Almanac of Clinical MedicineAlmanac of Clinical MedicineАльманах клинической медицины2072-05052587-9294Moscow Regional Research and Clinical Institute (MONIKI)1716110.18786/2072-0505-2023-51-037REVIEW ARTICLEОБЗОРReview ArticleDiabetes mellitus in acromegaly: prevalence, pathophysiological particulars and treatment strategiesСахарный диабет при акромегалии: частота, особенности патогенеза и подходы к лечениюhttps://orcid.org/0000-0003-3261-7366IlovayskayaIrena A.ИловайскаяИрэна Адольфовна
Russian Federation

MD, PhD, Professor, Head of Department of Neuroendocrinal Diseases, Unit of General Endocrinology

д-р мед. наук, доцент, руководитель отделения нейроэндокринных заболеваний отдела общей эндокринологии

irena.ilov@yandex.ruhttps://orcid.org/0000-0001-6581-4521GalstyanGagik R.ГалстянГагик Радикович
Russian Federation

MD, PhD, Professor, Head of Unit of General Endocrinology;Head of Department of Diabetic Foot

д-р мед. наук, профессор, руководитель отдела общей эндокринологии; заведующий отделением диабетической стопы

galstyangagik964@gmail.comMoscow Regional Research and Clinical Institute (MONIKI)ГБУЗ МО «Московский областной научно-исследовательский клинический институт им. М.Ф. Владимирского»Endocrinology Research CentreФГБУ «Национальный медицинский исследовательский центр эндокринологии» Минздрава России091220235163443542710202327112023Copyright ©; 2023, Ilovayskaya I.A., Galstyan G.R.Copyright ©; 2023, Иловайская И.А., Галстян Г.Р.2023Ilovayskaya I.A., Galstyan G.R.Иловайская И.А., Галстян Г.Р.https://creativecommons.org/licenses/by-nc/4.0https://almclinmed.ru/jour/article/view/17161

The prevalence of diabetes mellitus in acromegaly is significantly higher than that in the general population. Carbohydrate metabolism abnormalities often precede other phenotypic manifestations of acromegaly. The review presents data on the prevalence of carbohydrate metabolism disorders in acromegaly and describes their pathophysiological characteristics and approaches to treatment.

Growth hormone (GH) excess is recognized as a key factor of glucose homeostasis abnormalities due to decreased insulin sensitivity (resulting from active lipolysis) and direct stimulation of insulin secretion. Insulin-like growth factor 1 (IGF1) improves insulin sensitivity; however, the GH diabetogenic effects prevail over the insulin-sensitizing impact of IGF1. Surgical and radiation treatment for somatotropinoma may indirectly improve carbohydrate metabolism, because they decrease the GH levels. Treatment with first generation somatostatin analogues can both improve glycemic control due to decreased GH levels and worsen it due to deterioration of postprandial insulin release, especially in patients with already manifest carbohydrate metabolism disorders. The GH receptor antagonist pegvisomant blocks the effects of excess GH on the target tissues without suppressing insulin secretion, which results in better glucose control; treatment with this agent can be preferred in patients with acromegaly and diabetes mellitus. Management of carbohydrate metabolism disorders in acromegaly is done in accordance with general treatment principles for type 2 diabetes mellitus.

Частота сахарного диабета при акромегалии значительно превышает таковую в общей популяции, и нарушения углеводного обмена часто предшествуют появлению других фенотипических проявлений акромегалии. В настоящем обзоре представлены данные о частоте нарушений углеводного обмена при акромегалии, описаны особенности патогенеза и подходы к лечению.

Избыток гормона роста (ГР) признан ключевым фактором нарушений гомеостаза глюкозы за счет снижения чувствительности к инсулину (вследствие активного липолиза) и прямого стимулирующего действия на секрецию инсулина. Инсулиноподобный ростовой фактор 1-го типа (ИРФ-1) повышает чувствительность к инсулину, однако диабетогенное действие ГР преобладает над инсулин-сенсибилизирующим действием ИРФ-1. Хирургические и лучевые методы воздействия на соматотропиному опосредованно улучшают углеводный обмен, так как снижается уровень ГР. На фоне лечения аналогами соматостатина первого поколения можно наблюдать как улучшение гликемического контроля вследствие уменьшения уровня ГР, так и его ухудшение за счет нарушения постпрандиального выброса инсулина (особенно у пациентов с уже имеющимися нарушениями углеводного обмена). Антагонист рецепторов ГР пэгвисомант блокирует действие избытка ГР на ткани-мишени без подавляющего влияния на секрецию инсулина, что приводит к повышению эффективности контроля углеводного обмена; этот вид лечения может быть предпочтителен у пациентов с акромегалией и сахарным диабетом. Лечение нарушений углеводного обмена при акромегалии проводится в соответствии с общими подходами к терапии сахарного диабета 2-го типа.

