Discordant parameters of insulin-like growth factor 1 and growth hormone in the diagnosis and monitoring of acromegaly
https://doi.org/10.14341/probl12791
Abstract
Acromegaly is a rare endocrine disorder associated with multiple complications and increased mortality. Timely diagnosis and adequate treatment can bring the life expectancy of patients with acromegaly closer to the general population level. The tests for the diagnosis of acromegaly are measurement of both serum GH, and GH after oral glucose administration; serum insulin-like growth factor-1 (IGF-1). However, in clinical practice, up to 39% of patients with discordant results are found. The patients with discordant GH and IGF-1levels, are the most difficult to manage. This review discusses the prevalence of discordant GH and IGF-1 outcomes in patients with acromegaly; factors causing this discrepancy; the impact of hormone levels on treatment outcomes. Although endocrinologists are used to dealing with this discrepancy in clinical practice for many years, discordant patients’outcome remains uncertain and undefined The optimal treatment should be individually tailored for each patient, taking into account all clinical parameters.
About the Authors
E. E. SakhnovaRussian Federation
Ekaterina E. Sakhnova, MD
11 Dm. Ulyanova street, 117292 Moscow
E. G. Przhiyalkovskaya
Russian Federation
Elena G. Przhiyalkovskaya, MD, PhD
Moscow
Zh. E. Belaya
Russian Federation
Zhanna E. Belaya, MD, PhD, Professor
Moscow
G. A. Melnichenko
Russian Federation
Galina A. Melnichenko, MD, PhD, acad.
Moscow
References
1. Lavrentaki A, Paluzzi A, Wass JA, et. al. Epidemiology of acromegaly: review of population studies. Pituitary. 2017;20(1):4-9. https://doi.org/10.1007/s11102-016-0754-x
2. 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.). https://doi.org/10.14341/probl1033
3. Colao A, Grasso LFS, Giustina A, et al. Acromegaly. Nat Rev Dis Prim. 2019;5(1):1-17. https://doi.org/10.1038/s41572-019-0071-6
4. Fleseriu M, Beverly Biller M, Freda PU, et al. A Pituitary Society update to acromegaly management guidelines. Pituitary. 2021;24:1-13. https://doi.org/10.1007/s11102-020-01091-7
5. Machado EO, Taboada GF, Neto LV, et al. Prevalence of discordant GH and IGF-I levels in acromegalics at diagnosis, after surgical treatment and during treatment with octreotide LAR. Growth Horm IGF Res. 2008;18(5):389-393. https://doi.org/10.1016/j.ghir.2008.02.001
6. Sherlock M, Toogood AA. Aging and the growth hormone/ insulin like growth factor-I axis. Pituitary. 2007;10(2):189-203. https://doi.org/10.1007/s11102-007-0039-5
7. Murray PG, Higham CE, Clayton PE. The hypothalamo-GH axis: The past 60 years. J Endocrinol. 2015;226(2):T123-T140. https://doi.org/10.1530/JOE-15-0120
8. Schilbach K, Bidlingmaier M. Laboratory investigations in the diagnosis and follow-up of GH-related disorders. Arch Endocrinol Metab. 2019;63(6):618-629. https://doi.org/10.20945/2359-3997000000192
9. Juul A. Serum levels of insulin-like growth factor I and its binding proteins in health and disease. Growth Horm IGF Res. 2003;13(4):113-170. https://doi.org/10.1016/S1096-6374(03)00038-8
10. Vestergaard PF, Hansen M, Frystyk J, et al. Serum levels of bioactive IGF1 and physiological markers of ageing in healthy adults. Eur J Endocrinol. 2014;170(2):229-236. https://doi.org/10.1530/EJE-13-0661
