Current aspects of diagnosis and treatment of adult GH-deficiency

Cover Page
Open Access Open Access
Restricted Access Access granted
Restricted Access Subscription Access


Adult growth hormone (GH) deficiency (AGHD) is a condition characterized by alterations in body composition, lipid and carbohydrate metabolism, bone mineral density and poor quality of life; however, clinical presentations of AGHD are mostly non-specific. Untreated AGHD is associated with increased cardiovascular morbidity and mortality. Stimulation tests are used for the diagnosis: insulin tolerance test, glucagon stimulation test, growth-hormone releasing hormone and arginine stimulation test. Moreover, in 2017 FDA approved the use of macimorelin (oral GH secretagogue) for the diagnosis of AGHD. In childhood GH-deficiency, apolipoprotein A-IV, CFHR4 (complement factor H-related protein 4) and PBP (platelet basic protein) were identified as potential biomarkers of the disease, however, this was not investigated in AGHD. GH treatment starts from the minimal dose, which allows minimizing the adverse effects. According to published meta-analyses, AGHD treatment generally does not lead to increased risk of malignancy and recurrence of sellar neoplasms in adult patients. Published data on GH receptor polymorphism associations with treatment efficacy remains controversial. Development of long-acting GH formulations is a currect perspective for the increase of treatment compliance.