acromegalycarbohydrate metabolism disordersdiabetes mellitusgrowth hormonesomatotropinomasomatostatin analoguesgrowth hormone receptor antagonistакромегалиянарушения углеводного обменасахарный диабетгормон ростасоматотропиномааналоги соматостатинаантагонисты рецепторов гормона ростаDedov II, Molitvoslovova NN, Rozhinskaia LI, Mel'nichenko GA. [Russian Association of Endocrinologists National Practice Guidelines (clinical signs, diagnosis, differential diagnosis, treatment). Acromegaly]. Problems of Endocrinology. 2013;59(6):4–18. Russian. doi: 10.14341/probl20135964-18.Дедов ИИ, Молитвословова НН, Рожинская ЛЯ, Мельниченко ГА. Федеральные клинические рекомендации по клинике, диагностике, дифференциальной диагностике и методам лечения акромегалии. Проблемы Эндокринологии. 2013;59(6):4–18. doi: 10.14341/probl20135964-18.Fleseriu M, Langlois F, Lim DST, Varlamov EV, Melmed S. Acromegaly: pathogenesis, diagnosis, and management. Lancet Diabetes Endocrinol. 2022;10(11):804–826. doi: 10.1016/S2213-8587(22)00244-3.Belaya ZE, Golounina OO, Rozhinskaya LY, Melnichenko GA, Isakov MА, Lutsenko AS, Alekseeva T, Zenkova TS, Przhiyalkovskaya EG, Panyushkina GM, Ilukhina OB, Ivanova EI, Krishtal EA, Vachygova AA, Pigarova EA, Dzeranova LK, Marova EI, Arapova SD, Mamedova EO, Grebennikova TA, Antsiferov MB, Dreval AV, Dedov II. [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. Russian. doi: 10.14341/probl10333.Белая ЖЕ, Голоунина ОО, Рожинская ЛЯ, Мельниченко ГА, Исаков МА, Луценко АС, Алексеева ТМ, Зенкова ТС, Пржиялковская ЕГ, Панюшкина ГМ, Илюхина ОБ, Иванова ЕИ, Кришталь ЕА, Вачугова АА, Пигарова ЕА, Дзеранова ЛК, Марова ЕИ, Арапова СД, Мамедова ЕО, Гребенникова ТА, Анциферов МБ, Древаль АВ, Дедов ИИ. Эпидемиология, клинические проявления и эффективность различных методов лечения акромегалии по данным единого Российского регистра опухолей гипоталамо-гипофизарной системы. Проблемы Эндокринологии. 2020;66(1):93–103. doi: 10.14341/probl10333.Lavrentaki A, Paluzzi A, Wass JA, Karavitaki N. Epidemiology of acromegaly: review of population studies. Pituitary. 2017;20(1):4–9. doi: 10.1007/s11102-016-0754-x.Esposito D, Olsson DS, Franzén S, Miftaraj M, Nåtman J, Gudbjörnsdottir S, Johannsson G. Effect of Diabetes on Morbidity and Mortality in Patients With Acromegaly. J Clin Endocrinol Metab. 2022;107(9):2483–2492. doi: 10.1210/clinem/dgac400.Dedov II, Shestakova MV, Mayorov AYu, editors. [Standards of specialized diabetes care]. 11th ed. Moscow; 2023. Russian. Available from: https://webmed.irkutsk.ru/doc/pdf/algosd.pdf.Дедов ИИ, Шестакова МВ, Майоров АЮ, ред. Алгоритмы специализированной медицинской помощи больным сахарным диабетом. Вып. 11. М.; 2023. Доступно на: https://webmed.irkutsk.ru/doc/pdf/algosd.pdf.Alexopoulou O, Bex M, Kamenicky P, Mvoula AB, Chanson P, Maiter D. Prevalence and risk factors of impaired glucose tolerance and diabetes mellitus at diagnosis of acromegaly: a study in 148 patients. Pituitary. 2014;17(1):81–89. doi: 10.1007/s11102-013-0471-7.Dal J, Feldt-Rasmussen U, Andersen M, Kristensen LØ, Laurberg P, Pedersen L, Dekkers OM, Sørensen HT, Jørgensen JO. Acromegaly incidence, prevalence, complications and long-term prognosis: a nationwide cohort study. Eur J Endocrinol. 2016;175(3):181–190. doi: 10.1530/EJE-16-0117.Rosario PW. Frequency of acromegaly in adults with diabetes or glucose intolerance and estimated prevalence in the general population. Pituitary. 2011;14(3):217–221. doi: 10.1007/s11102-010-0281-0.Suda K, Fukuoka H, Iguchi G, Hirota Y, Nishizawa H, Bando H, Matsumoto R, Takahashi M, Sakaguchi K, Takahashi Y. The prevalence of acromegaly in hospitalized patients with type 2 diabetes. Endocr J. 2015;62(1):53–59. doi: 10.1507/endocrj.EJ14-0254.Dreval AV, Trigolosova IV, Misnikova IV, Kovalyova YA, Tishenina RS, Barsukov IA, Vinogradova AV, Wolffenbuttel BH. Prevalence of diabetes mellitus in patients with acromegaly. Endocr Connect. 