11. Rotwein P. Large-scale analysis of variation in the insulin-like growth factor family in humans reveals rare disease links and common polymorphisms. J Biol Chem. 2017;292(22):9252-9261. https://doi.org/10.1074/jbc.M117.783639
12. Dedov II, Molitvoslovova NN, Rozhinskaia LYa, et al. Russian association of endocrinologists national practice guidelines (clinical signs, diagnosis, differential diagnosis, treatment). Acromegaly. Problems of Endocrinology. 2013;59(6):4-18 (In Russ.). https://doi.org/10.14341/probl20135964-18
13. Penalva A, Burguera B, Cusahie X, et al. Activation of cholinergic neurotransmission by pyridostigmine reverses the inhibitory effect of hyperglycemia on growth hormone (GH) releasing hormoneinduced GH secretion in man: Does acute hyperglycemia act through hypothalamic release of somatostatin? Neuroendocrinology. 1989;49(5):551-554. https://doi.org/10.1159/000125166
14. [Molitvoslovova NN. Acromegaly: recent progress in diagnostics and treatment. Problems of Endocrinology. 2011;57(1):46-59 (In Russ.). https://doi.org/10.14341/probl201157146-59
15. Occhi G, Losa M, Albiger N, et al. The glucose-dependent insulinotropic polypeptide receptor is overexpressed amongst GNAS1 mutation-negative somatotropinomas and drives growth hormone (GH)-promoter activity in GH3 cells. J Neuroendocrinol. 2011;23(7):641-649. https://doi.org/10.1111/j.1365-2826.2011.02155.x
16. Giustina A, Barkhoudarian G, Beckers A, et al. Multidisciplinary management of acromegaly: A consensus. Rev Endocr Metab Disord. 2020;21(4):667-678. https://doi.org/10.1007/s11154-020-09588-z
17. Melmed S, Bronstein MD, Chanson P, et al. A Consensus Statement on acromegaly therapeutic outcomes. Nat Rev Endocrinol. 2018;14(9):552-561. https://doi.org/10.1038/s41574-018-0058-5
18. Paisley AN, Hayden K, Ellis A, et al. Pegvisomant interference in GH assays results in underestimation og GH levels. Eur J Endocrinol. 2007;156(3):315-319. https://doi.org/10.1530/eje.1.02341
19. Przhiyalkovskaya EG, Osmanova PO, Mamedova EO, et al. Predictive Biomarkers in the Treatment of Acromegaly: A Review of the Literature. Annals of the Russian Academy of Medical Sciences. 2019;74(6):430-440 (In Russ.). https://doi.org/10.15690/vramn1181
20. Capatina C, Wass JAH. Acromegaly. J Endocrinol. 2015;226(2):T141-T160. https://doi.org/10.1530/JOE-15-0109
21. Brzana JA, Yedinak CG, Delashaw JB, et al. Discordant growth hormone and IGF-1 levels post pituitary surgery in patients with acromegaly naïve to medical therapy and radiation: What to follow, GH or IGF-1 values? Pituitary. 2012;15(4):562-570. https://doi.org/10.1007/s11102-011-0369-1
22. Alexopoulou O, Bex M, Abs R, et al. Divergence between growth hormone and insulin-like growth factor-I concentrations in the follow-up of acromegaly. J Clin Endocrinol Metab. 2008;93(4):1324-1330. https://doi.org/10.1210/jc.2007-2104
23. Freda PU. Monitoring of acromegaly: what should be performed when GH and IGF-1 levels are discrepant? Clin Endocrinol (Oxf). 2009;71(2):166. https://doi.org/10.1111/J.1365-2265.2009.03556.X
24. Kanakis GA, Chrisoulidou A, Bargiota A, et al. The ongoing challenge of discrepant growth hormone and insulin-like growth factor I results in the evaluation of treated acromegalic patients: a systematic review and meta-analysis. Clin Endocrinol (Oxf). 2016;85(5):681-688. https://doi.org/10.1111/cen.13129