Full Text

Restricted Access

About the authors

Alexander S. Lutsenko

Endocrinology Research Centre

Author for correspondence.
ORCID iD: 0000-0002-9314-7831
SPIN-code: 4037-1030

Russian Federation, 11, Dm. Ulyanova street, Moscow, 117036

research scientist of neuroendocrinology and bone diseases department

Elena V. Nagaeva

Endocrinology Research Centre

ORCID iD: 0000-0001-6429-7198
SPIN-code: 4878-7810

Russian Federation, 11 Dm.Ulyanova street, Moscow, 117036


Zhanna E. Belaya

Endocrinology Research Centre

ORCID iD: 0000-0002-6674-6441
SPIN-code: 4746-7173

Russian Federation, 11 Dm. Ulyanova street, 117036 Moscow

MD, PhD, Professor

Olga S. Chukhacheva

Endocrinology Research Centre

ORCID iD: 0000-0001-5675-5419
SPIN-code: 3484-6222

Russian Federation, 11, Dm. Ulyanova street, Moscow, 117036


Tatiana S. Zenkova

Endocrinology Research Centre

ORCID iD: 0000-0002-7724-1617
SPIN-code: 2154-5837

Russian Federation, 11, Dm. Ulyanova street, Moscow, 117036

PhD, MD in neuroendocrinology and bone diseases department

Galina A. Melnichenko

Endocrinology Research Centre

ORCID iD: 0000-0002-5634-7877
SPIN-code: 8615-0038

Russian Federation, 11 Dm. Ulyanova street, 117036 Moscow

MD, PhD, Professor


  1. Vorontsova MV. Incidence and prevalence of growth hormone deficiency in the russian federation according to the official medical statistics data and the growth hormone deficiency patients registry. Problemy endokrinologii. 2016;62(4):18-26. doi: 10.14341/probl201662418-26
  2. Vorontsova MV, Nagaeva EV, Naygovzina NB. Economic and social aspects of pituitary dwarfism treatment with recombinant growth hormone. Problemy endokrinologii. 2017;63(2):82−91. doi: 10.14341/probl201763282-91
  3. Jørgensen JO, Thuesen L, Ingemann-Hansen T, et al. Beneficial effects of growth hormone treatment in GH-deficient adults. Lancet. 1989;333(8649):1221-1225. doi:
  4. Salomon F, Cuneo RC, Hesp R, Sönksen PH. The effects of treatment with recombinant human growth hormone on body composition and metabolism in adults with growth hormone deficiency. N Engl J Med. 1989;321(26):1797-1803. doi:
  5. Dedov II, Bezlepkina OB, Koledova EB, et al. The first domestic experience with the use of human growth hormone in adult patients with growth hormone deficiency. Problemy endokrinologii. 2004;50(1):30-33.
  6. Bezlepkina OB. Sindrom gipofizarnoy karlikovosti u vzroslykh: diagnostika, klinika, mediko-sotsial’naya reabilitatsiya. [dissertation abstract] Moscow; 2004. 40 р.
  7. Bezlepkina OB, Nagaeva EV, Tsybina LV, et al. Densitometricheskaya otsenka vliyaniya chelovecheskogo gormona rosta na zhirovuyu i toshchuyu massu tela u vzroslykh patsientov s somatotropnoy nedostatochnost’yu. Osteoporosis and bone diseases. 2003;2:2-4.
  8. Mersebach H, Feldt-Rasmussen U. Growth hormone and body composition. In: Jørgensen JO, Christiansen JS (eds). Growth hormone deficiency in adults. Vol. 33. Basel: Karger; 2005. Рр. 185-195. doi:
  9. Vaks VV, Gerasimenko OA, Dzeranova LK. Priobretennaya nedostatochnost’ gormona rosta u vzroslykh: etiologiya, klinicheskie proyavleniya, diagnostika i vozmozhnosti lecheniya. Obesity and metabolism. 2011;8(2):11-17. doi: 10.14341/2071-8713-4947
  10. Mоller J, Frandsen E, Fisker S, et al. Decreased plasma and extracellular volume in growth hormone deficient adults and the acute and prolonged effects of GH administration: a controlled experimental study. Clin Endocrinol (Oxf). 1996;44(5):533-539. doi:
  11. Widdowson WM, Gibney J. The effect of growth hormone replacement on exercise capacity in patients with GH deficiency: a metaanalysis. J Clin Endocrinol Metab. 2008;93(11):4413-4417. doi:
  12. Juul A, Behrenscheer A, Tims T, et al. Impaired thermoregulation in adults with growth hormone deficiency during heat exposure and exercise. Clin Endocrinol (Oxf). 1993;38(3):237-244. doi:
