Оптимизация методов лечения пациентов с акромегалией за последнее десятилетие. Обзор последних рекомендаций 2021 г.
Демидова Т.Ю., Потешкин Ю.Е., Прохорова Я.Д. Оптимизация методов лечения пациентов с акромегалией за последнее десятилетие. Обзор последних рекомендаций 2021 г. FOCUS Эндокринология. 2021; 4: 8–14. DOI: 10.47407/ef2021.2.4.0043
Demidova T.Yu., Poteshkin Yu.Е., Prokhorova Ya.D. Optimization of methods for treatment of acromegalic patients in the past decades. Overview of recent guidelines issued in 2021. FOCUS Endocrinology. 2021; 4: 8–14. DOI: 10.47407/ef2021.2.4.0043
Акромегалия является социально-экономической проблемой в современном мире. Это тяжелое нейроэндокринное заболевание, которое приводит не только к развитию диспропорционального внешнего вида, но и к инвалидизации людей в результате развития тяжелых осложнений. На данный момент наиболее эффективным методом лечения акромегалии считается хирургическое лечение в объеме транс сфеноидального удаления аденомы гипофиза. В результате оперативного вмешательства можно добиться не только ослабления симптомов заболевания, но и развития стойкой ремиссии. Другими методами лечения акромегалии являются медикаментозный и лучевой. При медикаментозном методе лечения акромегалии используют три группы препаратов – аналоги соматостатина, антагонисты соматотропного гормона и агонисты дофамина. Лучевой метод терапии применяется преимущественно после операции для дополнительного воздействия на остатки опухоли. Во избежание развития серьезных осложнений акромегалии необходим частый биохимический контроль. Настоящая статья посвящена обзору обновленных клинических рекомендаций по лечению акромегалии.
Ключевые слова: акромегалия, транссфеноидальное удаление, медикаментозная терапия, лучевая терапия, биохимический контроль.
Ключевые слова: акромегалия, транссфеноидальное удаление, медикаментозная терапия, лучевая терапия, биохимический контроль.
1. Аметов А.С., Анциферов М.Б., Дедов И.И. и др. Национальные клинические рекомендации. Акромегалия: клиника, диагностика, дифференциальная диагностика, методы лечения. М., 2014.
[Ametov A.S., Antsiferov M.B., Dedov I.I. et al. National clinical guidelines. Acromegaly: clinic, diagnosis, differential diagnosis, treatment methods. Moscow, 2014 (In Russian)].
2. Пронин В.С., Потешкин Ю.Е., Гитель Е.П. и др. Современная стратегия ди-агностики и лечения соматотропином. М.: ГЭОТАР-Медиа, 2013.
[Pronin V.S., Poteshkin Yu.E., Gitel E.P. et al. Modern strategy for diagnosis and treatment with growth hormone. Moscow: GEOTAR-Media, 2013 (In Russian)].
3. Молитвословова Н.Н., Рожинская Л.Я., Мельниченко Г.А. Российский консенсус по диагностике, лечению и мониторингу акромегалии. Проблемы Эндокринологии. 2007; 53 (4): 37–41. DOI: 10.14341/probl 200753437-41
[Molitvoslovova N.N., Rozhinskaya L.Ya., Melnichenko G.A. Russian consensus on the diagnosis, treatment and monitoring of acromegaly. Problemy Endokri-nologii. 2007; 53 (4): 37–41. DOI: 10.14341/probl200753437-41 (In Russian)].
4. Белая Ж.Е., Голоунина О.О., Рожинская Л.Я. и др. Эпидемиология, клиниче-ские проявления и эффективность различных методов лечения акромега-лии по данным единого российского регистра опухолей гипоталамо-гипо-физарной системы. Проблемы Эндокринологии. 2020; 66 (1). DOI: 10.14341/probl10333
[Belaya Zh.E., Golounina OO, Rozhinskaya L.Ya. et al. Epidemiology, clinical man-ifestations and efficacy of various methods of treating acromegaly according to the data of the unified Russian register of tumors of the hypothalamic-pituitary system. Problemy Endokrinologii. 2020; 66 (1). DOI: 10.14341 / probl10333 (In Russian).]
