Difficult patient with acromegaly: expanding horizons of opportunities


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Abstract

Acromegaly is a chronic neuroendocrine disease that affect the quality of life and its duration. Current treatments for acromegaly include neurosurgical intervention, drug therapy, and radiation therapy. First-line medications are first-generation somatostatin analogues (SSA) that are used after surgery and/or irradiation, and have also shown their effectiveness as primary therapy. A multicenter open-label phase 3b study has demonstrated the effectiveness of lanreotide Autogel in the treatment of 90 primary patients with acromegaly. Nevertheless, even after the combined use of the above treatment methods, up to 30-40% of patients with acromegaly remain without biochemical control of the disease. Among the various ways of overcoming resistance to SSA, the patient can be switched to therapy with pegvisomant, a selective growth hormone (GH) antagonist. The drug binds selectively to GH receptors on cell surfaces, inhibits the interaction of endogenous GH with its receptor, and blocks the intracellular transduction of its biological signal, which is manifested by a significant decrease in the insulin-like growth factor 1 level and a significant decrease in the clinical symptoms of acromegaly. The drug can be used in resistance to first-generation SAA, because its effectiveness does not depend on the histopathomorphological properties of somatotropinoma. Another advantage of pegvisomant is the possibility of its use in the progression of disorders of carbohydrate metabolism during therapy with SSA. The appearance of drug pegvisomant, registered in the Russian Federation in 2018 for the treatment of acromegaly in clinical practice, opens up new therapeutic possibilities for difficult patients with acromegaly

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About the authors

Irena A. Ilovaiskaya

M.F. Vladimirsky Moscow Regional Research and Clinical Institute; A.I. Yevdokimov Moscow State University of Medicine and Dentistry

Email: irena.ilov@yandex.ru
MD, Associate Professor at the Department of Outpatient Therapy, Faculty of Medicine; Senior Researcher at the Department of Therapeutic Endocrinology