25. Butz LB, Sullivan SE, Chandler WF, et al. “Micromegaly”: an update on the prevalence of acromegaly with apparently normal GH secretion in the modern era. Pituitary. 2016;19(6):547-551. https://doi.org/10.1007/s11102-016-0735-0
26. Rosario PW, Calsolari MR. Elevated IGF-1 with GH suppression after an oral glucose overload: Incipient acromegaly or falsepositive IGF-1? Arch Endocrinol Metab. 2016;60(6):510-514. https://doi.org/10.1590/2359-3997000000193
27. Oldfield EH, Jane JA, Thorner MO, et al. Correlation between GH and IGF-1 during treatment for Acromegaly. J Neurosurg. 2017;126(6):1959-1966. https://doi.org/10.3171/2016.8.JNS161123
28. Ribeiro de Oliveira Longo Schweizer J, Ribeiro-Oliveira Jr A, Bidlingmaier M. Growth hormone: isoforms, clinical aspects and assays interference. Clin Diabetes Endocrinol. 2018;4(1):18. https://doi.org/10.1186/s40842-018-0068-1
29. Lindholm J, Giwercman B, Giwercman A, et al. Investigation of the criteria for assessing the outcome of treatment in acromegaly. Clin Endocrinol (Oxf). 1987;27(5):553-562. https://doi.org/10.1111/j.1365-2265.1987.tb01185.x
30. Melmed S, Ho K, Klibanski A, et al. Clinical review 75: Recent advances in pathogenesis, diagnosis, and management of acromegaly. J Clin Endocrinol Metab. 1995;80(12):3395-3402. https://doi.org/ 10.1210/jcem.80.12.8530571
31. Giustina A, Barkan A, Casanueva FF, et al. Criteria for Cure of Acromegaly: A Consensus Statement. J Clin Endocrinol Metab. 2000;85(2):526-529. https://doi.org/10.1210/jcem.85.2.6363
32. Pokrajac A, Wark G, Ellis AR, et al. Variation in GH and IGF-I assays limits the applicability of international consensus criteria to local practice. Clin Endocrinol (Oxf). 2007;67(1):65-70. https://doi.org/10.1111/j.1365-2265.2007.02836.x
33. Chanson P, Arnoux A, Mavromati M, et al. Reference Values for IGF-I Serum Concentrations: Comparison of Six Immunoassays. J Clin Endocrinol Metab. 2016;101(9):3450-3458. https://doi.org/10.1210/jc.2016-1257
34. Bonert V, Carmichael J, Wu Z, et al. Discordance between mass spectrometry and immunometric IGF-1 assay in pituitary disease: a prospective study. Pituitary. 2018;21(1):65-75. https://doi.org/10.1007/s11102-017-0849-z
35. Akirov A, Masri-Iraqi H, Dotan I, et al. The Biochemical Diagnosis of Acromegaly. J Clin Med. 2021;10(5):1-8. https://doi.org/10.3390/JCM10051147
36. Hage M, Kamenický P, Chanson P. Growth Hormone Response to Oral Glucose Load: From Normal to Pathological Conditions. Neuroendocrinology. 2019;108(3):244-255. https://doi.org/10.1159/000497214
37. Miell JP, Taylor AM, Zini M, et al. Effects of hypothyroidism and hyperthyroidism on insulin-like growth factors (IGFs) and growth hormoneand IGF-binding proteins. J Clin Endocrinol Metab. 1993;76(4):950-955. https://doi.org/10.1210/jcem.76.4.7682563
38. Iranmanesh A, Lizarralde G, Gohnson M, et al. Nature of altered growth hormone secretion in hyperthyroidism. J Clin Endocrinol Metab. 1991;72(1):108-115. https://doi.org/10.1210/jcem-72-1-108
39. Leung KC, Doyle N, Ballesteros M, et al. Insulin Regulation of Human Hepatic Growth Hormone Receptors: Divergent Effects on Biosynthesis and Surface Translocation1. J Clin Endocrinol Metab. 2000;85(12):4712-4720. https://doi.org/10.1210/jcem.85.12.7017