5. Maione L, Chanson P. National acromegaly registries. Best Pract Res Clin En-docrinol Metab 2019; 33 (2): 101264. DOI:org/10.1016/j.beem. 2019.02.001
6. McDermott M. Endocrine secrets. 7th Edition. 2019; 4: 221–33.
7. Fleseriu M, Beverly MK Biller, Freda PU et al. A Pituitary Society update to acromegaly management guidelines. Pituitary 2021; 24 (1): 1–13. DOI: 10.1007/s11102-020-01091-7
8. Faje AT, Barkan AL. Basal, but not pulsatile, growth hormone secretion deter-mines the ambient circulating levels of insulin-like growth factor-I. J Clin En-docrinol Metab 2010; 95: 2486–91.
9. Katznelson L, Laws ER, Melmed Sh et al. Acromegaly: An Endocrine Society Clin-ical Practice Guideline. J Clin Endocrinol Metab. 2014; 99 (11): 3933–51. DOI: 10.1210/jc.2014-2700
10. Dimaraki EV, Jaffe CA, DeMott-Friberg R et al. Acromegaly with apparently nor-mal GH secretion: implications for diagnosis and follow-up. J Clin Endocrinol Metab 2002; 87: 3537–42.
11. Melmed S, Popovic V, Bidlingmaier M et al. Safety and efficacy of oral octreotide in acromegaly: results of a multicenter phase III trial. J Clin Endocrinol Metab 2015; 100 (4): 1699–1708.
12. Tuvia S, Pelled D, Marom K et al. A novel suspension formulation enhances intesti-nal absorption of macromolecules via transient and reversible transport mecha-nisms. Pharm Res 2014; 31 (8): 2010–21.
13. Tuvia S, Atsmon J, Teichman SL et al. Oral octreotide absorption in human sub-jects: comparable pharmacokinetics to parenteral octreotide and effective growth hormone suppression. J Clin Endocrinol Metab 2012; 97 (7): 2362–69.
14. Samson SL, Nachtigall LB, Fleseriu M et al. Maintenance of Acromegaly Control in Pa-tients Switching From Injectable Somatostatin Receptor Ligands to Oral Octreotide. J Clin Endocrinol Metab 2020; 105 (10): 3785–97. DOI: 10.1210/clinem/dgaa526.
15. Buchfelder M, Biller BMK, Webb SM et al. Long-term treatment with pegviso-mant: observations from 2090 acromegaly patients in ACROSTUDY. Eur J En-docrinol 2018; 179 (6): 419–27. DOI: 10.1530/EJE-18-0616
16. Brue T, Lindberg A, van der Lely А et al. Diabetes in patients with acromegaly treated with pegvisomant: observations from ACROSTUDY. Endocrine 2019; 63 (3): 563–72. DOI: 10.1007/s12020-018-1792-0
17. Tritos NA, Mattsson AF, Vila G et al. All-cause mortality in patients with acromegaly treated with pegvisomant: an ACROSTUDY analysis. Eur J Endocrinol 2020; 182 (3): 285–92.
18. Annamalai AK, Webb A, Kandasamy N et al. A comprehensive study of clinical, biochemical, radiological, vascular, cardiac, and sleep parameters in an unse-lected cohort of patients with acromegaly undergoing presurgical somatostatin receptor ligand therapy. J Clin Endocrinol Metab 2013; 98 (3): 1040–50.
19. Carmichael JD, Bonert VS, Nuño M et al. Acromegaly clinical trial methodology impact on reported biochemical efficacy rates of somatostatin receptor ligand treatments: a meta-analysis. J Clin Endocrinol Metab 2014; 99 (5): 1825–33.
20. Caron PJ, Bevan JS, Petersenn S et al. PRIMARYS Investigators. Tumor shrinkage with lanreotide autogel 120 mg as primary therapy in acromegaly: results of a prospective multicenter clinical trial. J Clin Endocrinol Metab 2014; 99 (4): 1282–90.
21. Trainer PJ, Drake WM, Katznelson L et al. Treatment of acromegaly with the growth hormone-receptor antagonist pegvisomant. N Engl J Med 2000; 342 (16): 1171–77.