References

  1. Dekkers O.M., Biermasz N.R., Pereira A.M., et al. Mortality in acromegaly: a metaanalysis. J. Clin Endocrinol Metab. 2008;3:61-7.
  2. Reid T.J., et al. IGF-1 levels across the spectrum of normal to elevated in acromegaly: relationship to insulin sensitivity, markers of cardiovascular risk and body composition. Pituit. 2015;18:808-19.
  3. Mercado M., et al. Successful mortality reduction and control of comorbidities in patients with acromegaly followed at a highly specialized multidisciplinary clinic. J. Clin Endocrinol Metab. 2014;99:4438-46.
  4. Giustina A., et al. A consensus on criteria for cure of acromegaly. J. Clin. Endocrinol. Metab. 2010;95:3141-48. doi: 10.1210/jc.2009-2670.
  5. Holdaway I.M., et al. A meta-analysis of the effect of lowering serum levels of GH and IGF-I on mortality in acromegaly Eur J. Endocrinol. 2008;159:89-95. doi: 10.1530/EJE-08-0267.
  6. Mercado M., et al. Successful mortality reduction and control of comorbidities in patients with acromegaly followed at a highly specialized multidisciplinary clinic. J. Clin Endocrinol Metab. 2014;99:4438-46.
  7. Phan K., Xu J., Reddy R., et al. Endoscopic endonasal versus microsurgical transphenoidal approach for growth hormone-secreting pituitary adenomas - systematic review and meta-analysis. Word Neurosurg. 2016;(Suppl.): 1878-87.
  8. Starnoni D., Daniel R.T., Marino L., et al. Surgical treatment of acromegaly according to the 2010 remission criteria: systematic review and meta-analysis. Acta Neurochir. (Wien). 2016;158(11):2109-21.
  9. Babu H., et al. Long- term endocrine outcomes following endoscopic endonasal transsphenoidal surgery for acromegaly and associated prognostic factors. Neurosurg. 2017;81:357-66.
  10. Starke R.M., et al. Endoscopic versus microsurgical transsphenoidal surgery for acromegaly: outcomes in a concurrent series of patients using modern criteria for remission. J. Clin Endocrinol Metab. 2013;98:3190-98.
  11. Clemmons D.R. Consensus statement on the standardization and evaluation of growth hormone and insulin- like growth factor assays. Clin Chem. 2011;57:555-59.
  12. Arafat A.M., et al. Growth hormone response during oral glucose tolerance test: the impact of assay method on the estimation of reference values in patients with acromegaly and in healthy controls, and the role of gender, age, and body mass index. J. Clin Endocrinol Metab. 2008;93:1254-62.
  13. Abu Dabrh A.M., Asi N., Farah W.H., et al. Radiotherapy versus radiosurgery in treating patients with acromegaly: a systematic review and meta-anaiysis. Endocr Pract. 2015;21(8):943-56. doi: 10.4158/EP14574.OR.
  14. Verheist J.A., Pedronceiii A.M., Abs R., et ai. Siow-reiease ianreotide in the treatment of acromegaiy: a study in 66 patients. Eur J. Endocrinoi. 2000;143:577-84.
  15. Freda PU., Katzneison L., van der Leiy A.J., et ai. long-acting somatostatin anaiog therapy of acromegaiy: a meta-anaiysis. J. Ciin Endocrinoi Metab. 2005;90(8):4465-73.
  16. Молитвословова Н.Н. Роль длительно действующего аналога соматостатина, Соматулина, в лечении акромегалии. Фарматека. 2005;12.
  17. Coiao A., Auriemma R.S., Pivoneiio R., et ai. Interpreting biochemicai controi response rates with first-generation somatostatin anaiogues in acromegaiy. Pituit. 2016;19(3):235-47. doi: 10.1007/s11102-015-0684-z PRIMARYS.
  18. Katzneison L., Laws E.R., Meimed S., et ai. Acromegaiy: an Endocrine Society ciinicai practice guideiine. J. Ciin Endocrinoi Metab. 2014;99(11):3933-51. doi: 10.1210/jc.2014-2700.
  19. Caron PJ., Bevan J.S., Petersenn S., et ai. Effects of ianreotide Autogei primary therapy on symptoms and quaiity-of-iife in acromegaiy: data from the PRIMARYS Study. Pituit. 2016;19(2):149-57. doi: 10.1007/s11102-015-0693-y.
  20. Caron PJ., Bevan J.S., Petersenn S., et ai. Tumor Shrinkage with Lanreotide Autogei 120 mg as Primary Therapy in Acromegaiy: Resuits of a Prospective Muiticenter Ciinicai Triai. J. Ciin Endocrinoi Metab. 2014;99(4):1282-90. doi: 10.1210/jc.2013-3318.
  21. Goia M., Bonadonna S., Mazziotti G., et ai. Resistance to somatostatin anaiogs in acromegaiy: an evoiving concept? J. Endocrinoi Invest. 2006;29(1):86-93. doi: 10.1007/BF03349183.
  22. Coiao A., Auriemma R.S., Lombardi G., Pivoneiio R. Resistance to somatostatin anaiogues in acromegaiy. Endocr Rev. 2011;32(2):247-71. doi: 10.1210/er.2010-0002.
  23. Sandret L., Maison P., Chanson P. Piace of cabergoiine in acromegaiy: a meta-anaiysis. J. Ciin Endocrinoi Metab. 2011;96(5):1327-35. doi: 10.1210/jc.2010-2443.
