ometendoОжирение и метаболизмObesity and metabolism2071-87132306-5524Endocrinology Research Centre10.14341/omet13153ometendo-13153Research ArticleКЛИНИЧЕСКИЕ РЕКОМЕНДАЦИИCLINICAL PRACTICE GUIDELINESКлинические рекомендации «Акромегалия» (проект)Guidelines on diagnostics and treatment of acromegaly (draft)https://orcid.org/0000-0001-9119-2447ПржиялковскаяЕ. Г.PrzhiyalkovskayaE. G.

Пржиялковская Елена Георгиевна, к.м.н.

117036, Москва, ул. Дм. Ульянова, д. 11 

Elena G. Przhiyalkovskaya, MD, PhD

11 Dm. Ulyanova street, 117036 Moscow

przhiyalkovskaya.elena@gmail.comhttps://orcid.org/0000-0002-9717-9742МокрышеваН. Г.MokryshevaN. G.

Мокрышева Наталья Георгиевна, д.м.н., профессор 

Москва

Natalia G. Mokrysheva, MD, PhD, Professor

Moscow

mokrisheva.natalia@endocrincentr.ruhttps://orcid.org/0000-0002-8520-8702ТрошинаЕ. А.TroshinaE. A.

Трошина Екатерина Анатольевна, д.м.н., профессор 

Москва

Ekaterina A. Troshina, MD, PhD, Professor

Moscow

troshina.ekaterina@endocrincentr.ruhttps://orcid.org/0000-0002-5634-7877МельниченкоГ. А.MelnichenkoG. A.

Мельниченко Галина Афанасьевна, д.м.н., профессор 

Москва

Galina A. Melnichenko, MD, PhD, professor

Moscow

teofrast2000@mail.ruhttps://orcid.org/0000-0002-8175-7886ДедовИ. И.DedovI. I.

Дедов Иван Иванович, д.м.н., профессор, академик

Москва

Ivan I. Dedov, MD, PhD, Professor, Academician of the Russian Academy of Sciences

Moscow

dedov@endocrincentr.ruhttps://orcid.org/0000-0002-9944-2997АнциферовМ. Б.AntsiferovM. B.

Анциферов Михаил Борисович, д.м.н., профессор

Москва

Mikhail B. Antsiferov, MD, PhD, professor

Moscow

antsiferov@rambler.ruhttps://orcid.org/0000-0003-4480-1902АстафьеваЛ. И.AstafievaL. I.

Астафьева Людмила Игоревна, д.м.н.

Москва

Liudmila I. Astafyeva, MD, PhD

Moscow

last@nsi.ruhttps://orcid.org/0000-0003-4241-2217БардымоваТ. П.BardymovaT. P.

Бардымова Татьяна Прокопьевна, д.м.н., профессор

Иркутск

Tatiana P. Bardymova, MD, PhD, professor

Irkutsk 

tpbardymova@mail.ruhttps://orcid.org/0000-0002-6674-6441БелаяЖ. Е.BelayaZh. E.

Белая Жанна Евгеньевна, д.м.н. 

Москва

Zhanna E. Belaya, MD, PhD

Moscow

jannabelaya@gmail.comВагаповаГ. Р.VagapovaG. R.

Вагапова Гульнара Рифатовна, д.м.н., проф.

Казань

Gulnar R. Vagapova, MD, PhD, professor

Kazan

https://orcid.org/0000-0001-7470-1676ВоротниковаС. Ю.VorotnikovaS. Yu.

Воротникова Светлана Юрьевна, к.м.н.

Москва

 

Svetlana Y. Vorotnikova, MD, PhD

Moscow

bra_svetix@list.ruhttps://orcid.org/0000-0002-9575-4520ГригорьевА. Ю.GrigorievA. Yu.

Григорьев Андрей Юрьевич, д.м.н., профессор 

Москва

Andrey Y. Grigoriev, MD, PhD, Professor

Moscow

medway@list.ruhttps://orcid.org/0000-0003-0042-7680ГриневаЕ. Н.GrinevaE. N.