22. Hutson RK, Trainer PJ, Besser GM et al. Long-term treatment of acromegaly with pegvisomant, a growth hormone receptor antagonist. Lancet 2001; 358 (9295): 1754–9.
23. Schreiber I, Buchfelder M, Droste M et al. Treatment of acromegaly with the GH receptor antagonist pegvisomant in clinical practice: safety and efficacy evaluation from the German Pegvisomant Observational Study. Eur J Endocrinol 2007; 156: 75–82.
24. Lely AJ, Biller BM, Brue T et al. Long-term safety of pegvisomant in patients with acromegaly: comprehensive review of 1288 subjects in ACROSTUDY. J Clin En-docrinol Metab 2012; 97 (5): 1589–97.
25. Freda PU, Gordon MB, Kelepouris N et al. Long-term treatment with pegvisomant as monotherapy in patients with acromegaly: experience from ACROSTUDY. En-docr Pract 2015; 21 (3): 264–74.
26. Grottoli S, Maffei P, Bogazzi F et al. ACROSTUDY: the Italian experience. En-docrine 2015; 48 (1): 334–41.
27. Droste M, Domberg J, Buchfelder M et al. Therapy of acromegalic patients exac-erbated by concomitant type 2 diabetes requires higher pegvisomant doses to normalise IGF1 levels. Eur J Endocrinol 2014; 171: 59–68.
28. Higham CE, Rowles S, Russell-Jones D et al. Pegvisomant improves insulin sensi-tivity and reduces overnight free fatty acid concentrations in patients with acromegaly. J Clin Endocrinol Metab 2009; 94 (7): 2459–63.
29. Lindberg-Larsen R, Moller N, Schmitz O et al. The impact of pegvisomant treat-ment on substrate metabolism and insulin sensitivity in patients with acromegaly. J Clin Endocrinol Metab 2007; 92 (5): 1724–8.
30. Urbani C, Sardella C, Calevro A et al. Effects of medical therapies for acromegaly on glucose metabolism. Eur J Endocrinol 2013; 169: 99–108.
31. Neggers SJ, Franck SE, Dallenga AH et al. Long-term efficacy and safety of pegvi-somant in combination with long-acting somatostatin analogs in acromegaly. J Clin Endocrinol Metab 2014; 99 (10): 3644–52.
32. Neggers SJ, Janssen JA, Feelders RA. Long-term efficacy and safety of combined treatment of somatostatin analogs and pegvisomant in acromegaly. J Clin En-docrinol Metab 2007; 92 (12): 4598–601.
33. Colao A, Bronstein MD, Freda P et al. Pasireotide versus octreotide in acromegaly: a head-to-head superiority study. J Clin Endocrinol Metab 2014; 99 (3): 791–9.
34. Gadelha 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): 875–84.
35. Trainer PJ, Drake WM, Katznelson L et al. Treatment of acromegaly with the growth hormone-receptor antagonist pegvisomant. N Engl J Med 2000; 342 (16): 1171–7.
36. Muhammad A, Coopmans EC, Delhanty P JD et al. Efficacy and safety of switching to pasireotide in acromegaly patients controlled with pegvisomant and somato-statin analogues: PAPE extension study. Eur J Endocrinol 2018; 179 (5): 269–77. DOI:org/10.1530/EJE-18-0353
37. Muhammad A, Delhanty PJD, Haitsma IK, Janssen J et al. Efficacy and safety of switching to pasireotide in patients with acromegaly controlled with pegviso-mant and first-generation somatostatin analogues (PAPE study) J Clin En-docrinol Metab 2018; 103 (2): 586–95. DOI: 10.1210/jc.2017-02017
38. Schöfl C, Franz H, Grussendorf M et al. Long-term results in patients with acromegaly: an analysis of 1344 patients from the German register of acromegaly. Eur J Endocrinol 2013; 39–47. DOI: 10.1530/EJE-12-0602
39. Diallo AM, Colin P, Liter CF et al. Long-term results of fractional stereotactic ra-diation therapy as a third-line treatment for acromegaly. Endocrine 2015; 741–
8. DOI:org/10.1007/s12020-015-0610-1
40. Melmed S, Kolao A, Barkan A et al. Guidelines for managing acromegaly: an up-date. J Clin Endocrinol Metab 2009; 1509–17. DOI: 10.1210/jc.2008-2421
41. Katznelson L, Lawes ER Molitch ME et al. Acromegaly: Clinical Practice Guide-lines for the Endocrine Society. J Clin Endocrinol Metab 2014; 3933–51. DOI:org/10.1210/jc.2014-2700
42. Melmed S, Bronstein MD, Chanson R et al. Consensus Statement for Treatment Outcomes for Acromegaly. Nature Reviews. Endocrinol 2018: 552–61. DOI: 10.1038/s41574-018-0058-5
43. Graffeo ChS, Donegan D, Erickson D et al. The Impact of Insulin-Like Growth Fac-tor Index and Biologically Effective Dose on Outcomes After Stereotactic Radio-surgery for Acromegaly: Cohort Study. Neurosurgery 2020; 87 (3): 538–46.
