Startseite Growth and metabolic effects of long-term recombinant human growth hormone (rhGH) treatment in short children born small for gestational age: GH-RAST study
Artikel
Lizenziert
Nicht lizenziert Erfordert eine Authentifizierung

Growth and metabolic effects of long-term recombinant human growth hormone (rhGH) treatment in short children born small for gestational age: GH-RAST study

  • José I. Labarta , Antonio de Arriba , Marta Ferrer , Marisa Loranca , José María Martos , Amparo Rodríguez , María Luz Samaniego und Laura Sánchez-Cenizo ORCID logo EMAIL logo
Veröffentlicht/Copyright: 5. Juli 2020
Journal of Pediatric Endocrinology and Metabolism
Aus der Zeitschrift Journal of Pediatric Endocrinology and Metabolism Band 33 Heft 7

Abstract

Objectives

To study the efficacy and influence on metabolism of recombinant human growth hormone (rhGH) treatment in short children born small for gestational age (SGA).

Methods

Retrospective, observational, multicenter study in 305 short children born SGA, treated with rhGH during a mean ± SD of 5.03 ± 1.73 years at a mean ± SD dose of 37 ± 8 μg/kg/day. Auxological and metabolic assessment including glucose and lipids profile were collected.

Results

Mean ± SD age at the start of treatment was 7.11 ± 2.78 years. Height and weight improved significantly until the end of treatment from mean −2.72 (CI95%: −2.81 to −2.63) standard deviation score (SDS) to −1.16 (CI95%: −1.44 to −0.88) SDS and from −1.62 (CI95%: −1.69 to −1.55) SDS to −0.94 (CI95%: −1.14 to −0.74) SDS respectively. Mean height gain was 1.27 (CI95%: 0.99–1.54) SDS. Prepubertal patients showed higher height gain than pubertal children (mean [CI95%] = 1.44 [CI95%: 1.14–1.74] vs. 0.73 [CI95%: 0.22–1.24], p=0.02). Height gain SDS during treatment negatively correlated with chronological age (CA) and bone age (BA) delay and positively correlated with duration of treatment, height gain during first year of treatment, years on prepubertal treatment and height SDS from target height (TH). Glucose, insulin, and triglycerides increased significantly but remained within the normal range. Total and LDL-cholesterol decreased significantly, and HDL-cholesterol remained unchanged.

Conclusions

rhGH treatment in short SGA children effectively normalized height in most of the patients and showed a safe metabolic profile. Children who benefit the most are those with greater height SDS distance from TH, BA delay, longer duration of treatment and prepubertal treatment initiation.

Keywords: growth hormone; height; small for gestational age; somatropin metabolism
Corresponding author: Laura Sánchez-Cenizo, PhD, Pfizer S.L.U., Avda. Europa, 20B, Parque Empresarial La Moraleja, 28108, Alcobendas, Madrid, Spain. Phone: +34 914909900, E-mail:

Funding source: Pfizer Spain

Acknowledgements

The authors thank all the investigators of GH-RAST study and participant patients at Hospital Miguel Servet, Zaragoza (Dr. E. Mayayo and Dr. JI Labarta), Hospital Vall d’Hebron, Barcelona (Dr. A. Carrascosa), Hospital Marqués de Valdecilla, Santander (Dr. C. Luzuriaga), Hospital Sant Juan de Deu, Barcelona (Dr. L. Ibañez), Hospital Universitario Sagrat Cor, Barcelona (Dr. N. Cabrinety), Hospital Germans Trias i Pujol, Barcelona (Dr. J. Bel), Hospital Clínico Universitario, Valladolid (Dr. F. Hermoso), Hospital Carlos Haya, Málaga (Dr. JP López-Siguero and Dr. MJ Martínez-Aedo), Hospital Universitario La Paz, Madrid (Dra. I. González-Casado), Hospital Virgen de la Arrixaca, Murcia (Dr. A. Macías and JM Marcos), Hospital Gregorio Marañón, Madrid (Dr. MD. Rodriguez Arnao and A. Rodriguez), Hospital Virgen del Camino, Pamplona (Dr. M. Oyartzabal) and Centro Médico1, Madrid (Dr. M. Loranca).

  1. Research funding: This research was sponsored and funded by Pfizer (Spain).

  2. Author contributions: All the authors have accepted responsibility for the entire content of this submitted manuscript and approved submission. NM, LS-C and JIL participated in the conceptualization and design of the study. JIL, ML, JMM and AA participated in the data collection. JIL, MLS, NM and LS-C, participated in the analysis and interpretation of results, and actively reviewed the manuscript. JIL, MF, AA and LS-C wrote the first draft of the manuscript. All authors contributed to draft the manuscript, and they read, modified and approved the final version. LS-C and MLS had full access to all the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis.