2014;3(2):93–98. doi: 10.1530/EC-14-0021.Gordon DA, Hill FM, Ezrin C. Acromegaly: a review of 100 cases. Can Med Assoc J. 1962;87(21):1106–1109.Kreze A, Kreze-Spirova E, Mikulecky M. Risk factors for glucose intolerance in active acromegaly. Braz J Med Biol Res. 2001;34(11):1429–1433. doi: 10.1590/s0100-879x2001001100009.Fieffe S, Morange I, Petrossians P, Chanson P, Rohmer V, Cortet C, Borson-Chazot F, Brue T, Delemer B; French Acromegaly Registry. Diabetes in acromegaly, prevalence, risk factors, and evolution: data from the French Acromegaly Registry. Eur J Endocrinol. 2011;164(6):877–884. doi: 10.1530/EJE-10-1050.Vallette S, Ezzat S, Chik C, Ur E, Imran SA, Van Uum S, Rivera J, Caspar-Bell G, Serri O. Emerging trends in the diagnosis and treatment of acromegaly in Canada. Clin Endocrinol (Oxf). 2013;79(1):79–85. doi: 10.1111/cen.12112.Fukuda I, Hizuka N, Muraoka T, Kurimoto M, Yamakado Y, Takano K, Ichihara A. Clinical features and therapeutic outcomes of acromegaly during the recent 10 years in a single institution in Japan. Pituitary. 2014;17(1):90–95. doi: 10.1007/s11102-013-0472-6.Lesén E, Granfeldt D, Houchard A, Dinet J, Berthon A, Olsson DS, Björholt I, Johannsson G. Comorbidities, treatment patterns and cost-of-illness of acromegaly in Sweden: a register-linkage population-based study. Eur J Endocrinol. 2017;176(2):203–212. doi: 10.1530/EJE-16-0623.Petrossians P, Daly AF, Natchev E, Maione L, Blijdorp K, Sahnoun-Fathallah M, Auriemma R, Diallo AM, Hulting AL, Ferone D, Hana V Jr, Filipponi S, Sievers C, Nogueira C, Fajardo-Montañana C, Carvalho D, Hana V, Stalla GK, Jaffrain-Réa ML, Delemer B, Colao A, Brue T, Neggers SJCMM, Zacharieva S, Chanson P, Beckers A. Acromegaly at diagnosis in 3173 patients from the Liège Acromegaly Survey (LAS) Database. Endocr Relat Cancer. 2017;24(10):505–518. doi: 10.1530/ERC-17-0253.González B, Vargas G, de Los Monteros ALE, Mendoza V, Mercado M. Persistence of Diabetes and Hypertension After Multimodal Treatment of Acromegaly. J Clin Endocrinol Metab. 2018;103(6):2369–2375. doi: 10.1210/jc.2018-00325.Gatto F, Trifirò G, Lapi F, Cocchiara F, Campana C, Dell'Aquila C, Ferrajolo C, Arvigo M, Cricelli C, Giusti M, Ferone D. Epidemiology of acromegaly in Italy: analysis from a large longitudinal primary care database. Endocrine. 2018;61(3):533–541. doi: 10.1007/s12020-018-1630-4.Li YL, Zhang S, Guo XP, Gao L, Lian W, Yao Y, Deng K, Wang RZ, Xing B. Correlation analysis between short-term insulin-like growth factor-I and glucose intolerance status after transsphenoidal adenomectomy in acromegalic patients: a large retrospective study from a single center in China. Arch Endocrinol Metab. 2019;63(2):157–166. doi: 10.20945/2359-3997000000118.Park KH, Lee EJ, Seo GH, Ku CR. Risk for Acromegaly-related Comorbidities by Sex in Korean Acromegaly. J Clin Endocrinol Metab. 2020;105(4):dgz317. doi: 10.1210/clinem/dgz317.AlMalki MH, Ahmad MM, Buhary BM, Aljawair R, Alyamani A, Alhozali A, Alshahrani A, Alzahrani S, Nasser T, Alzahrani W, Raef H, Aldawish M, Elkhzaimy A. Clinical features and therapeutic outcomes of patients with acromegaly in Saudi Arabia: a retrospective analysis. Hormones (Athens). 2020;19(3):377–383. doi: 10.1007/s42000-020-00191-0.Guo X, Wang K, Yu S, Gao L, Wang Z, Zhu H, Xing B, Zhang S, Dong D. Patient Characteristics, Diagnostic Delays, Treatment Patterns, Treatment Outcomes, Comorbidities, and Treatment Costs of Acromegaly in China: A Nationwide Study. Front Endocrinol (Lausanne). 