44. Knappe UJ, Petroff D, Quinkler M et al. Fractionated radiotherapy and radio-surgery in acromegaly: analysis of 352 patients from the German Acromegaly Registry. Eur J Endocrinol 2020; 182 (3): 275–84. DOI:org/10.1530/EJE-19-0784
[Ametov A.S., Antsiferov M.B., Dedov I.I. et al. National clinical guidelines. Acromegaly: clinic, diagnosis, differential diagnosis, treatment methods. Moscow, 2014 (In Russian)].
2. Пронин В.С., Потешкин Ю.Е., Гитель Е.П. и др. Современная стратегия ди-агностики и лечения соматотропином. М.: ГЭОТАР-Медиа, 2013.
[Pronin V.S., Poteshkin Yu.E., Gitel E.P. et al. Modern strategy for diagnosis and treatment with growth hormone. Moscow: GEOTAR-Media, 2013 (In Russian)].
3. Молитвословова Н.Н., Рожинская Л.Я., Мельниченко Г.А. Российский консенсус по диагностике, лечению и мониторингу акромегалии. Проблемы Эндокринологии. 2007; 53 (4): 37–41. DOI: 10.14341/probl 200753437-41
[Molitvoslovova N.N., Rozhinskaya L.Ya., Melnichenko G.A. Russian consensus on the diagnosis, treatment and monitoring of acromegaly. Problemy Endokri-nologii. 2007; 53 (4): 37–41. DOI: 10.14341/probl200753437-41 (In Russian)].
4. Белая Ж.Е., Голоунина О.О., Рожинская Л.Я. и др. Эпидемиология, клиниче-ские проявления и эффективность различных методов лечения акромега-лии по данным единого российского регистра опухолей гипоталамо-гипо-физарной системы. Проблемы Эндокринологии. 2020; 66 (1). DOI: 10.14341/probl10333
[Belaya Zh.E., Golounina OO, Rozhinskaya L.Ya. et al. Epidemiology, clinical man-ifestations and efficacy of various methods of treating acromegaly according to the data of the unified Russian register of tumors of the hypothalamic-pituitary system. Problemy Endokrinologii. 2020; 66 (1). DOI: 10.14341 / probl10333 (In Russian).]
5. Maione L, Chanson P. National acromegaly registries. Best Pract Res Clin En-docrinol Metab 2019; 33 (2): 101264. DOI:org/10.1016/j.beem. 2019.02.001
6. McDermott M. Endocrine secrets. 7th Edition. 2019; 4: 221–33.
7. Fleseriu M, Beverly MK Biller, Freda PU et al. A Pituitary Society update to acromegaly management guidelines. Pituitary 2021; 24 (1): 1–13. DOI: 10.1007/s11102-020-01091-7
8. Faje AT, Barkan AL. Basal, but not pulsatile, growth hormone secretion deter-mines the ambient circulating levels of insulin-like growth factor-I. J Clin En-docrinol Metab 2010; 95: 2486–91.
9. Katznelson L, Laws ER, Melmed Sh et al. Acromegaly: An Endocrine Society Clin-ical Practice Guideline. J Clin Endocrinol Metab. 2014; 99 (11): 3933–51. DOI: 10.1210/jc.2014-2700
10. Dimaraki EV, Jaffe CA, DeMott-Friberg R et al. Acromegaly with apparently nor-mal GH secretion: implications for diagnosis and follow-up. J Clin Endocrinol Metab 2002; 87: 3537–42.