  24. Kuhn E., Chanson P. Cabergoiine in acromegaiy. Pituit. 2017;20(1):121-28. Doi: 10.1007/ s11102-016-0782-6.
  25. Gadeiha M.R., Wiidemberg L.E., Bronstein M.D., et al. Somatostatin receptor ligands in the treatment of acromegaly. Pituit. 2017;20(1):100-8. doi: 10.1007/s11102-017-0791-0.
  26. Stewart PM. Pegvisomant: an advance in clinical efficacy in acromegaly. Eur J. Endocrinol. 2003;148(2):27-32. Doi: 10.1530/ eje.0.148s027.
  27. van der Lely A.J., Hutson R.K., Trainer PJ., et al. Long-term treatment of acromegaly with pegvisomant, a growth hormone receptor antagonist. Lancet. 2001;358(9295):1754-59. doi: 10.1016/S0140-6736(01)06844-1.
  28. Trainer PJ., Drake W.M., Katznelson L., et al. Treatment of acromegaly with the growth hormone-receptor antagonist pegvisomant. N. Engl J. Med. 2000;342(16):1171-77. doi: 10.1056/NEJM200004203421604.
  29. van der Lely A.J., Biller B.M.K., 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):1589-97. doi: 10.1210/jc.2011-2508.
  30. Alexopoulou O., et al. Prevalence and risk factors of impaired glucose tolerance and diabetes mellitus at diagnosis of acromegaly: a study in 148 patients. Pituit. 2014;17:81-9. doi: 10.1007/s11102-013-0471-7.
  31. Arosio M., et al. Predictors of morbidity and mortality in acromegaly: an Italian survey. Eur J. Endocrinol. 2012;167:189-98. Doi: 10.1530/ EJE-12-0084.
  32. Dal J., et al. Acromegaly incidence, prevalence, complications and long-term prognosis: a nationwide cohort study. Eur J. Endocrinol. 2016;175:181-90. doi: 10.1530/EJE-16-0117.
  33. Dreval A.V., et al. Prevalence of diabetes mellitus in patients with acromegaly. Endocr. Connect. 2014;3:93-8. doi: 10.1530/EC-14-0021.
  34. Mestron A., et al. Epidemiology, clinical characteristics, outcome, morbidity and mortality in acromegaly based on the Spanish Acromegaly Registry (Registro Espanol de Acromegalia, REA). Eur J. Endocrinol. 2004;151:439-46.
  35. Parkinson C., et al. Gender and age influence the relationship between serum GH and IGF-I in patients with acromegaly Clin Endocrinol. 2002;57(1):59-64. doi: 10.1046/j1365-2265.2002.01560.x.
  36. Baroni, et al. Italian society of the study of diabetes/Italian Endocrinological Society guidelines on the treatment of hyperglycemia on Cushing's syndrome and acromegaly. J. Endocrinol Invest. 2016;39:235-55.
  37. Caron PJ. Glucose and lipid levels with lanreotide autogel 120 mg in treatment-naive patients with acromegaly: data from the PRIMARYS study. Clin Endocrinol. 2016. doi: 10.1111/cen.13285.
  38. Melmed S., et al. A Consensus Statement on acromegaly therapeutic outcomes. Nat. Rev. Endocrinol. 2018;14(9):552-61. Doi: 10.1038/ s41574-018-0058-5.
  39. Barkan A.L., Burman P., Clemmons D.R., et al. Glucose homeostasis and safety in patients with acromegaly converted from long-acting octreotide to pegvisomant. J. Clin Endocrinol Metab. 2005;90:5684-91. doi: 10.1210/jc.2005-0331.
  40. Drake W.M., Rowles S.V, Roberts M.E., al. Insulin sensitivity and glucose tolerance improve in patients with acromegaly converted from depot octreotide to pegvisomant. Eur J Endocrinol. 2003;149:521 27. doi: 10.1530/eje.0.1490521
  41. Brue T., 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.
  42. Droste 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. Eur J. Endocrinol. 2014;171:59-68. doi: 10.1530/EJE-13-0438.
  43. Giustina A., Arnaldi G., Bogazzi F., et al. Pegvisomant in acromegaly: an update. J. Endocrinol Invest. 2017;40:577-89. doi: 10.1007/s40618-017-0614-1.
  44. Boguszewski C.L., Huayllas M.KP, Vilar L., et al. Brazilian multicenter study on pegvisomant treatment in acromegaly. Arch Endocrinol Metab. 2019;63(4):328-36. doi: 10.20945/2359 3997000000159.
  45. Basavilbaso N.X.G., et al. Pegvisomant in acromegaly: a multicenter real-life study in Argentina. Arch Endocrinol Metab. 2019;63(4):320-27. doi: 10.20945/2359 3997000000160.
  46. Franck S.E., Muhammad A., van der Lely A.J., Neggers S.J. Combined treatment of somatostatin analogues with pegvisomant in acromegaly. Endocrine. 2016;52(2):206-13. Doi: 10.1007/ s12020-015-0810-8.
  47. Puig-Domingo M., Soto A., Venegas E., et al. ACROCOMB study group. Use of lanreotide in combination with cabergoline or pegvisomant in patients with acromegaly in the clinical practice: The ACROCOMB study. Endocrinol Nutr. 2016;63(8):397-408. Doi: 10.1016/j. endonu.2016.05.010.

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