2020;11:610519. doi: 10.3389/fendo.2020.610519.Matsubayashi K, Kawakami K. Prevalence, incidence, comorbidities, and treatment patterns among Japanese patients with acromegaly: a descriptive study using a nationwide claims database. Endocr J. 2020;67(10):997–1006. doi: 10.1507/endocrj.EJ20-0129.Berkmann S, Brun J, Schuetz P, Christ E, Mariani L, Mueller B. Prevalence and outcome of comorbidities associated with acromegaly. Acta Neurochir (Wien). 2021;163(11):3171–3180. doi: 10.1007/s00701-021-04846-8.Dedov II, Shestakova MV, Vikulova OK, Zheleznyakova AV, Isakov MA, Sazonova DV, Mokrysheva NG. [Diabetes mellitus in the Russian Federation: dynamics of epidemiological indicators according to the Federal Register of Diabetes Mellitus for the period 2010–2022]. Diabetes Mellitus. 2023;26(2):104–123. Russian. doi: 10.14341/DM13035.Дедов ИИ, Шестакова МВ, Викулова ОК, Железнякова АВ, Исаков МА, Сазонова ДВ, Мокрышева НГ. Сахарный диабет в Российской Федерации: динамика эпидемиологических показателей по данным Федерального регистра сахарного диабета за период 2010–2022 гг. Сахарный диабет. 2023;26(2):104–123. doi: 10.14341/DM13035.Yun SJ, Lee JK, Park SY, Chin SO. Descriptive Epidemiology and Survival Analysis of Acromegaly in Korea. J Korean Med Sci. 2021;36(23):e159. doi: 10.3346/jkms.2021.36.e159.Colao A, Grasso LFS, Di Cera M, Thompson-Leduc P, Cheng WY, Cheung HC, Duh MS, Neary MP, Pedroncelli AM, Maamari R, Pivonello R. Association between biochemical control and comorbidities in patients with acromegaly: an Italian longitudinal retrospective chart review study. J Endocrinol Invest. 2020;43(4):529–538. doi: 10.1007/s40618-019-01138-y.Tseng FY, Chen ST, Chen JF, Huang TS, Lin JD, Wang PW, Huey-Herng Sheu W, Chang TC; Acromegaly Registry Study Group. Correlations of clinical parameters with quality of life in patients with acromegaly: Taiwan Acromegaly Registry. J Formos Med Assoc. 2019;118(11):1488–1493. doi: 10.1016/j.jfma.2019.05.007.Ilovayskaya IA. [Optimization of the follow-up and treatment of patients with acromegaly with the SAGIT® tool]. Almanac of Clinical Medicine. 2022;50(4):274–280. Russian. doi: 10.18786/2072-0505-2022-50-042.Иловайская ИА. Оптимизация наблюдения и лечения пациентов с акромегалией при помощи инструмента САГИТ. Альманах клинической медицины. 2022;50(4):274–280. doi: 10.18786/2072-0505-2022-50-042.Giustina A, Bronstein MD, Chanson P, Petersenn S, Casanueva FF, Sert C, Houchard A, Melmed S. Staging and managing patients with acromegaly in clinical practice: baseline data from the SAGIT® validation study. Pituitary. 2019;22(5):476–487. doi: 10.1007/s11102-019-00977-5.Mazziotti G, Gola M, Bianchi A, Porcelli T, Giampietro A, Cimino V, Doga M, Gazzaruso C, De Marinis L, Giustina A. Influence of diabetes mellitus on vertebral fractures in men with acromegaly. Endocrine. 2011;40(1):102–108. doi: 10.1007/s12020-011-9486-xCheng S, Gomez K, Serri O, Chik C, Ezzat S. The role of diabetes in acromegaly associated neoplasia. PLoS One. 2015;10(5):e0127276. doi: 10.1371/journal.pone.0127276.Møller N, Jørgensen JO. Effects of growth hormone on glucose, lipid, and protein metabolism in human subjects. Endocr Rev. 2009;30(2):152–177. doi: 10.1210/er.2008-0027.Vijayakumar A, Novosyadlyy R, Wu Y, Yakar S, LeRoith D. Biological effects of growth hormone on carbohydrate and lipid metabolism. Growth Horm IGF Res. 2010;20(1):1–7. doi: 10.1016/j.ghir.2009.09.002.Shulman GI. Ectopic fat in insulin resistance, dyslipidemia, and cardiometabolic disease. N Engl J Med. 2014;371(12):1131–1141. doi: 10.1056/NEJMra1011035.Biagetti B, Aulinas A, Casteras A, Pérez-Hoyos S, Simó R. HOMA-IR in acromegaly: a systematic review and meta-analysis. Pituitary. 