40. Giustina A, Bresciani E, Tassi C, et al. Effect of pyridostigmine on the growth hormone response to growth hormone-releasing hormone in lean and obese type II diabetic patients. Metabolism. 1994;43(7):893-898. https://doi.org/10.1016/0026-0495(94)90273-9
41. Kamenický P, Mazziotti G, Lombès M, et al. Growth hormone, insulin-like growth factor-1, and the kidney: Pathophysiological and clinical implications. Endocr Rev. 2014;35(2):234-281. https://doi.org/10.1210/er.2013-1071
42. Adamek A, Kasprzak A. Insulin-Like Growth Factor (IGF) System in Liver Diseases. Int J Mol Sci. 2018;19(5):1308. https://doi.org/10.3390/ijms19051308
43. Buttan A, Mamelak AN. Endocrine Outcomes After Pituitary Surgery. Neurosurg Clin N Am. 2019;30(4):491-498. https://doi.org/10.1016/j.nec.2019.05.009
44. Carmichael JD, Bonert VS, Mirocha JM, et al. The Utility of Oral Glucose Tolerance Testing for Diagnosis and Assessment of Treatment Outcomes in 166 Patients with Acromegaly. J Clin Endocrinol Metab. 2009;94(2):523-527. https://doi.org/10.1210/jc.2008-1371
45. Bianchi A, Giustina A, Cimino V, et al. Influence of growth hormone receptor d3 and full-length isoforms on biochemical treatment outcomes in acromegaly. J Clin Endocrinol Metab. 2009;94(6):2015-2022. https://doi.org/10.1210/jc.2008-1337
46. Freda PU, Nuruzzaman AT, Reyes CM, et al. Significance of “Abnormal” Nadir Growth Hormone Levels after Oral Glucose in Postoperative Patients with Acromegaly in Remission with Normal Insulin-Like Growth Factor-I Levels. J Clin Endocrinol Metab. 2004;89(2):495-500. https://doi.org/10.1210/jc.2003-031316
47. Graillon T, Castinetti F, Boucekine M, et al. Fluctuation analysis of postoperative secretory status in patients operated for acromegaly. Ann Endocrinol (Paris). 2020;81(1):11-17. https://doi.org/10.1016/j.ando.2019.11.002
48. Dal J, Klose M, Heck A, et al. Targeting either GH or IGF-I during somatostatin analogue treatment in patients with acromegaly: A randomized multicentre study. Eur J Endocrinol. 2018;178(1):65-74. https://doi.org/10.1530/eje-17-0546
49. Kuker AP, Shen W, Jin Z, et al. Body Composition Changes with Long-term Pegvisomant Therapy of Acromegaly. J Endocr Soc. 2021;5(3):1-12. https://doi.org/10.1210/jendso/bvab004
50. Giustina A, Arnaldi G, Bogazzi F, et al. Pegvisomant in acromegaly: an update. J Endocrinol Invest. 2017;40(6):577-589. https://doi.org/10.1007/s40618-017-0614-1
Supplementary files
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1. Рисунок. Схема физиологической регуляции синтеза и секреции соматотропного гормона и инсулиноподобного фактора роста 1. СТГ — соматотропный гормон, ИФР-1 — инсулиноподобный фактор роста 1, СТГ-РГ — соматолиберин. Стрелки указывают на стимулирующий (+) или угнетающий эффект (-) различных регуляторов. Адаптировано из: Wilkinson M., Imran S. Regulation of Growth Hormone Secretion. In Clinical Neuroendocrinology: An Introduction (pp. 134-153). Cambridge: Cambridge University Press; 2019. doi: 10.1017/9781108149938.009 | |
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For citations:
Sakhnova E.E., Przhiyalkovskaya E.G., Belaya Zh.E., Melnichenko G.A. Discordant parameters of insulin-like growth factor 1 and growth hormone in the diagnosis and monitoring of acromegaly. Problems of Endocrinology. 2022;68(1):40-48. (In Russ.) https://doi.org/10.14341/probl12791

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