Гринева Елена Николаевна, д.м.н., профессор 

Санкт-Петербург

Elena N. Grineva, MD, PhD, Professor

St. Petersburg

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

Дзеранова Лариса Константиновна, д.м.н. 

Москва

Larisa K. Dzeranova, MD, Sc.D.

Moscow

dzeranova.Larisa@endocrincentr.ruhttps://orcid.org/0000-0003-3261-7366ИловайскаяИ. А.IlovaiskayaI. A.

Иловайская Ирэна Адольфовна, д.м.н., доцент 

Москва

Irena A. Ilovaуskaya, MD, PhD, Рrofessor

Moscow

irena.ilov@yandex.ruhttps://orcid.org/0000-0001-9333-9473КалининП. Л.KalininP. L.

Калинин Павел Львович, д.м.н. 

Москва

Pavel L. Kalinin, MD, PhD

Moscow

PKalinin@nsi.ruhttps://orcid.org/0000-0003-4353-6705ЛапшинаА. М.LapshinaA. M.

Лапшина Анастасия Михайловна, к.м.н.

Москва

Anastasia M. Lapshina, MD, PhD

Moscow

nottoforget@yandex.ruhttps://orcid.org/0000-0002-9314-7831ЛуценкоА. С.LutsenkoA. S.

Луценко Александр Сергеевич

117036, Москва, ул. Дм. Ульянова, д. 11

Alexander S. Lutsenko, MD

11 Dm. Ulyanova street, 117036 Moscow

some91@mail.ruhttps://orcid.org/0000-0002-9783-3599МамедоваЕ. О.MamedovaE. O.

Мамедова Елизавета Октаевна, к.м.н. 

Москва

Elizaveta O. Mamedova, MD, PhD

Moscow

lilybet@mail.ruhttps://orcid.org/0000-0002-5130-4157МароваЕ. И.MarovaE. I.

Марова Евгения Ивановна, д.м.н., профессор 

Москва

Evgenia I. Marova, MD, PhD, professor

Moscow

marova-e@mail.ruhttps://orcid.org/0000-0001-5824-6490ПерепеловаМ. А.PerepelovaM. A.

Перепелова Маргарита Александровна, аспирант

Москва

Margarita A. Perepelova, MD, postgraduate student

Moscow

margo.doktor@mail.ruhttps://orcid.org/0000-0001-6539-466XПигароваЕ. А.PigarovaE. A.

Пигарова Екатерина Александровна, д.м.н. 

Москва

Ekaterina A. Pigarova, MD, PhD

Moscow

kpigarova@gmail.comhttps://orcid.org/0000-0001-5045-798XПронинВ. С.ProninV. S.

Пронин Вячеслав Сергеевич, д.м.н., профессор 

Москва

Vyacheslav S. Pronin, MD., PhD, professor

Moscow

vspronin@yandex.ruhttps://orcid.org/0000-0001-7041-0732РожинскаяЛ. Я.RozhinskayaL. Ya.

Рожинская Людмила Яковлевна, д.м.н., профессор

 Москва

Liudmila Ya. Rozhinskaya, MD, PhD, Professor

Moscow

lrozhinskaya@gmail.comhttps://orcid.org/0000-0002-4240-5036ТрунинЮ. Ю.TruninYu. Yu.

Трунин Юрий Юрьевич, д.м.н. 

Москва

Yuri Yu. Trunin, MD, PhD

Moscow

ytrunin@nsi.ruhttps://orcid.org/0000-0003-0047-7223ШутоваА. С.ShutovaA. S.