11. Melmed S, Popovic V, Bidlingmaier M et al. Safety and efficacy of oral octreotide in acromegaly: results of a multicenter phase III trial. J Clin Endocrinol Metab 2015; 100 (4): 1699–1708.
12. Tuvia S, Pelled D, Marom K et al. A novel suspension formulation enhances intesti-nal absorption of macromolecules via transient and reversible transport mecha-nisms. Pharm Res 2014; 31 (8): 2010–21.
13. Tuvia S, Atsmon J, Teichman SL et al. Oral octreotide absorption in human sub-jects: comparable pharmacokinetics to parenteral octreotide and effective growth hormone suppression. J Clin Endocrinol Metab 2012; 97 (7): 2362–69.
14. Samson SL, Nachtigall LB, Fleseriu M et al. Maintenance of Acromegaly Control in Pa-tients Switching From Injectable Somatostatin Receptor Ligands to Oral Octreotide. J Clin Endocrinol Metab 2020; 105 (10): 3785–97. DOI: 10.1210/clinem/dgaa526.
15. Buchfelder M, Biller BMK, Webb SM et al. Long-term treatment with pegviso-mant: observations from 2090 acromegaly patients in ACROSTUDY. Eur J En-docrinol 2018; 179 (6): 419–27. DOI: 10.1530/EJE-18-0616
16. Brue T, Lindberg A, van der Lely А et al. Diabetes in patients with acromegaly treated with pegvisomant: observations from ACROSTUDY. Endocrine 2019; 63 (3): 563–72. DOI: 10.1007/s12020-018-1792-0
17. Tritos NA, Mattsson AF, Vila G et al. All-cause mortality in patients with acromegaly treated with pegvisomant: an ACROSTUDY analysis. Eur J Endocrinol 2020; 182 (3): 285–92.
18. Annamalai AK, Webb A, Kandasamy N et al. A comprehensive study of clinical, biochemical, radiological, vascular, cardiac, and sleep parameters in an unse-lected cohort of patients with acromegaly undergoing presurgical somatostatin receptor ligand therapy. J Clin Endocrinol Metab 2013; 98 (3): 1040–50.
19. Carmichael JD, Bonert VS, Nuño M et al. Acromegaly clinical trial methodology impact on reported biochemical efficacy rates of somatostatin receptor ligand treatments: a meta-analysis. J Clin Endocrinol Metab 2014; 99 (5): 1825–33.
20. Caron PJ, Bevan JS, Petersenn S et al. PRIMARYS Investigators. Tumor shrinkage with lanreotide autogel 120 mg as primary therapy in acromegaly: results of a prospective multicenter clinical trial. J Clin Endocrinol Metab 2014; 99 (4): 1282–90.
21. Trainer PJ, Drake WM, Katznelson L et al. Treatment of acromegaly with the growth hormone-receptor antagonist pegvisomant. N Engl J Med 2000; 342 (16): 1171–77.
22. Hutson RK, Trainer PJ, Besser GM et al. Long-term treatment of acromegaly with pegvisomant, a growth hormone receptor antagonist. Lancet 2001; 358 (9295): 1754–9.
23. Schreiber I, Buchfelder M, Droste M et al. Treatment of acromegaly with the GH receptor antagonist pegvisomant in clinical practice: safety and efficacy evaluation from the German Pegvisomant Observational Study. Eur J Endocrinol 2007; 156: 75–82.
24. Lely AJ, Biller BM, Brue T et al. Long-term safety of pegvisomant in patients with acromegaly: comprehensive review of 1288 subjects in ACROSTUDY. J Clin En-docrinol Metab 2012; 97 (5): 1589–97.
25. Freda PU, Gordon MB, Kelepouris N et al. Long-term treatment with pegvisomant as monotherapy in patients with acromegaly: experience from ACROSTUDY. En-docr Pract 2015; 21 (3): 264–74.
26. Grottoli S, Maffei P, Bogazzi F et al. ACROSTUDY: the Italian experience. En-docrine 2015; 48 (1): 334–41.
27. Droste M, Domberg J, Buchfelder M et al. Therapy of acromegalic patients exac-erbated by concomitant type 2 diabetes requires higher pegvisomant doses to normalise IGF1 levels. Eur J Endocrinol 2014; 171: 59–68.