  13. Dedov II, Bondarenko IZ, Bezlepkina OB. Endokrinnye mekhanizmy modulyatsii serdechnoydeyatel’nosti u patsientov s khronicheskoy serdechnoy nedostatochnost’yu: rol’ gormona rosta. Obesity and metabolism. 2010;7(4):4-7. doi: 10.14341/2071-8713-5080
  14. Gazzaruso C, Gola M, Karamouzis I, et al. Cardiovascular risk in adult patients with growth hormone (GH) deficiency and following substitution with gh – an update. J Clin Endocrinol Metab. 2014;99(1):18-29. doi:
  15. Johansson JO, Landin K, Tengborn L, et al. High fibrinogen and plasminogen activator inhibitor activity in growth hormone-deficient adults. Arterioscler Thromb A J Vasc Biol. 1994;14(3):434-437. doi:
  16. Giovannini L, Tirabassi G, Muscogiuri G, et al. Impact of adult growth hormone deficiency on metabolic profile and cardiovascular risk [Review]. Endocr J. 2015;62(12):1037-1048. doi:
  17. Bouillon R, Koledova E, Bezlepkina O, et al. Bone status and fracture prevalence in Russian adults with childhood-onset growth hormone deficiency. J Clin Endocrinol Metab. 2004;89(10):4993-4998. doi:
  18. Dedov II, Bezlepkina OB, Nagaeva EV, et al. Rasprostranennost’ perelomov pri gipopituitarizme. Osteoporosis and bone diseases. 2004;3:6-8.
  19. Mazziotti G, Doga M, Frara S, et al. Incidence of morphometric vertebral fractures in adult patients with growth hormone deficiency. Endocrine. 2016;52(1):103-110. doi:
  20. Rosilio M, Blum WF, Edwards DJ, et al. Long-term improvement of quality of life during growth hormone (GH) replacement therapy in adults with GH deficiency, as measured by questions on life satisfaction-hypopituitarism (QLS-H). J Clin Endocrinol Metab. 2004;89(4):1684-1693. doi:
  21. Boguszewski CL. Update on GH therapy in adults. F1000 Research. 2017;6:2017. doi:
  22. Yuen KC, Tritos NA, Samson SL, et al. American Association of Clinical Endocrinologists and American College of Endocrinology Disease State Clinical Review: update on growth hormone stimulation testing and proposed revised cut-point for the glucagon stimulation test in the diagnosis of adult. Endocr Pract. 2016;22(10):1235-1244. doi:
  23. Mukherjee A, Shalet SM. The value of IGF1 estimation in adults with GH deficiency. Eur J Endocrinol. 2009;161(suppl_1):S33−S39. doi:
  24. Molitch ME, Clemmons DR, Malozowski S, et al. Evaluation and treatment of adult growth hormone deficiency: an endocrine society clinical practice guideline. J Clin Endocrinol Metab. 2011; 96(6):1587−1609. doi:
  25. Nagaeva EV, Shiryaeva TY, Peterkova VA, et al. Russian national consensus. Diagnostics and treatment of hypopituitarism in children and adolescences. Problemy endokrinologii. 2018;64(6):402-411. doi: 10.14341/probl10091.
  26. Roth J, Glick SM, Yalow RS, Berson SA. Hypoglycemia: a potent stimulus to secretion of growth hormone. Science. 1963;140(3570): 987-988. doi:
  27. Lee P, Greenfield JR, Ho KK. Factors determining inadequate hypoglycaemia during insulin tolerance testing (ITT) after pituitary surgery. Clin Endocrinol (Oxf). 2009;71(1):82-85. doi:
  28. Aimaretti G, Corneli G, Razzore P, et al. Comparison between insulin-induced hypoglycemia and growth hormone (GH)-releasing hormone + arginine as provocative tests for the diagnosis of GH deficiency in adults 1. J Clin Endocrinol Metab. 1998;83(5):1615-1618. doi:
  29. Ghigo E, Aimaretti G, Arvat E. Growth hormone-releasing hormone combined with arginine or growth hormone secretagogues for the diagnosis of growth hormone deficiency in adults. Endocrine. 2001;15(1):029−038. doi:
  30. Barinaga M, Bilezikjian LM, Vale WW, et al. Independent effects of growth hormone releasing factor on growth hormone release and gene transcription. Nature. 1985;314(6008):279-281. doi:
  31. Alba-Roth J, Müller OA, Schopohl J, von Werder K. Arginine stimulates growth hormone secretion by suppressing endogenous somatostatin secretion. J Clin Endocrinol Metab. 1988;67(6):1186-1189. doi: 10.1210/jcem-67-6-1186.
