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Evaluation of Safety and Efficacy of Growth Hormone Therapy by IGF-1 Z Score in Children with Short Stature



This study aims to explore the safety and efficacy of growth hormone (GH) therapy by retrospectively analyzing the changes of insulin-like growth factor-1 (IGF-1) Z-scores in children with short stature after treatment with GH.


The etiology of 104 children with short stature was classified according to the GH stimulation test and IGF-1 levels: (1) growth hormone deficiency (GHD); (2) mild growth hormone deficiency (M-GHD); (3) idiopathic short stature (ISS); (4) GH insensitivity syndrome (GHIS). In addition, all patients were treated with recombinant human growth hormone (rhGH) for 12 months, and the growth rate (Gv), height, body mass, bone age, height standard deviation scores (HtSDS), IGF-1 and adverse reactions were compared among these three groups before and after treatment.


The height, body mass, Gv and HtSDS were significantly higher in each group compared with those before treatment. Furthermore, the Z-score of IGF-1 significantly increased after 1 month of GH treatment and was positively correlated with the dosage of GH. Moreover, the difference in standard deviation score was significantly positively correlated with the increase in standard deviation score of IGF-1.


The detection of the GH-IGF-1 axis function can be carried out for the etiologic diagnosis of short stature. IGF-1 increased after rhGH treatment, and IGF-1 level was correlated to the time of therapy and dosage of GH. IGF-1-based GH dosing targeted to age- and gender-adjusted means may save medical costs and offer a more dose-sparing and potentially safer mode of therapy compared with traditional weight-based dosing.

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  1. Zelazowska-Rutkowska B, Trusiak M, Bossowski A, Cylwik B. Diagnostic usefulness of insulin-like growth factor 1 and insulin-like growth factor binding protein 3 in children with suspected pituitary dwarfism. Clin Lab. 2018;64(5):759–65.

    CAS  PubMed  Google Scholar 

  2. Lee JJ, Mitchell PD, Hood HC, Grand RJ, Cohen LE. Potential role of IGF-1 Z score to predict permanent linear growth impairment in children with IBD. J Pediatr Gastroenterol Nutr. 2014;58(4):472–6.

    CAS  Article  PubMed  Google Scholar 

  3. Im M, Kim YD, Han HS. Effect of growth hormone treatment on children with idiopathic short stature and idiopathic growth hormone deficiency. Ann Pediatr Endocrinol Metab. 2017;22(2):119–24.

    Article  PubMed  PubMed Central  Google Scholar 

  4. Rosenfield RG. The molecular basis of idiopathic short stature. Growth Horm IGF Res. 2005;15(suppl A):S3–5.

    Article  CAS  Google Scholar 

  5. Şiklar Z, Berberoglu M. Syndromic disorders with short stature. J Clin Res Pediatr Endocrinol. 2014;6(1):1–8.

    Article  PubMed  PubMed Central  Google Scholar 

  6. Zong XN, Li H, Wu HH, Zhang YQ. Socioeconomic development and secular trend in height in China. Econ Hum Biol. 2015;19:258–64.

    Article  PubMed  Google Scholar 

  7. Li H, Ji CY, Zong XN, Zhang YQ. Height and weight standardized growth charts for Chinese children and adolescents aged 0 to 18 years. Zhonghua er ke za zhi. 2009;47(7):487–92 (Chinese Journal of Pediatrics).

    PubMed  Google Scholar 

  8. Goldstein H, Cameron N, Healy JM, Tanner M. Assessment of skeletal maturity and predication of adult height (TW3 method). Gov Oppos. 2001;36(1):27–47.

    Article  Google Scholar 

  9. Zhang SY, Liu LJ, Wu ZL, Liu G, Ma ZG, Shen XZ, et al. Standards of TW3 skeletal maturity for Chinese children. Ann Hum Biol. 2008;35(3):349–54.

    Article  PubMed  Google Scholar 

  10. Plotsky PM, Vale W. Patterns of growth hormone-releasing factor and somatostatin secretion into the hypophysial-portal circulation of the rat. Science. 1985;230(4724):461–3.

    CAS  Article  PubMed  Google Scholar 

  11. Bhat N, Dulmovits E, Lane A, Messina C, Wilson T. Combined simultaneous arginine clonidine stimulation test: timing of peak growth hormone (GH) concentration and correlation with clinical indices of GH status. Growth Horm IGF Res. 2018;40:28–31.

    CAS  Article  PubMed  Google Scholar 

  12. Kang MJ. Novel genetic cause of idiopathic short stature. Ann Pediatr Endocrinol Metab. 2017;22(3):153–7.

    Article  PubMed  PubMed Central  Google Scholar 

  13. Schwarz HP, Birkholz-Walerzak D, Szalecki M, Walczak M, Galesanu C, Metreveli D, Khan-Boluki J, Schuck E. One-year data from a long-term phase IV study of recombinant human growth hormone in short children born small for gestational age. Biol Ther. 2014;4(1–2):1–13. (Epub 2014 Jan 28).