Шутова Александра Сергеевна

Москва

Aleksandra S. Shutova, MD, postgraduate student

Moscow

shutova.aleksandra@gmail.comНациональный медицинский исследовательский центр эндокринологииРоссияEndocrinology Research CentreRussian FederationЭндокринологический диспансер Департамента здравоохранения города МосквыРоссияEndocrinological Dispensary of the Moscow City Health DepartmentRussian FederationНациональный медицинский исследовательский центр нейрохирургии им. ак. Н.Н. БурденкоРоссияNational Medical Research Center of Neurosurgery named after. ak. N.N. BurdenkoRussian FederationРоссийская медицинская академия непрерывного профессионального образования, Иркутская государственная медицинская академия последипломного образования — филиалРоссияIrkutsk State Medical Academy of Postgraduate Education — branch of the Russian Medical Academy of Continuing Professional EducationRussian FederationКазанская государственная медицинская академияРоссияKazan State Medical AcademyRussian FederationНациональный медицинский исследовательский центр имени В.А. АлмазоваРоссияNational Medical Research Center named after V. A. AlmazovRussian FederationМосковский областной научно-исследовательский клинический институт им. М. Ф. ВладимирскогоРоссияMoscow Regional Research and Clinical Institute named after M. F. VladimirskyRussian FederationРоссийская медицинская академия непрерывного профессионального образованияРоссияRussian Medical Academy of Continuing Professional EducationRussian Federation202426062024212215249Copyright © Пржиялковская Е.Г., Мокрышева Н.Г., Трошина Е.А., Мельниченко Г.А., Дедов И.И., Анциферов М.Б., Астафьева Л.И., Бардымова Т.П., Белая Ж.Е., Вагапова Г.Р., Воротникова С.Ю., Григорьев А.Ю., Гринева Е.Н., Дзеранова Л.К., Иловайская И.А., Калинин П.Л., Лапшина А.М., Луценко А.С., Мамедова Е.О., Марова Е.И., Перепелова М.А., Пигарова Е.А., Пронин В.С., Рожинская Л.Я., Трунин Ю.Ю., Шутова А.С., 20242024Пржиялковская Е.Г., Мокрышева Н.Г., Трошина Е.А., Мельниченко Г.А., Дедов И.И., Анциферов М.Б., Астафьева Л.И., Бардымова Т.П., Белая Ж.Е., Вагапова Г.Р., Воротникова С.Ю., Григорьев А.Ю., Гринева Е.Н., Дзеранова Л.К., Иловайская И.А., Калинин П.Л., Лапшина А.М., Луценко А.С., Мамедова Е.О., Марова Е.И., Перепелова М.А., Пигарова Е.А., Пронин В.С., Рожинская Л.Я., Трунин Ю.Ю., Шутова А.С.Przhiyalkovskaya E.G., Mokrysheva N.G., Troshina E.A., Melnichenko G.A., Dedov I.I., Antsiferov M.B., Astafieva L.I., Bardymova T.P., Belaya Z.E., Vagapova G.R., Vorotnikova S.Y., Grigoriev A.Y., Grineva E.N., Dzeranova L.K., Ilovaiskaya I.A., Kalinin P.L., Lapshina A.M., Lutsenko A.S., Mamedova E.O., Marova E.I., Perepelova M.A., Pigarova E.A., Pronin V.S., Rozhinskaya L.Y., Trunin Y.Y., Shutova A.S.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/13153

Всем пациентам с характерными изменениями внешности рекомендуется исключать акромегалию (А3). Всем пациентам без характерных изменений внешности при наличии нескольких подозрительных в отношении акромегалии клинических признаков рекомендуется исключать акромегалию (B3). Всем пациентам c аденомой гипофиза рекомендуется исключать акромегалию (B3). У всех пациентов с пролактин-секретирующими аденомами рекомендуется исключать акромегалию (C4). Всем пациентам для лабораторного подтверждения акромегалии рекомендуется исследование уровня инсулиноподобного фактора роста-1 (ИФР-1, соматомедина С) в крови (A3). У пациентов без явных клинических признаков акромегалии и/или с умеренным повышением уровня ИФР-1 (ИФР-1 индекс менее 1,3), для лабораторного подтверждения акромегалии рекомендуется определение реакции соматотропного гормона (СТГ) на гипергликемию (СТГ в ходе перорального глюкозотолерантного теста) (B3). Всем пациентам при лабораторном подтверждении акромегалии рекомендуется проведение магнитно-резонансной томографии гипофиза с внутривенным контрастированием для определения размера, расположения и характера роста аденомы гипофиза (A3). Всем пациентам с подтвержденной акромегалией рекомендуется исследование уровня глюкозы в крови и исследование уровня гликированного гемоглобина в крови для выявления нарушений углеводного обмена (B3). Всем пациентам с акромегалией рекомендуется исследование уровня пролактина в крови для исключения гиперпролактинемии (B3).