2021;24(2):146–158. doi: 10.1007/s11102-020-01092-6.Sun Q, Li X, Chen P, Chen L, Zhao X. The Beta-Cell Function and Glucose Profile of Newly Diagnosed Acromegalic Patients with Normal Glucose Tolerance. Int J Endocrinol. 2021;2021:3666692. doi: 10.1155/2021/3666692.Niculescu DA, Dusceac R, Caragheorgheopol A, Popescu N, Poiana C. Disposition Index in Active Acromegaly. Front Endocrinol (Lausanne). 2019;10:637. doi: 10.3389/fendo.2019.00637.Wasada T, Aoki K, Sato A, Katsumori K, Muto K, Tomonaga O, Yokoyama H, Iwasaki N, Babazono T, Takahashi C, Iwamoto Y, Omori Y, Hizuka N. Assessment of insulin resistance in acromegaly associated with diabetes mellitus before and after transsphenoidal adenomectomy. Endocr J. 1997;44(4):617–620. doi: 10.1507/endocrj.44.617.Ferraù F, Albani A, Ciresi A, Giordano C, Cannavò S. Diabetes Secondary to Acromegaly: Physiopathology, Clinical Features and Effects of Treatment. Front Endocrinol (Lausanne). 2018;9:358. doi: 10.3389/fendo.2018.00358.Moustaki M, Paschou SA, Xekouki P, Kotsa K, Peppa M, Psaltopoulou T, Kalantaridou S, Vryonidou A. Secondary diabetes mellitus in acromegaly. Endocrine. 2023;81(1):1–15. doi: 10.1007/s12020-023-03339-1.Shekhawat VS, Bhansali S, Dutta P, Mukherjee KK, Vaiphei K, Kochhar R, Sinha SK, Sachdeva N, Kurpad AV, Bhat K, Mudaliar S, Bhansali A. Glucose-dependent Insulinotropic Polypeptide (GIP) Resistance and β-cell Dysfunction Contribute to Hyperglycaemia in Acromegaly. Sci Rep. 2019;9(1):5646. doi: 10.1038/s41598-019-41887-7.Matchekhina LV, Belaia ZhE, Melnichenko GA, Shestakova MV. [Carbohydrate metabolism in patients with acromegaly and Itsenko-Cushing disease]. Terapevticheskii Arkhiv [Therapeutic Archive]. 2015;87(10):98–104. Russian. doi: 10.17116/terarkh2015871098-104.Мачехина ЛВ, Белая ЖЕ, Мельниченко ГА, Шестакова МВ. Углеводный обмен у пациентов с акромегалией и болезнью Иценко – Кушинга. Терапевтический архив. 2015;87(10):98–104.Zhulidova AY, Filimonova AY, Tverdova LV, Nikiforov AA, Uryasev OM, Dubinina II. [Polymorphic markers of the genes of diabetes mellitus in patients with acromegaly]. Modern Science: Actual Problems of Theory & Practice. Series of Natural and Technical Sciences. 2019;(11):154–159. Russian.Жулидова АЮ, Филимонова АЮ, Твердова ЛВ, Никифоров АА, Урясьев ОМ, Дубинина ИИ. Полиморфные маркеры генов сахарного диабета у больных акромегалией. Современная наука: актуальные проблемы теории и практики. Серия: Естественные и Технические Науки. 2019;(11):154–159.Turvey SJ, McPhillie MJ, Kearney MT, Muench SP, Simmons KJ, Fishwick CWG. Recent developments in the structural characterisation of the IR and IGF1R: implications for the design of IR-IGF1R hybrid receptor modulators. RSC Med Chem. 2022;13(4):360–374. doi: 10.1039/d1md00300c.Al-Samerria S, Radovick S. The Role of Insulin-like Growth Factor-1 (IGF-1) in the Control of Neuroendocrine Regulation of Growth. Cells. 2021;10(10):2664. doi: 10.3390/cells10102664.Mori K, Iwasaki Y, Kawasaki-Ogita Y, Honjo S, Hamamoto Y, Tatsuoka H, Fujimoto K, Ikeda H, Wada Y, Takahashi Y, Takahashi J, Koshiyama H. Improvement of insulin resistance following transsphenoidal surgery in patients with acromegaly: correlation with serum IGF-I levels. J Endocrinol Invest. 2013;36(10):853–859. doi: 10.3275/8964.Singla M, Kaur Saini J. Diabetes Mellitus of Pituitary Origin: A Case Report. touchREV Endocrinol. 