemma RS, et al. Efficacy of 12-month treatment with the GH receptor antagonist pegvisomant in patients with acromegaly resistant to long-term, high-dose somatostatin analog treatment: effect on IGF-I levels, tumor mass, hypertension and glucose tolerance. Eur j Endocrinol. 2006;154(3):467-477. doi: https://doi.org/10.1530/eje.1.02112Colao A, Pivonello R, Auriemma RS, et al. Efficacy of 12-month treatment with the GH receptor antagonist pegvisomant in patients with acromegaly resistant to long-term, high-dose somatostatin analog treatment: effect on IGF-I levels, tumor mass, hypertension and glucose tolerance. Eur j Endocrinol. 2006;154(3):467-477. doi: https://doi.org/10.1530/eje.1.02112Parkinson C, Burman P, Messig M, Trainer PJ. Gender, Body Weight, Disease Activity, and Previous Radiotherapy Influence the Response to Pegvisomant. The Journal of Clinical Endocrinology & Metabolism. 2007;92(1):190-195. doi: https://doi.org/10.1210/jc.2006-1412Parkinson C, Burman P, Messig M, Trainer PJ. Gender, Body Weight, Disease Activity, and Previous Radiotherapy Influence the Response to Pegvisomant. The Journal of Clinical Endocrinology & Metabolism. 2007;92(1):190-195. doi: https://doi.org/10.1210/jc.2006-1412Sievers C, Baur DM, Schwanke A, et al. Prediction of therapy response in acromegalic patients under pegvisomant therapy within the German ACROSTUDY cohort. Pituitary. 2015;18(6):916-923. doi: https://doi.org/10.1007/s11102-015-0673-2Sievers C, Baur DM, Schwanke A, et al. Prediction of therapy response in acromegalic patients under pegvisomant therapy within the German ACROSTUDY cohort. Pituitary. 2015;18(6):916-923. doi: https://doi.org/10.1007/s11102-015-0673-2Colao A, Arnaldi G, Beck-Peccoz P, et al. Pegvisomant in acromegaly: Why, when, how. J Endocrinol Invest 2007;30(8):693-699. doi: https://doi.org/10.1007/BF03347452Colao A, Arnaldi G, Beck-Peccoz P, et al. Pegvisomant in acromegaly: Why, when, how. J Endocrinol Invest 2007;30(8):693-699. doi: https://doi.org/10.1007/BF03347452Droste M, Domberg J, Buchfelder M, et al. Therapy of acromegalic patients exacerbated by concomitant type 2 diabetes requires higher pegvisomant doses to normalise IGF1 levels. European Journal of Endocrinology. 2014;171(1):59-68. doi: https://doi.org/10.1530/EJE-13-0438Droste M, Domberg J, Buchfelder M, et al. Therapy of acromegalic patients exacerbated by concomitant type 2 diabetes requires higher pegvisomant doses to normalise IGF1 levels. European Journal of Endocrinology. 2014;171(1):59-68. doi: https://doi.org/10.1530/EJE-13-0438Katznelson L, Laws ER, Melmed S, et al. Endocrine Society Acromegaly: an endocrine society clinical practice guideline. J Clin Endocrinol Metab. 2014;99(11):3933-3951. doi: https://doi.org/10.1210/jc.2014-2700Katznelson L, Laws ER, Melmed S, et al. Endocrine Society Acromegaly: an endocrine society clinical practice guideline. J Clin Endocrinol Metab. 2014;99(11):3933-3951. doi: https://doi.org/10.1210/jc.2014-2700Giustina A, Ambrosio MR, Beck Peccoz P, et al. Use of Pegvisomant in acromegaly. An Italian Society of Endocrinology guideline. J Endocrinol Invest. 2014;37(10):1017-1030. doi: https://doi.org/10.1007/s40618-014-0146-xGiustina A, Ambrosio MR, Beck Peccoz P, et al. Use of Pegvisomant in acromegaly. An Italian Society of Endocrinology guideline. J Endocrinol Invest. 2014;37(10):1017-1030. doi: https://doi.org/10.1007/s40618-014-0146-xNeggers SJ, van der Lely AJ. Combination treatment with somatostatin analogues and pegvisomant in acromegaly. Growth Horm IGF Res. 2011;21(3):129-133. doi: https://doi.org/10.1016/j.ghir.2011.03.004Neggers SJ, van der Lely AJ. Combination treatment with somatostatin analogues and pegvisomant in acromegaly. Growth Horm IGF Res. 2011;21(3):129-133. doi: https://doi.org/10.1016/j.ghir.2011.03.004Neggers SJ, Franck SE, de Rooij FWM, et al. Long-term efficacy and safety of pegvisomant in combination with long-acting somatostatin analogs in acromegaly. J Clin Endocrinol Metab. 