Всем пациентам с акромегалией и аденомой гипофиза в качестве первой линии лечения рекомендуется проведение трансназальной транссфеноидальной аденомэктомии при согласии пациента и отсутствии противопоказаний (A1). Всем пациентам с акромегалией, которым показано нейрохирургическое лечение, проведение оперативного вмешательства рекомендуется в специализирующихся на заболеваниях гипофиза медицинских учреждениях нейрохирургами, выполняющими не менее 50 подобных операций в год (A3). Всем пациентам с акромегалией после нейрохирургического лечения рекомендуется морфологическое и иммуногистохимическое исследование удаленной аденомы гипофиза (A3). Рутинное назначение медикаментозной терапии акромегалии перед проведением оперативного вмешательства для уменьшения размера опухоли не рекомендуется (B2).

Пациентам с акромегалией, у которых нейрохирургическое лечение было невозможно, неэффективно, а также ожидающим эффект лучевой терапии рекомендована медикаментозная терапия (A1). В качестве первой линии медикаментозной терапии акромегалии рекомендуется применение аналогов соматостатина пролонгированного действия первого поколения (A1). При частичной/полной резистентности к аналогам соматостатина или их непереносимости в качестве второй линии медикаментозной терапии акромегалии рекомендуется назначение пэгвисоманта (A1). Пациентам с акромегалией для инициации терапии пэгвисомантом рекомендуется однократно ввести нагрузочную дозу 40–80 мг в сутки подкожно, далее продолжать инъекции в стартовой дозе 10 или 15 мг в сутки с контролем уровня ИФР-1 через 4–6 недель и коррекцией дозы при необходимости (B2). Пациентам с акромегалией и умеренным повышением уровня ИФР-1 рекомендуется назначение каберголина в качестве медикаментозной монотерапии или при неэффективности аналогов соматостатина — в комбинации с ними (B2).

Пациентам с акромегалией в случаях сохранения активности заболевания после хирургического лечения, при недоступности, непереносимости или неэффективности медикаментозного лечения и нецелесообразности повторного нейрохирургического вмешательства рекомендуется проводить лучевую терапию (A1). Рекомендуется мультидисциплинарный подход в лечении осложнений акромегалии (C3).

We recommend acromegaly to be ruled in all patients with characteristic changes in appearance (A3). In all patients without characteristic changes in appearance, we recommend to rule out acromegaly, if several clinical signs suspicious for acromegaly are present (B3). We recommend acromegaly to be ruled out in all patients with pituitary adenoma (B3). We recommend to rule out acromegaly in all patients with prolactin-secreting adenomas (C4). For laboratory confirmation of acromegaly, we recommend to measure serum insulin-like growth factor-1 (IGF-1, somatomedin C) level (A3). In patients without obvious clinical signs of acromegaly and/or with a moderate increase in IGF-1 levels (IGF-1 index less than 1.3), we recommend to assess the response of somatotropic hormone (GH) to hyperglycemia (GH during an oral glucose tolerance test) (B3). In all patients with biochemically confirmed acromegaly, magnetic resonance imaging of the pituitary gland with intravenous contrast is recommended to assess pituitary adenoma size, location and growth pattern (A3). We recommend to measure blood glucose and glycated hemoglobin in all patients with confirmed acromegaly (B3). We recommend to measure serum prolactin levels in all patients with acromegaly (B3).