2021;17(1):68–70. doi: 10.17925/EE.2021.17.1.68.Suda K, Matsumoto R, Fukuoka H, Iguchi G, Hirota Y, Nishizawa H, Bando H, Yoshida K, Odake Y, Takahashi M, Sakaguchi K, Ogawa W, Takahashi Y. The influence of type 2 diabetes on serum GH and IGF-I levels in hospitalized Japanese patients. Growth Horm IGF Res. 2016;29:4–10. doi: 10.1016/j.ghir.2016.03.002.Chisalita SI, Ludvigsson J. Insulin-Like Growth Factor-1 at Diagnosis and during Subsequent Years in Adolescents with Type 1 Diabetes. J Diabetes Res. 2018;2018:8623560. doi: 10.1155/2018/8623560.Sorkina EL, Chichkova VV, Sklyanik IA, Shestakova MV, Mel'nichenko GA, Barkan A. The role of glucose and insulin in the metabolic regulation of growth hormone secretion. Problems of Endocrinology. 2021;67(1):52–59. doi: 10.14341/probl12660.Соркина ЕЛ, Чичкова ВВ, Скляник ИА, Шестакова МВ, Мельниченко ГА, Баркан А. Роль глюкозы и инсулина в метаболической регуляции секреции гормона роста. Проблемы Эндокринологии. 2021;67(1):52–59. doi: 10.14341/probl12660.Astaf'eva LI, Kalinin PL, Kadashev BA. Modern diagnosis and postoperative monitoring of acromegaly patients at a neurosurgical clinic. Voprosy Neirokhirurgii [Neurosurgery Issue]. 2017;81(1):58–62. doi: 10.17116/neiro201780758-62.Астафьева ЛИ, Калинин ПЛ, Кадашев БА. Современная диагностика и послеоперационный мониторинг пациентов с акромегалией в условиях нейрохирургической клиники. Вопросы нейрохирургии. 2017;81(1):58–62.Lutsenko AS, Belaya ZE, Przhiyalkovskaya EG, Lapshina AM, Nikitin AG, Azizyan VN, Ivaschenko OV, Grigoriev AYu, Melnichenko GA. [Short-term and long-term remission after endoscopic transnasal adenomectomy in patients with acromegaly]. Problems of Endocrinology. 2022;68(6):67–75. Russian. doi: 10.14341/probl13192.Луценко АС, Белая ЖЕ, Пржиялковская ЕГ, Лапшина АМ, Никитин АГ, Азизян ВН, Иващенко ОВ, Григорьев АЮ, Мельниченко ГА. Оценка краткосрочной и долгосрочной ремиссии акромегалии после эндоскопической трансназальной аденомэктомии. Проблемы Эндокринологии. 2022;68(6):67–75. doi: 10.14341/probl13192.Tsiberkin AI, Tsoy UA, Cherebillo VYu, Polezhaev AV, Gussarova NV, Grineva EN. Evaluation of transsphenoidal adenomectomy outcomes in acromegaly using different remission criteria. Voprosy Neirokhirurgii [Neurosurgery Issue]. 2019;83(1):98–104. doi: 10.17116/neiro20198301198.Циберкин АИ, Цой УА, Черебилло ВЮ, Полежаев АВ, Гуссарова НВ, Гринева ЕН. Оценка результатов транссфеноидальной аденомэктомии при акромегалии с применением различных критериев ремиссии. Вопросы нейрохирургии. 2019;83(1):98–104.Braun M. The somatostatin receptor in human pancreatic β-cells. Vitam Horm. 2014;95:165–193. doi: 10.1016/B978-0-12-800174-5.00007-7.Giustina A, Mazziotti G, Maffezzoni F, Amoroso V, Berruti A. Investigational drugs targeting somatostatin receptors for treatment of acromegaly and neuroendocrine tumors. Expert Opin Investig Drugs. 2014;23(12):1619–1635. doi: 10.1517/13543784.2014.942728.Cozzolino A, Feola T, Simonelli I, Puliani G, Pozza C, Giannetta E, Gianfrilli D, Pasqualetti P, Lenzi A, Isidori AM. Somatostatin Analogs and Glucose Metabolism in Acromegaly: A Meta-analysis of Prospective Interventional Studies. J Clin Endocrinol Metab. 2018. doi: 10.1210/jc.2017-02566. Epub ahead of print.Dreval' AV, Trigolosova IV, Vinogradova AV, Ilovaĭskaia IA. [The prevalence of diabetes mellitus among the patients with acromegaly]. Problems of Endocrinology. 2012;58(3):9–11. Russian.Древаль АВ, Триголосова ИВ, Виноградова АВ, Иловайская ИА. Распространенность сахарного диабета среди больных акромегалией. Проблемы эндокринологии. 2012;58(3):9–11.Shen M, Wang M, He W, He M, Qiao N, Ma Z, Ye Z, Zhang Q, Zhang Y, Yang Y, Cai Y, ABuDuoReYi-Mu Y, Lu Y, Lu B, Shou X, Wang Y, Ye H, Li Y, Li S, Zhao Y, Cao X, Zhang Z. Impact of Long-Acting Somatostatin Analogues on Glucose Metabolism in Acromegaly: A Hospital-Based Study. Int J Endocrinol. 2018;2018:3015854. doi: 10.1155/2018/3015854.Colao A, Auriemma RS, Savastano S, Galdiero M, Grasso LF, Lombardi G, Pivonello R. Glucose tolerance and somatostatin analog treatment in acromegaly: a 12-month study. J Clin Endocrinol Metab. 