  32. Darzy KH, Thorner MO, Shalet SM. Cranially irradiated adult cancer survivors may have normal spontaneous GH secretion in the presence of discordant peak GH responses to stimulation tests (compensated GH deficiency). Clin Endocrinol (Oxf). 2009; 70(2):287-293. doi:
  33. Ghigo E, Bartolotta E, Imperiale E, et al. Glucagon stimulates GH secretion after intramuscular but not intravenous administration. Evidence against the assumption that glucagon per se has a GH-releasing activity. J Endocrinol Invest. 1994;17(11):849-854. doi:
  34. Tavares AB, Seixas da Silva IA, Silvestre DH, et al. Potential risks of glucagon stimulation test in elderly people. Growth Horm IGF Res. 2015;25(1):53-56. doi:
  35. Gómez JM, Espadero RM, Escobar-Jiménez F, et al. Growth hormone release after glucagon as a reliable test of growth hormone assessment in adults. Clin Endocrinol (Oxf). 2002;56(3):329-334. doi:
  36. Conceição FL, da Costa e Silva A, Leal Costa AJ, Vaisman M. Glucagon stimulation test for the diagnosis of GH deficiency in adults. J Endocrinol Invest. 2003;26(11):1065-1070. doi:
  37. Boguszewski CL. Glucagon stimulation test: has its time come? Endocrine. 2017;57(3):361-363. doi:
  38. Bowers CY. GH releasing peptides ― structure and kinetics. J Pediatr Endocrinol. 1993;6(1):21-31. doi:
  39. Wang G, Lee HM, Englander E, Greeley GH. Ghrelin – not just another stomach hormone. Regul Pept. 2002;105(2):75-81. doi:
  40. Smith RG. Development of growth hormone secretagogues. Endocr Rev. 2005;26(3):346-360. doi:
  41. Yuen KC. Growth hormone stimulation tests in assessing adult growth hormone deficiency. In: Feingold KR, Anawalt B, Boyce A, et al., ed. Source Endotext [Internet]. South Dartmouth (MA): MD, Inc.; 2000-2019.
  42. Popovic V, Pekic S, Golubicic I, et al. The impact of cranial irradiation on GH responsiveness to GHRH plus GH-releasing peptide-6. J Clin Endocrinol Metab. 2002;87(5):2095-2099. doi:
  43. Procopio M, Maccario M, Savio P, et al. GH response to GHRH combined with pyridostigmine or arginine in different conditions of low somatotrope secretion in adulthood: obesity and Cushing’s syndrome in comparison with hypopituitarism. Panminerva Med. 1998;40(1):13-17.
  44. Gasperi M, Aimaretti G, Scarcello G, et al. Low dose hexarelin and growth hormone (GH)-releasing hormone as a diagnostic tool for the diagnosis of GH deficiency in adults: comparison with insulin-induced hypoglycemia test 1. J Clin Endocrinol Metab. 1999;84(8):2633-2637. doi:
  45. Petersenn S, Jung R, Beil FU. Diagnosis of growth hormone deficiency in adults by testing with GHRP-6 alone or in combination with GHRH: comparison with the insulin tolerance test. Eur J Endocrinol. 2002;146(5):667-672. doi:
  46. Cordido F, Alvarez-Castro P, Isidro ML, et al. Comparison between insulin tolerance test, growth hormone (GH)-releasing hormone (GHRH), GHRH plus acipimox and GHRH plus GH-releasing peptide-6 for the diagnosis of adult GH deficiency in normal subjects, obese and hypopituitary patients. Eur J Endocrinol. 2003;149(2):117-122. doi:
  47. Chihara K, Shimatsu A, Hizuka N, et al. A simple diagnostic test using GH-releasing peptide-2 in adult GH deficiency. Eur J Endocrinol. 2007;157(1):19-27. doi:
  48. Alaioubi B, Mann K, Petersenn S. Diagnosis of adrenal insufficiency using the GHRP-6 test: comparison with the insulin tolerance test in patients with hypothalamic-pituitary-adrenal disease. Horm Metab Res. 2010;42(3):198-203. doi:
  49. Popovic V, Leal A, Micic D, et al. GH-releasing hormone and GH-releasing peptide-6 for diagnostic testing in GH-deficient adults. Lancet. 2000;356(9236):1137-142. doi:
  50. Popovic V, Pekic S, Micic D, et al. Evaluation of the reproducibility of the GHRH plus GHRP-6 test of growth hormone reserve in adults. Clin Endocrinol (Oxf). 2004;60(2):185-191. doi:
  51. Kelestimur F, Popovic V, Leal A, et al. Effect of obesity and morbid obesity on the growth hormone (GH) secretion elicited by the combined GHRH + GHRP-6 test. Clin Endocrinol (Oxf). 2006;64(6):667-671. doi:
  52. Fukuda I, Hizuka N, Muraoka T, Ichihara A. Adult growth hormone deficiency: current concepts. Neurol Med Chir (Tokyo). 2014;54(8):599-605. doi:
  53. Gasco V, Beccuti G, Baldini C, et al. Acylated ghrelin as a provocative test for the diagnosis of GH deficiency in adults. Eur J Endocrinol. 2013;168(1):23-30. doi:
  54. Center for drug evaluation and research. Macrilen for oral solution: application number 205598Orig1s000 [Internet]. Available from:
  55. Piccoli F, Degen L, MacLean C, et al. Pharmacokinetics and pharmacodynamic effects of an oral ghrelin agonist in healthy subjects. J Clin Endocrinol Metab. 2007;92(5):1814-1820. doi:
  56. Garcia JM, Swerdloff R, Wang C, et al. Macimorelin (AEZS-130)-stimulated growth hormone (GH) test: validation of a novel oral stimulation test for the diagnosis of adult GH deficiency. J Clin Endocrinol Metab. 2013;98(6):2422-2429. doi:
  57. Garcia JM, Biller BM, Korbonits M, et al. Macimorelin as a diagnostic test for adult GH deficiency. J Clin Endocrinol Metab. 2018;103(8):3083-3093. doi:
  58. Junnila RK, Strasburger CJ, Bidlingmaier M. Pitfalls of insulin-like growth factor-I and growth hormone assays. Endocrinol Metab Clin North Am. 2015;44(1):27-34. doi:
  59. Clemmons DR. Consensus statement on the standardization and evaluation of growth hormone and insulin-like growth factor assays. Clin Chem. 2011;57(4):555-559. doi:
  60. Ortea I, Ruiz-Sánchez I, Cañete R, et al. Identification of candidate serum biomarkers of childhood-onset growth hormone deficiency using SWATH-MS and feature selection. J Proteomics. 2018;175:105-113. doi:
  61. Godowski PJ, Leung DW, Meacham LR, et al. Characterization of the human growth hormone receptor gene and demonstration of a partial gene deletion in two patients with laron-type dwarfism. Proc Natl Acad Sci. 1989;86(20):8083-8087. doi:
  62. Dos Santos C, Essioux L, Teinturier C, et al. A common polymorphism of the growth hormone receptor is associated with increased responsiveness to growth hormone. Nat Genet. 2004;36(7):720-724. doi:
  63. Ben-Avraham D, Govindaraju DR, Budagov T, et al. The GH receptor exon 3 deletion is a marker of male-specific exceptional longevity associated with increased GH sensitivity and taller stature. Sci Adv. 2017;3(6):e1602025. doi:
  64. Glad CA, Barbosa EJ, Filipsson Nyström H, et al. SNPs within the GH-signaling pathway are associated with the early IGF1 response to GH replacement therapy in GHD adults. Eur J Endocrinol. 2014;170(1):101-107. doi:
  65. Moyes VJ, Walker DM, Owusu-Antwi S, et al. D3-GHR genotype does not explain heterogeneity in GH responsiveness in hypopituitary adults. Clin Endocrinol (Oxf). 2009;72(6):807-813. doi:
  66. Meyer S, Schaefer S, Stolk L, et al. Association of the exon 3 deleted/full-length GHR polymorphism with recombinant growth hormone dose in growth hormone-deficient adults. Pharmacogenomics. 2009;10(10):1599-1608. doi:
  67. Mormando M, Chiloiro S, Bianchi A, et al. Growth hormone receptor isoforms and fracture risk in adult-onset growth hormone-deficient patients. Clin Endocrinol (Oxf). 2016;85(5):717-724. doi:
  68. Barbosa EJ, Palming J, Glad CA, et al. Influence of the exon 3-deleted/full-length growth hormone (GH) receptor polymorphism on the response to GH replacement therapy in adults with severe GH deficiency. J Clin Endocrinol Metab. 2009;94(2):639-644. doi:
  69. Andujar-Plata P, Fernandez-Rodriguez E, Quinteiro C, et al. Influence of the exon 3 deletion of GH receptor and IGF-I level at diagnosis on the efficacy and safety of treatment with somatotropin in adults with GH deficiency. Pituitary. 2015;18(1):101-107. doi:
  70. Adetunji OR, Blair JC, Javadpour M, et al. Deletion of exon 3 in the growth hormone receptor gene in adults with growth hormone deficiency: comparison of symptomatic and asymptomatic patients. Clin Endocrinol (Oxf). 2010;72(3):422-423. doi:
  71. Adetunji OR, MacFarlane IA, Javadpour M, A et al. The d3/fl-GH receptor gene polymorphism does not influence quality of life and body composition in GH-deficient adults receiving GH replacement therapy. Eur J Endocrinol. 2009;161(4):541-546. doi:
  72. Van der Klaauw AA, van der Straaten T, Baak-Pablo R, et al. Influence of the d3-growth hormone (GH) receptor isoform on short-term and long-term treatment response to GH replacement in GH-deficient adults. J Clin Endocrinol Metab. 2008;93(7):2828-2834. doi:
  73. Giavoli C, Ferrante E, Profka E, et al. Influence of the d3GH receptor polymorphism on the metabolic and biochemical phenotype of GH-deficient adults at baseline and during short- and long-term recombinant human GH replacement therapy. Eur J Endocrinol. 2010;163(3):361-368. doi:
  74. Reed ML, Merriam GR, Kargi AY. Adult growth hormone deficiency ― benefits, side effects, and risks of growth hormone replacement. Front Endocrinol (Lausanne). 2013;4:64. doi:
  75. Bex M, Abs R, Maiter D, et al. The effects of growth hormone replacement therapy on bone metabolism in adult-onset growth hormone deficiency: a 2-year open randomized controlled multicenter trial. J Bone Miner Res. 2002;17(6):1081-1094. doi:
  76. Underwood LE, Attie KM, Baptista J. Growth hormone (GH) dose-response in young adults with childhood-onset GH deficiency: a two-year, multicenter, multiple-dose, placebo-controlled study. J Clin Endocrinol Metab. 2003;88(11):5273−5280. doi:
  77. Shalet SM, Shavrikova E, Cromer M, et al. Effect of growth hormone (GH) treatment on bone in postpubertal GH-deficient patients: a 2-year randomized, controlled, dose-ranging study. J Clin Endocrinol Metab. 2003;88(9):4124-4129. doi:
  78. Mauras N, Pescovitz OH, Allada V, et al. Limited efficacy of growth hormone (GH) during transition of GH-deficient patients from adolescence to adulthood: a phase III multicenter, double-blind, randomized two-year trial. J Clin Endocrinol Metab. 2005;90(7):3946−3955. doi:
  79. Yang H, Wang L, Qiu X, et al. Body composition and metabolic health of young male adults with childhood-onset multiple pituitary hormone deficiency after cessation of growth hormone treatment. J Pediatr Endocrinol Metab. 2018;31(5):533-537. doi:
  80. Kokshoorn NE, Biermasz NR, Roelfsema F, et al. GH replacement therapy in elderly GH-deficient patients: a systematic review. Eur J Endocrinol. 2011;164(5):657-665. doi:
  81. Toogood AA, O’Neill PA, Shalet SM. Beyond the somatopause: growth hormone deficiency in adults over the age of 60 years. J Clin Endocrinol Metab. 1996;81(2):460-465. doi:
  82. Nagaeva EV. Klinicheskie, gormonal’nye i metabolicheskie proyavleniya vrozhdennoy somatotropnoy nedostatochnosti u vzroslykh karlikov na fone zamestitel’noy terapii gormonom rosta. [dissertation] Moscow; 2002.
  83. Span JP, Pieters GF, Sweep CG, et al. Gender difference in insulin-like growth factor I response to growth hormone (GH) treatment in GH-deficient adults: role of sex hormone replacement. J Clin Endocrinol Metab. 2000;85(3):1121-1125. doi:
  84. Clayton PE, Cowell CT. Safety issues in children and adolescents during growth hormone therapy – a review. Growth Horm IGF Res. 2000;10(6):306-317. doi:
  85. Malozowski S, Tanner LA, Wysowski D, Fleming GA. Growth hormone, insulin-like growth factor I, and benign intracranial hypertension. N Engl J Med. 1993;329(9):665-666. doi:
  86. Koller EA, Green L, Gertner JM, et al. Retinal changes mimicking diabetic retinopathy in two nondiabetic, growth hormone-treated patients 1. J Clin Endocrinol Metab. 1998;83(7):2380-2383. doi:
  87. Filipsson H, Johannsson G. GH replacement in adults: interactions with other pituitary hormone deficiencies and replacement therapies. Eur J Endocrinol. 2009;161(suppl 1):S85-S95. doi:
  88. Feldt-Rasmussen U, Klose M. Central hypothyroidism and its role for cardiovascular risk factors in hypopituitary patients. Endocrine. 2016;54(1):15-23. doi:
  89. Glynn N, Kenny H, Quisenberry L, et al. The effect of growth hormone replacement on the thyroid axis in patients with hypopituitarism: in vivo and ex vivo studies. Clin Endocrinol (Oxf). 2017;86(5):747-754. doi:
  90. Weissberger AJ, Ho KK, Lazarus L.Contrasting effects of oral and transdermal routes of estrogen replacement therapy on 24-hour growth hormone (GH) secretion, insulin-like growth factor I, and GH-binding protein in postmenopausal women. J Clin Endocrinol Metab. 1991;72(2):374-381. doi:
  91. Wolthers T, Hoffman DM, Nugent AG, et al. Oral estrogen antagonizes the metabolic actions of growth hormone in growth hormone-deficient women. Am J Physiol Metab. 2001;281(6):E1191-E1196. doi:
  92. Brooke AM, Kalingag LA, Miraki-Moud F, et al. Dehydroepiandrosterone (DHEA) replacement reduces growth hormone (GH) dose requirement in female hypopituitary patients on GH replacement. Clin Endocrinol (Oxf). 2006;65(5):673-680. doi:
  93. Renehan AG, Zwahlen M, Minder C, et al. Insulin-like growth factor (IGF)-I, IGF binding protein-3, and cancer risk: systematic review and meta-regression analysis. Lancet. 2004;363(9418): 1346-1353. doi:
  94. Dal J, Leisner MZ, Hermansen K, et al. Cancer incidence in patients with acromegaly: a cohort study and meta-analysis of the literature. J Clin Endocrinol Metab. 2018;103(6):2182-2188. doi:
  95. Olsson DS, Trimpou P, Hallén T, et al. Life expectancy in patients with pituitary adenoma receiving growth hormone replacement. Eur J Endocrinol. 2017;176(1):67-75. doi:
  96. Li Z, Zhou Q, Li Y, et al. Growth hormone replacement therapy reduces risk of cancer in adult with growth hormone deficiency: a meta-analysis. Oncotarget. 2016;7(49):81862-81869. doi:
  97. Pekic S, Stojanovic M, Popovic V. Controversies in the risk of neoplasia in GH deficiency. Best Pract Res Clin Endocrinol Metab. 2017;31(1):35−47. doi:
  98. McKenna SP, Doward LC, Alonso J, et al. The QoL-AGHDA: an instrument for the assessment of quality of life in adults with growth hormone deficiency. Qual Life Res. 1999;8(4):373-383. doi:
  99. Revicki DA, Leidy NK, Howland L. Evaluating the psychometric characteristics of the psychological general well-being index with a new response scale. Qual Life Res. 1996;5(4):419-425. doi:
  100. Hazem A, Elamin MB, Bancos I, et al. Body composition and quality of life in adults treated with GH therapy: a systematic review and meta-analysis. Eur J Endocrinol. 2012;166(1):13-20. doi:
  101. Van Bunderen CC, van Nieuwpoort IC, Arwert LI, et al. Does growth hormone replacement therapy reduce mortality in adults with growth hormone deficiency? Data from the Dutch National Registry of growth hormone treatment in adults. J Clin Endocrinol Metab. 2011;96(10):3151-3159. doi:
  102. Gaillard RC, Mattsson AF, Аkerblad AC, et al. Overall and cause-specific mortality in GH-deficient adults on GH replacement. Eur J Endocrinol. 2012;166(6):1069−1077. doi:
  103. Pappachan JM, Raskauskiene D, Kutty VR, Clayton RN. Excess mortality associated with hypopituitarism in adults: a meta-analysis of observational studies. J Clin Endocrinol Metab. 2015;100(4):1405-1411. doi:
  104. Stochholm K, Johannsson G. Reviewing the safety of GH replacement therapy in adults. Growth Horm IGF Res. 2015;25(4):149-157. doi:
  105. Vorotnikova SYu, Pigarova EA, Dzeranova LK. Metabolicheskie effekty gormona rosta. Obesity and metabolism. 2011;8(4):55-59. doi: 10.14341/2071-8713-5308
  106. Newman CB, Carmichael JD, Kleinberg DL. Effects of low dose versus high dose human growth hormone on body composition and lipids in adults with GH deficiency: a meta-analysis of placebo-controlled randomized trials. Pituitary. 2015;18(3):297-305. doi:
  107. Maison P, Chanson P. Cardiac effects of growth hormone in adults with growth hormone deficiency. Circulation. 2003;108(21): 2648-2652. doi:
  108. Kablak-Ziembicka A. Association of increased carotid intima-media thickness with the extent of coronary artery disease. Heart. 2004;90(11):1286-1290. doi:
  109. Gibney J, Wallace JD, Spinks T, et al. The effects of 10 years of recombinant human growth hormone (GH) in adult GH-deficient patients. J Clin Endocrinol Metab. 1999;84(8):2596-2602. doi:
  110. Maison P, Griffin S, Nicoue-Beglah M, et al. Impact of growth hormone (GH) treatment on cardiovascular risk factors in GH-deficient adults: a metaanalysis of blinded, randomized, placebo-controlled trials. J Clin Endocrinol Metab. 2004;89(5):2192-2199. doi:
  111. Giagulli VA, Castellana M, Perrone R, et al. GH supplementation effects on cardiovascular risk in GH deficient adult patients: a systematic review and meta-analysis. Endocr Metab Immune Disord Drug Targets. 2017;17(4):285-296. doi:
  112. Wieringa G, Toogood AA, Ryder WD, et al. Changes in lipoprotein(a) levels measured by six kit methods during growth hormone treatment of growth hormone-deficient adults. Growth Horm IGF Res. 2000;10(1):14-19. doi:
  113. Tritos NA, Klibanski A. Effects of growth hormone on bone. Prog Mol Biol Transl Sci. 2016;138:193-211. doi:
  114. Biller BM, Sesmilo G, Baum HB, et al. Withdrawal of long-term physiological growth hormone (GH) administration: differential effects on bone density and body composition in men with adult-onset GH deficiency 1. J Clin Endocrinol Metab. 2000;85(3):970-976. doi:
  115. Allo Miguel G, Serraclara Plá A, Partida Muñoz ML, et al. Seven years of follow up of trabecular bone score, bone mineral density, body composition and quality of life in adults with growth hormone deficiency treated with rhGH replacement in a single center. Ther Adv Endocrinol Metab. 2016;7(3):93-100. doi:
  116. Appelman-Dijkstra NM, Claessen KM, Hamdy NA, et al. Effects of up to 15 years of recombinant human GH (rhGH) replacement on bone metabolism in adults with Growth Hormone Deficiency (GHD): The Leiden Cohort Study. Clin Endocrinol (Oxf). 2014;81(5):727-735. doi:
  117. Xue P, Wang Y, Yang J, Li Y. Effects of growth hormone replacement therapy on bone mineral density in growth hormone deficient adults: a meta-analysis. Int J Endocrinol. 2013;2013:216107. doi:
  118. Barake M, Klibanski A, Tritos NA. Effects of recombinant human growth hormone therapy on bone mineral density in adults with growth hormone deficiency: a meta-analysis. J Clin Endocrinol Metab. 2014;99(3):852-860. doi:
  119. Appelman-Dijkstra NM, Claessen KM, Roelfsema F, et al. Therapy of endocrine disease: long-term effects of recombinant human GH replacement in adults with GH deficiency: a systematic review. Eur J Endocrinol. 2013;169(1):R1-R14. doi:
  120. Díez JJ, Sangiao-Alvarellos S, Cordido F. Treatment with growth hormone for adults with growth hormone deficiency syndrome: benefits and risks. Int J Mol Sci. 2018;19(3):893. doi:
  121. Committee for Medicinal Products for Human Use (CHMP) Assessment report Somatropin Biopartners International non-proprietary name: somatropin. EMA/CHMP/229458/2013 [Internet]. Available from: report/somatropin-biopartners-epar-public-assessment-report_en.pdf.
  122. European Medicines Agency. Somatropin Biopartners [Internet]. Available from:
  123. Hоybye C, Cohen P, Hoffman AR, et al. Status of long-acting-growth hormone preparations − 2015. Growth Horm IGF Res. 2015; 25(5):201-206. doi:
  124. Christiansen JS, Backeljauw PF, Bidlingmaier M, et al. Growth hormone research society perspective on the development of long-acting growth hormone preparations. Eur J Endocrinol. 2016;174(6):C1-C8. doi:



Abstract - 772

PDF (Russian) - 6

Remote (Russian) - 383




Copyright (c) 2020 Lutsenko A.S., Nagaeva E.V., Belaya Z.E., Chukhacheva O.S., Zenkova T.S., Melnichenko G.A.

Creative Commons License
This work is licensed under a Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International License.

This website uses cookies

You consent to our cookies if you continue to use our website.

About Cookies