    Article  PubMed  PubMed Central  Google Scholar 

  14. Granada M, Murillo J, Lucas A, Salinas I, Llopis MA, Castells I, Foz M, Sanmarti A. Diagnostic efficiency of serum IGF-1, IGFbinding protein-3(IGFBP3), IGF-1/IGFBP3 molar ratio and urinary GH measurements in the diagnosis of adult GH deficiency: importance of an appropriate reference population. Eur J Endocrinol. 2000;142(3):243–53.

    CAS  Article  PubMed  Google Scholar 

  15. Walker JL, Ginalska-Malinowska M, Romer TE, Pucilowska JB, Underwood LE. Effects of the infusion of insulin-like growth factor I in a child with growth hormone insensitivity syndrome (Laron dwarfism). N Engl J Med. 1991;324(21):1483–8.

    CAS  Article  PubMed  Google Scholar 

  16. Ren S, Nie Y, Wang A. Effects of recombinant human growth hormone in the treatment of dwarfism and relationship between IGF-1, IGFBP-3 and thyroid hormone. Exp Ther Med. 2016;12(6):3579–82.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  17. Zhang Y, Zhang M, Chu Y, Ji B, Shao Q, Ban B. Association between growth hormone-insulin-like growth factor-1 axis gene polymorphisms and short stature in chinese children. Biomed Res Int. 2018;2018:7431050.

    PubMed  PubMed Central  Google Scholar 

  18. Cohen P, Clemmons DR, Eosenfield RG. Does the GH-IGF axis play a role in cancer pathogenesis? Growth Horm IGF Res. 2000;10(6):297–305.

    CAS  Article  PubMed  Google Scholar 

  19. Reynolds CM, Perry JK, Vickers MH. Manipulation of the growth hormone-insulin-like growth factor (GH-IGF) axis: a treatment strategy to reverse the effects of early life developmental programming. Int J Mol Sci. 2017;18(8):1729.

    Article  CAS  PubMed Central  Google Scholar 

  20. Oberle M, Grimberg A, Bamba V. Treatment of pre-pubertal patients with growth hormone deficiency: patterns in growth hormone dosage and insulin-like growth factor-I Z-scores. J Clin Res Pediatr Endocrinol. 2017;9(3):208–15.

    Article  PubMed  PubMed Central  Google Scholar 

  21. Takeda A, Cooper K, Bird A, Baxter L, Frampton GK, Gospodarevskaya E, Welch K, Bryant J. Recombinant human growth hormone for the treatment of growth disorders in children: a systematic review and economic evaluation. Health Technol Assess. 2010;14(42):1–209.

    CAS  Article  PubMed  Google Scholar 

  22. Mavromati M, Kuhn E, Agostini H, Brailly-Tabard S, Massart C, Piketty ML, Arnoux A, Young J, Souberbielle JC, Chanson P. Classification of patients with gh disorders may vary according to the IGF-I assay. J Clin Endocrinol Metab. 2017;102(8):2844–52.

    Article  PubMed  Google Scholar 

  23. Blum WF, Alherbish A, Alsagheir A, El Awwa A, Kaplan W, Koledova E, Savage MO. The growth hormone-insulin-like growth factor-I axis in the diagnosis and treatment of growth disorders. Endocr Connect. 2018;7(6):R212–22.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

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We thank the participants of the study.


No funding or sponsorship was received for this study or publication of this article. The Rapid Service Fee was funded by the authors.


All named authors meet the International Committee of Medical Journal Editors (ICMJE) criteria for authorship for this article, take responsibility for the integrity of the work as a whole, and have given their approval for this version to be published.

Authorship Contributions

All authors have contributed significantly to the manuscript and declare that the work is original and has not been submitted or published elsewhere.


Hui-Juan Liu, Ling-Hong Wang and Lu Chen have nothing to disclose.

Compliance with Ethics Guidelines

This study was conducted in accordance with the Declaration of Helsinki. This study was conducted with approval from the Ethics Committee of Henan Provincial People’s Hospital. Written informed consent was obtained from all participants.

Data Availability

The datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request.

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Correspondence to Hui-Juan Liu.

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Liu, HJ., Wang, LH. & Chen, L. Evaluation of Safety and Efficacy of Growth Hormone Therapy by IGF-1 Z Score in Children with Short Stature. Adv Ther 36, 2374–2383 (2019).

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  • Endocrinology
  • Growth hormone
  • Short status
  • Z-score of insulin-like growth factor-1