2009;94(8):2907–2914. doi: 10.1210/jc.2008-2627.Caron PJ, Petersenn S, Houchard A, Sert C, Bevan JS; PRIMARYS Study Group. Glucose and lipid levels with lanreotide autogel 120 mg in treatment-naïve patients with acromegaly: data from the PRIMARYS study. Clin Endocrinol (Oxf). 2017;86(4):541–551. doi: 10.1111/cen.13285.Cappellani D, Urbani C, Sardella C, Scattina I, Marconcini G, Lupi I, Manetti L, Marcocci C, Bogazzi F. Diabetes mellitus induced by somatostatin analogue therapy is not permanent in acromegalic patients. Endocrinol Diabetes Metab. 2018;2(1):e00033. doi: 10.1002/edm2.33.Lopez Vicchi F, Luque GM, Brie B, Nogueira JP, Garcia Tornadu I, Becu-Villalobos D. Dopaminergic drugs in type 2 diabetes and glucose homeostasis. Pharmacol Res. 2016;109:74–80. doi: 10.1016/j.phrs.2015.12.029.Auriemma RS, De Alcubierre D, Pirchio R, Pivonello R, Colao A. Glucose Abnormalities Associated to Prolactin Secreting Pituitary Adenomas. Front Endocrinol (Lausanne). 2019;10:327. doi: 10.3389/fendo.2019.00327.Pirchio R, Auriemma RS, Montini ME, Vergura A, Pivonello R, Colao A. Control of acromegaly in more than 90% of patients after 10 years of pegvisomant therapy: an European referral centre real-life experience. J Endocrinol Invest. 2023;46(5):1027–1038. doi: 10.1007/s40618-022-01980-7.Barkan AL, Burman P, Clemmons DR, Drake WM, Gagel RF, Harris PE, Trainer PJ, van der Lely AJ, Vance ML. Glucose homeostasis and safety in patients with acromegaly converted from long-acting octreotide to pegvisomant. J Clin Endocrinol Metab. 2005;90(10):5684–5691. doi: 10.1210/jc.2005-0331.Bernabeu I, Pico A, Venegas E, Aller J, Alvarez-Escolá C, García-Arnés JA, Marazuela M, Jonsson P, Mir N, García Vargas M; Spanish ACROSTUDY Group. Safety of long-term treatment with Pegvisomant: analysis of Spanish patients included in global ACROSTUDY. Pituitary. 2016;19(2):127–137. doi: 10.1007/s11102-015-0691-0.Brue T, Lindberg A, Jan van der Lely A, Akerblad AC, Koltowska-Häggström M, Gomez R, Droste M, Hey-Hadavi J, Strasburger CJ, Camacho-Hübner C. Diabetes in patients with acromegaly treated with pegvisomant: observations from Acrostudy. Endocrine. 2019;63(3):563–572. doi: 10.1007/s12020-018-1792-0.Feola T, Cozzolino A, Simonelli I, Sbardella E, Pozza C, Giannetta E, Gianfrilli D, Pasqualetti P, Lenzi A, Isidori AM. Pegvisomant Improves Glucose Metabolism in Acromegaly: A Meta-Analysis of Prospective Interventional Studies. J Clin Endocrinol Metab. 2019;104(7):2892–2902. doi: 10.1210/jc.2018-02281.Giustina A, Barkan A, Beckers A, Biermasz N, Biller BMK, Boguszewski C, Bolanowski M, Bonert V, Bronstein MD, Casanueva FF, Clemmons D, Colao A, Ferone D, Fleseriu M, Frara S, Gadelha MR, Ghigo E, Gurnell M, Heaney AP, Ho K, Ioachimescu A, Katznelson L, Kelestimur F, Kopchick J, Krsek M, Lamberts S, Losa M, Luger A, Maffei P, Marazuela M, Mazziotti G, Mercado M, Mortini P, Neggers S, Pereira AM, Petersenn S, Puig-Domingo M, Salvatori R, Shimon I, Strasburger C, Tsagarakis S, van der Lely AJ, Wass J, Zatelli MC, Melmed S. A Consensus on the Diagnosis and Treatment of Acromegaly Comorbidities: An Update. J Clin Endocrinol Metab. 2020;105(4):dgz096. doi: 10.1210/clinem/dgz096.Bhattacharya S, Kalra S, Dutta D, Khandelwal D, Singla R. The Interplay Between Pituitary Health and Diabetes Mellitus – The Need for 'Hypophyseo-Vigilance'. Eur Endocrinol. 2020;16(1):25–31. doi: 10.17925/EE.2020.16.1.25.Vila G, Jørgensen JOL, Luger A, Stalla GK. Insulin Resistance in Patients With Acromegaly. Front Endocrinol (Lausanne). 