28. Higham CE, Rowles S, Russell-Jones D et al. Pegvisomant improves insulin sensi-tivity and reduces overnight free fatty acid concentrations in patients with acromegaly. J Clin Endocrinol Metab 2009; 94 (7): 2459–63.
29. Lindberg-Larsen R, Moller N, Schmitz O et al. The impact of pegvisomant treat-ment on substrate metabolism and insulin sensitivity in patients with acromegaly. J Clin Endocrinol Metab 2007; 92 (5): 1724–8.
30. Urbani C, Sardella C, Calevro A et al. Effects of medical therapies for acromegaly on glucose metabolism. Eur J Endocrinol 2013; 169: 99–108.
31. Neggers SJ, Franck SE, Dallenga AH et al. Long-term efficacy and safety of pegvi-somant in combination with long-acting somatostatin analogs in acromegaly. J Clin Endocrinol Metab 2014; 99 (10): 3644–52.
32. Neggers SJ, Janssen JA, Feelders RA. Long-term efficacy and safety of combined treatment of somatostatin analogs and pegvisomant in acromegaly. J Clin En-docrinol Metab 2007; 92 (12): 4598–601.
33. Colao A, Bronstein MD, Freda P et al. Pasireotide versus octreotide in acromegaly: a head-to-head superiority study. J Clin Endocrinol Metab 2014; 99 (3): 791–9.
34. Gadelha 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): 875–84.
35. Trainer PJ, Drake WM, Katznelson L et al. Treatment of acromegaly with the growth hormone-receptor antagonist pegvisomant. N Engl J Med 2000; 342 (16): 1171–7.
36. Muhammad A, Coopmans EC, Delhanty P JD et al. Efficacy and safety of switching to pasireotide in acromegaly patients controlled with pegvisomant and somato-statin analogues: PAPE extension study. Eur J Endocrinol 2018; 179 (5): 269–77. DOI:org/10.1530/EJE-18-0353
37. Muhammad A, Delhanty PJD, Haitsma IK, Janssen J et al. Efficacy and safety of switching to pasireotide in patients with acromegaly controlled with pegviso-mant and first-generation somatostatin analogues (PAPE study) J Clin En-docrinol Metab 2018; 103 (2): 586–95. DOI: 10.1210/jc.2017-02017
38. Schöfl C, Franz H, Grussendorf M et al. Long-term results in patients with acromegaly: an analysis of 1344 patients from the German register of acromegaly. Eur J Endocrinol 2013; 39–47. DOI: 10.1530/EJE-12-0602
39. Diallo AM, Colin P, Liter CF et al. Long-term results of fractional stereotactic ra-diation therapy as a third-line treatment for acromegaly. Endocrine 2015; 741–
8. DOI:org/10.1007/s12020-015-0610-1
40. Melmed S, Kolao A, Barkan A et al. Guidelines for managing acromegaly: an up-date. J Clin Endocrinol Metab 2009; 1509–17. DOI: 10.1210/jc.2008-2421
41. Katznelson L, Lawes ER Molitch ME et al. Acromegaly: Clinical Practice Guide-lines for the Endocrine Society. J Clin Endocrinol Metab 2014; 3933–51. DOI:org/10.1210/jc.2014-2700
42. Melmed S, Bronstein MD, Chanson R et al. Consensus Statement for Treatment Outcomes for Acromegaly. Nature Reviews. Endocrinol 2018: 552–61. DOI: 10.1038/s41574-018-0058-5
43. Graffeo ChS, Donegan D, Erickson D et al. The Impact of Insulin-Like Growth Fac-tor Index and Biologically Effective Dose on Outcomes After Stereotactic Radio-surgery for Acromegaly: Cohort Study. Neurosurgery 2020; 87 (3): 538–46.
44. Knappe UJ, Petroff D, Quinkler M et al. Fractionated radiotherapy and radio-surgery in acromegaly: analysis of 352 patients from the German Acromegaly Registry. Eur J Endocrinol 2020; 182 (3): 275–84. DOI:org/10.1530/EJE-19-0784