In all patients with acromegaly and pituitary adenoma, transnasal transsphenoidal adenomectomy is recommended as first-line treatment if the patient’s consent is given and there are no contraindications (A1). For all patients with acromegaly for whom neurosurgical treatment is indicated, surgical intervention is recommended in medical centers, specializing in pituitary diseases, by neurosurgeons who perform at least 50 such operations per year (A3). We recommend that morphological and immunohistochemical examination of the removed pituitary adenoma is performed in all patients with acromegaly (A3). We do not recommend routine medical therapy for acromegaly before surgery as a mean to reduce tumor size (B2).

For patients with acromegaly in whom neurosurgical treatment is not indicated or ineffective or while patient awaiting for the effect of radiation therapy, we recommend medical therapy (A1). Long-acting first-generation somatostatin analogues are recommended as first-line drug therapy for acromegaly. In case of partial/complete resistance to or intolerance to somatostatin analogs, pegvisomant is recommended as a second-line medical therapy for acromegaly (A1). We recommend starting pegvisomant from a single dose of 40–80 mg per day subcutaneously, then continue injections at a starting dose of 10 or 15 mg per day with IGF-1 monitoring after 4–6 weeks and dose adjustment if necessary (B2). In patients with acromegaly and a moderate increase in IGF-1 levels, we recommend to initiate cabergoline as medical monotherapy or, if somatostatin analogs are ineffective, in combination with them (B2).

In patients with acromegaly, if the disease remains active after surgical treatment, if drug treatment is unavailable, intolerable or ineffective, and repeated neurosurgical intervention is inappropriate, it is we recommend radiation therapy (A1). A multidisciplinary approach is recommended in the management of acromegaly complications (C3).

акромегалияаденома гипофизасоматотропный гормонинсулиноподобный фактор роста-1октреотидланреотидпэгвисомантacromegalypituitary adenomagrowth hormoneinsulin-like growth factor-1octreotidelanreotidepegvisomantReferencesColao A, Grasso LFS, Giustina A, et al. Acromegaly. Nat Rev Dis Primers. 2019;5(1). doi: https://doi.org/10.1038/s41572-019-0071-6Colao A, Grasso LFS, Giustina A, et al. Acromegaly. Nat Rev Dis Primers. 2019;5(1). doi: https://doi.org/10.1038/s41572-019-0071-6Дедов И.И., Мельниченко Г.А. Акромегалия: Патогенез, Клиника, Диагностика, Дифференциальная Диагностика, Методы Лечения. Пособие Для Врачей. — М.; 2012.Dedov II, Mel’nichenko GA. Akromegaliya: Patogenez, Klinika, Diagnostika, Differentsial’naya Diagnostika, Metody Lecheniya. Posobie Dlya Vrachey. Moscow; 2012. (In Russ).Katznelson L, Laws ER, Melmed S, et al. 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. Acromegaly: An Endocrine Society Clinical Practice Guideline. J Clin Endocrinol Metab. 2014;99(11):3933-3951. doi: https://doi.org/10.1210/JC.2014-2700Пронин В.С., Молитвословова Н.Н. Акромегалия. Этиология, Патогенез, Клиника, Диагностика, Лечение. / Под ред. Дедова И.И., Мельниченко Г.А. М; 2009.Pronin VS, Molitvoslovova NN. Akromegaliya. Etiologiya, Patogenez, Klinika, Diagnostika, Lechenie. / Ed by Dedov II, Mel’nichenko GA. Moscow; 2009 (In Russ).Cuevas-Ramos D, Carmichael JD, Cooper O, et al. A structural and functional acromegaly classification. J Clin Endocrinol Metab. 2015;100(1):122-131. doi: https://doi.org/10.1210/jc.2014-2468Cuevas-Ramos D, Carmichael JD, Cooper O, et al. A structural and functional acromegaly classification. 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The authors declare that there are no conflicts of interest present.