2019;10:509. doi: 10.3389/fendo.2019.00509.Droste M, Domberg J, Buchfelder M, Mann K, Schwanke A, Stalla G, Strasburger CJ. Therapy of acromegalic patients exacerbated by concomitant type 2 diabetes requires higher pegvisomant doses to normalise IGF1 levels. Eur J Endocrinol. 2014;171(1):59–68. doi: 10.1530/EJE-13-0438.Baroni MG, Giorgino F, Pezzino V, Scaroni C, Avogaro A. Italian Society for the Study of Diabetes (SID)/Italian Endocrinological Society (SIE) guidelines on the treatment of hyperglycemia in Cushing's syndrome and acromegaly. J Endocrinol Invest. 2016;39(2):235–255. doi: 10.1007/s40618-015-0404-6.Störmann S, Schopohl J. Drug treatment strategies for secondary diabetes in patients with acromegaly. Expert Opin Pharmacother. 2020;21(15):1883–1895. doi: 10.1080/14656566.2020.1789098.Cambuli VM, Galdiero M, Mastinu M, Pigliaru F, Auriemma RS, Ciresi A, Pivonello R, Amato M, Giordano C, Mariotti S, Colao A, Baroni MG. Glycometabolic control in acromegalic patients with diabetes: a study of the effects of different treatments for growth hormone excess and for hyperglycemia. J Endocrinol Invest. 2012;35(2):154–159. doi: 10.3275/7685.Chen Y, Mushashi F, Son S, Bhatti P, Dummer T, Murphy RA. Diabetes medications and cancer risk associations: a systematic review and meta-analysis of evidence over the past 10 years. Sci Rep. 2023;13(1):11844. doi: 10.1038/s41598-023-38431-z.Albertelli M, Nazzari E, Dotto A, Grasso LF, Sciallero S, Pirchio R, Rebora A, Boschetti M, Pivonello R, Ricci Bitti S, Colao AAL, Ferone D. Possible protective role of metformin therapy on colonic polyps in acromegaly: an exploratory cross-sectional study. Eur J Endocrinol. 2021;184(3):419–425. doi: 10.1530/EJE-20-0795.Gradiser M, Matovinovic M, Vrkljan M. Decrease in growth hormone and insulin-like growth factor (IGF)-1 release and amelioration of acromegaly features after rosiglitazone treatment of type 2 diabetes mellitus a patient with acromegaly. Croat Med J. 2007;48(1):87–91.Watanabe A, Komine F, Nirei K, Tamura K, Nabe K, Aiba N, Kamoshida S, Otsuka M, Okubo H, Kanou M, Sawada S, Uchiyama T, Nakamura S, Arakawa Y. A case of secondary diabetes mellitus with acromegaly improved by pioglitazone. Diabet Med. 2004;21(9):1049–1050. doi: 10.1111/j.1464-5491.2004.01299.x.Heaney AP, Fernando M, Melmed S. PPAR-gamma receptor ligands: novel therapy for pituitary adenomas. J Clin Invest. 2003;111(9):1381–1388. doi: 10.1172/JCI16575.Zaina A, Grober Y, Abid A, Arad E, Golden E, Badarny S. Sodium glucose cotransporter 2 inhibitors treatment in acromegalic patients with diabetes – a case series and literature review. Endocrine. 2021;73(1):65–70. doi: 10.1007/s12020-021-02718-w.Quarella M, Walser D, Brändle M, Fournier JY, Bilz S. Rapid Onset of Diabetic Ketoacidosis After SGLT2 Inhibition in a Patient With Unrecognized Acromegaly. J Clin Endocrinol Metab. 2017;102(5):1451–1453. doi: 10.1210/jc.2017-00082.da Rocha AF, Pereira Junior PS, Calefi GS, Marquezine GF, Morimoto HK, Mazzuco TL, de Faria EC, Urbano MR, Carrilho AJF. Growth hormone directly favors hepatic ketogenesis in persons with prediabetes or type 2 diabetes mellitus treated with empagliflozin. Endocrine. 2021;73(2):325–330. doi: 10.1007/s12020-021-02730-0.Adnan Z. Sodium Glucose Co-transporter Inhibitors in Patients with Acromegaly and Diabetes. Trends Endocrinol Metab. 2019;30(2):77–79. doi: 10.1016/j.tem.2018.11.007.Davies MJ, Aroda VR, Collins BS, Gabbay RA, Green J, Maruthur NM, Rosas SE, Del Prato S, Mathieu C, Mingrone G, Rossing P, Tankova T, Tsapas A, Buse JB. Management of Hyperglycemia in Type 2 Diabetes, 2022. A Consensus Report by the American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD). Diabetes Care. 2022;45(11):2753–2786. doi: 10.2337/dci22-0034.