2014;99(10):3644-3652. doi: https://doi.org/10.1210/jc.2014-2032Neggers SJ, Franck SE, de Rooij FWM, et al. Long-term efficacy and safety of pegvisomant in combination with long-acting somatostatin analogs in acromegaly. J Clin Endocrinol Metab. 2014;99(10):3644-3652. doi: https://doi.org/10.1210/jc.2014-2032Ma L, Luo D, Yang T, et al. Combined therapy of somatostatin analogues with pegvisomant for the treatment of acromegaly: a meta-analysis of prospective studies. BMC Endocr Disord. 2020;20(1):126. doi: https://doi.org/10.1186/s12902-020-0545-2Ma L, Luo D, Yang T, et al. Combined therapy of somatostatin analogues with pegvisomant for the treatment of acromegaly: a meta-analysis of prospective studies. BMC Endocr Disord. 2020;20(1):126. doi: https://doi.org/10.1186/s12902-020-0545-2van der Lely AJ, Hutson RK, Trainer PJ, et al. Long-term treatment of acromegaly with pegvisomant, a growth hormone receptor antagonist. Lancet. 2001;358(9295):1754-1759. doi: https://doi.org/10.1016/s0140-6736(01)06844-1van der Lely AJ, Hutson RK, Trainer PJ, et al. Long-term treatment of acromegaly with pegvisomant, a growth hormone receptor antagonist. Lancet. 2001;358(9295):1754-1759. doi: https://doi.org/10.1016/s0140-6736(01)06844-1Higham CE, Atkinson AB, Aylwin S, et al. Effective Combination Treatment with Cabergoline and Low-Dose Pegvisomant in Active Acromegaly: A Prospective Clinical Trial. The Journal of Clinical Endocrinology & Metabolism. 2012;97(4):1187-1193. doi: https://doi.org/10.1210/jc.2011-2603Higham CE, Atkinson AB, Aylwin S, et al. Effective Combination Treatment with Cabergoline and Low-Dose Pegvisomant in Active Acromegaly: A Prospective Clinical Trial. The Journal of Clinical Endocrinology & Metabolism. 2012;97(4):1187-1193. doi: https://doi.org/10.1210/jc.2011-2603Giustina A, Chanson P, Kleinberg D, et al. Expert consensus document: A consensus on the medical treatment of acromegaly. Nat Rev Endocrinol. 2014;10(4):243-248. doi: https://doi.org/10.1038/nrendo.2014.21Giustina A, Chanson P, Kleinberg D, et al. Expert consensus document: A consensus on the medical treatment of acromegaly. Nat Rev Endocrinol. 2014;10(4):243-248. doi: https://doi.org/10.1038/nrendo.2014.21Tritos NA, Chanson P, Jimenez C, et al. Effectiveness of first-line pegvisomant monotherapy in acromegaly: an ACROSTUDY analysis. European Journal of Endocrinology. 2017;176(2):213-220. doi: https://doi.org/10.1530/EJE-16-0697Tritos NA, Chanson P, Jimenez C, et al. Effectiveness of first-line pegvisomant monotherapy in acromegaly: an ACROSTUDY analysis. European Journal of Endocrinology. 2017;176(2):213-220. doi: https://doi.org/10.1530/EJE-16-0697Мачехина Л.В., Шестакова Е.А., Белая Ж.Е., и др. Особенности углеводного обмена и секреции гормонов инкретинового ряда у пациентов с болезнью Иценко-Кушинга и акромегалией // Сахарный диабет. — 2017. — T. 20. — № 4. — C. 249-256. doi: https://doi.org/10.14341/DM8762Machekhina LV, Shestakova EA, Belaya ZhE, et al. Features of carbohydrate metabolism and incretin secretion in patients with Cushing’s disease and acromegaly. Diabetes Mellitus. 2017;20(4):249-256. (In Russ.). doi: https://doi.org/10.14341/DM8762Pivonello R, Auriemma RS, Grasso LFS, et al. Complications of acromegaly: cardiovascular, respiratory and metabolic comorbidities. Pituitary 2017; 20(1): 46–62. doi: https://doi.org/10.1007/s11102-017-0797-7Pivonello R, Auriemma RS, Grasso LFS, et al. Complications of acromegaly: cardiovascular, respiratory and metabolic comorbidities. Pituitary 2017; 20(1): 46–62. doi: https://doi.org/10.1007/s11102-017-0797-7Briet C, Ilie MD, Kuhn E, et al. Changes in metabolic parameters and cardiovascular risk factors after therapeutic control of acromegaly vary with the treatment modality. Data from the Bicêtre cohort, and review of the literature. Endocrine. 2019;63(2):348-360. doi: https://doi.org/10.1007/s12020-018-1797-8Briet C, Ilie MD, Kuhn E, et al. Changes in metabolic parameters and cardiovascular risk factors after therapeutic control of acromegaly vary with the treatment modality. Data from the Bicêtre cohort, and review of the literature. Endocrine. 2019;63(2):348-360. doi: https://doi.org/10.1007/s12020-018-1797-8Colao A, Auriemma RS, Savastano S, et al. Glucose Tolerance and Somatostatin Analog Treatment in Acromegaly: A 12-Month Study. The Journal of Clinical Endocrinology & Metabolism. 2009;94(8):2907-2914. doi: https://doi.org/10.1210/jc.2008-2627Colao A, Auriemma RS, Savastano S, et al. Glucose Tolerance and Somatostatin Analog Treatment in Acromegaly: A 12-Month Study. The Journal of Clinical Endocrinology & Metabolism. 2009;94(8):2907-2914. doi: https://doi.org/10.1210/jc.2008-2627Ronchi CL, Orsi E, Giavoli C, et al. Evaluation of insulin resistance in acromegalic patients before and after treatment with somatostatin analogues. J Endocrinol Invest. 2003;26(6):533-538. doi: https://doi.org/10.1007/BF03345216Ronchi CL, Orsi E, Giavoli C, et al. Evaluation of insulin resistance in acromegalic patients before and after treatment with somatostatin analogues. J Endocrinol Invest. 2003;26(6):533-538. doi: https://doi.org/10.1007/BF03345216Barbot M, Regazzo D, Mondin A, et al. Is pasireotide-induced diabetes mellitus predictable? A pilot study on the effect of a single dose of pasireotide on glucose homeostasis. Pituitary 2020;23(5):534-542. doi: https://doi.org/10.1007/s11102-020-01055-xBarbot M, Regazzo D, Mondin A, et al. Is pasireotide-induced diabetes mellitus predictable? A pilot study on the effect of a single dose of pasireotide on glucose homeostasis. Pituitary 2020;23(5):534-542. doi: https://doi.org/10.1007/s11102-020-01055-xSingh V, Brendel MD, Zacharias S, et al. Characterization of somatostatin receptor subtype-specific regulation of insulin and glucagon secretion: an in vitro study on isolated human pancreatic islets. J Clin Endocrinol Metab. 2007;92(2):673-680. doi: https://doi.org/10.1210/jc.2006-1578Singh V, Brendel MD, Zacharias S, et al. Characterization of somatostatin receptor subtype-specific regulation of insulin and glucagon secretion: an in vitro study on isolated human pancreatic islets. J Clin Endocrinol Metab. 2007;92(2):673-680. doi: https://doi.org/10.1210/jc.2006-1578Hannon AM, Thompson CJ, Sherlock M. Diabetes in Patients with Acromegaly. Curr Diab Rep. 2017;17(2):8. doi: https://doi.org/10.1007/s11892-017-0838-7Hannon AM, Thompson CJ, Sherlock M. Diabetes in Patients with Acromegaly. Curr Diab Rep. 2017;17(2):8. doi: https://doi.org/10.1007/s11892-017-0838-7Ghigo E, Biller BMK, Colao A, et al. Comparison of pegvisomant and long-acting octreotide in patients with acromegaly naïve to radiation and medical therapy. J Endocrinol Invest 2009;32(11):924-933. doi: https://doi.org/10.1007/BF03345774Ghigo E, Biller BMK, Colao A, et al. Comparison of pegvisomant and long-acting octreotide in patients with acromegaly naïve to radiation and medical therapy. J Endocrinol Invest 2009;32(11):924-933. doi: https://doi.org/10.1007/BF03345774Дзеранова Л.К., Поваляева А.А., Романова А.А., и др. Пэгвисомант и современные подходы к медикаментозному лечению акромегалии (обзор литературы и описание клинического случая) // Ожирение и метаболизм. — 2019. — T. 16. — №4. — C. 73-79. doi: https://doi.org/10.14341/omet12207Dzeranova LK, Povaliaeva AA, Romanova AA, et al. Pegvisomant and current approaches to the medical treatment of acromegaly (literature review and case report). Obes Metabol. 2020;16(4):73-79. (In Russ.). doi: https://doi.org/10.14341/omet12207Cozzolino A, Feola T, Simonelli I, et al. Somatostatin Analogs and Glucose Metabolism in Acromegaly: A Meta-Analysis of Prospective Interventional Studies. J Clin Endocrinol Metab. 2018;103(6):2089-2099. doi: https://doi.org/10.1210/jc.2017-02566Cozzolino A, Feola T, Simonelli I, et al. Somatostatin Analogs and Glucose Metabolism in Acromegaly: A Meta-Analysis of Prospective Interventional Studies. J Clin Endocrinol Metab. 2018;103(6):2089-2099. doi: https://doi.org/10.1210/jc.2017-02566Shen M, Wang M, He W, et al. Impact of Long-Acting Somatostatin Analogues on Glucose Metabolism in Acromegaly: A Hospital-Based Study. Int J Endocrinol. 2018;2018:1-10. doi: https://doi.org/10.1155/2018/3015854Shen M, Wang M, He W, et al. Impact of Long-Acting Somatostatin Analogues on Glucose Metabolism in Acromegaly: A Hospital-Based Study. Int J Endocrinol. 2018;2018:1-10. doi: https://doi.org/10.1155/2018/3015854Ferraù F, Albani A, Ciresi A, et al. Diabetes Secondary to Acromegaly: Physiopathology, Clinical Features and Effects of Treatment. Front Endocrinol (Lausanne). 2018;9:358. doi: https://doi.org/10.3389/fendo.2018.00358Ferraù F, Albani A, Ciresi A, et al. Diabetes Secondary to Acromegaly: Physiopathology, Clinical Features and Effects of Treatment. Front Endocrinol (Lausanne). 2018;9:358. doi: https://doi.org/10.3389/fendo.2018.00358Vila G, Jørgensen JOL, Luger A, Stalla GK. Insulin Resistance in Patients with Acromegaly. Front Endocrinol (Lausanne). 2019;10:509. doi: https://doi.org/10.3389/fendo.2019.00509Vila G, Jørgensen JOL, Luger A, Stalla GK. Insulin Resistance in Patients with Acromegaly. Front Endocrinol (Lausanne). 2019;10:509. doi: https://doi.org/10.3389/fendo.2019.00509Brue T, Lindberg A, Jan van der Lely A, et al. Diabetes in patients with acromegaly treated with pegvisomant: observations from acrostudy. Endocrine 2019;63(3):563-572. doi: https://doi.org/10.1007/s12020-018-1792-0Brue T, Lindberg A, Jan van der Lely A, et al. Diabetes in patients with acromegaly treated with pegvisomant: observations from acrostudy. Endocrine 2019;63(3):563-572. doi: https://doi.org/10.1007/s12020-018-1792-0Feola T, Cozzolino A, Simonelli I, et al. Pegvisomant Improves Glucose Metabolism in Acromegaly: A Meta-Analysis of Prospective Interventional Studies. J Clin Endocrinol Metab 2019;104(7):2892-2902. doi: https://doi.org/10.1210/jc.2018-02281Feola T, Cozzolino A, Simonelli I, et al. Pegvisomant Improves Glucose Metabolism in Acromegaly: A Meta-Analysis of Prospective Interventional Studies. J Clin Endocrinol Metab 2019;104(7):2892-2902. doi: https://doi.org/10.1210/jc.2018-02281Franck SE, Muhammad A, van der Lely AJ, Neggers SJ. Combined treatment of somatostatin analogues with pegvisomant in acromegaly. Endocrine 2016;52(2):206-213. doi: https://doi.org/10.1007/s12020-015-0810-8Franck SE, Muhammad A, van der Lely AJ, Neggers SJ. Combined treatment of somatostatin analogues with pegvisomant in acromegaly. Endocrine 2016;52(2):206-213. doi: https://doi.org/10.1007/s12020-015-0810-8De Marinis L, Bianchi A, Fusco A, et al. Long-term effects of the combination of pegvisomant with somatostatin analogs (SSA) on glucose homeostasis in non-diabetic patients with active acromegaly partially resistant to SSA. Pituitary 2007;10(3):227-232. doi: https://doi.org/10.1007/s11102-007-0037-7De Marinis L, Bianchi A, Fusco A, et al. Long-term effects of the combination of pegvisomant with somatostatin analogs (SSA) on glucose homeostasis in non-diabetic patients with active acromegaly partially resistant to SSA. Pituitary 2007;10(3):227-232. doi: https://doi.org/10.1007/s11102-007-0037-7Corica G, Ceraudo M, Campana C, et al. Octreotide-Resistant Acromegaly: Challenges and Solutions. Ther Clin Risk Manag. 2020;16:379-391. doi: https://doi.org/10.2147/TCRM.S183360Corica G, Ceraudo M, Campana C, et al. Octreotide-Resistant Acromegaly: Challenges and Solutions. Ther Clin Risk Manag. 2020;16:379-391. doi: https://doi.org/10.2147/TCRM.S183360

The authors declare that there are no conflicts of interest present.