  3. Competing interests: The funding organization, Pfizer (Spain), together with two Coordinating Investigators, played a role in the study design; in the analysis and interpretation of data; in the writing of the report; and in the decision to submit the report for publication.

  4. Informed consent: Informed consent was obtained from all individuals included in this study.

  5. Ethical approval: The research related to human use has been complied with all the relevant national regulations, institutional policies and in accordance the tenets of the Helsinki Declaration, and has been approved by the Ethics Committee of each participant center.

References

1. Albertsson-Wikland, K, Boguszewski, M, Karlberg, J. Children born small-for-gestational age: postnatal growth and hormonal status. Horm Res 1998;49:7–13. https://doi.org/10.1159/000053080.Suche in Google Scholar

2. Clayton, P, Cianfarani, S, Czernichow, P, Johannsson, G, Rapaport, R, Rogol, A. Management of the child born small for gestational age through to adulthood: a consensus statement of the International Societies of Pediatric Endocrinology and the Growth Hormone Research Society. J Clin Endocrinol Metab 2007;92:804–10. https://doi.org/10.1210/jc.2006-2017.Suche in Google Scholar

3. Saenger, P, Czernichow, P, Hughes, I, Reiter, E. Small for gestational age: short stature and beyond. Endocr Rev 2007;28:219–51. https://doi.org/10.1210/er.2006-0039.Suche in Google Scholar

4. Ranke, M, Lindberg, A, Board, KI. Prediction models for short children born small for gestational age (SGA) covering the total growth phase. Analyses based on data from KIGS (Pfizer International Growth Database). BMC Med Inf Decis Making 2011;11. https://doi.org/10.1186/1472-6947-11-38.Suche in Google Scholar

5. Loftus, J, Lindberg, A, Aydin, F, Gomez, R, Maghnie, M, Rooman, R, et al. Individualised growth response optimisation (iGRO) tool: an accessible and easy-to-use growth prediction system to enable treatment optimisation for children treated with growth hormone. J Pediatr Endocrinol Metab 2017;30:1019–28. https://doi.org/10.1515/jpem-2017-0120.Suche in Google Scholar

6. Cutfield, W, Lindberg, A, Rapaport, R, Wajnrajch, M, Saenger, P. Safety of growth hormone treatment in children born small for gestational age: the US trial and KIGS analysis. Horm Res 2006;65:153–9. https://doi.org/10.1159/000091719.Suche in Google Scholar

7. Sas, T, Mulder, P, Aanstoot, H, Houdijk, M, Jansen, M, Reeser, M, et al. Carbohydrate metabolism during long-term growth hormone treatment in children with short stature born small for gestational age. Clin Endocrinol (Oxf). 2001;54:243–51. https://doi.org/10.1046/j.1365-2265.2001.01178.x.Suche in Google Scholar

8. Sas, T, Mulder, P, Hokken-Koelega, A. Body composition, blood pressure, and lipid metabolism before and during long-term growth hormone (GH) treatment in children with short stature born small for gestational age either with or without GH deficiency. J Clin Endocrinol Metab 2000;85:3786–92. https://doi.org/10.1210/jcem.85.10.6917.Suche in Google Scholar

9. Greulich, W, Pyle, S. Radiographic Atlas of Skeletal Development of the Hand and Wrist. Stanford: Stanford University Press; 1959:p. 272.10.1097/00000441-195909000-00030Suche in Google Scholar

10. Tanner, J, Whitehouse, R, Cameron, N, Marshall, W, Healy, M, Goldstein, H. Assessment of skeletal maturity and prediction of adult height (TW2 method), 2nd ed. London: Academic Press; 1983.Suche in Google Scholar

11. Tanner, J, Goldstein, H, Whitehouse, R. Standards for children’s height at ages 2–9 years allowing for heights of parents. Arch Dis Child 1970;45:755–62. https://doi.org/10.1136/adc.45.244.755.Suche in Google Scholar

12. Carrascosa Lezcano, A, Ferrández Longás, A, Yeste Fernández, D, García-Dihinx Villanova, J, Romo Montejo, A, Copil Copil, A, et al. Spanish cross-sectional growth study 2008. Part I: weight and height values in newborns of 26-42 weeks of gestational age. An Pediatr (Barc) 2008;68:544–51. https://doi.org/10.1157/13123286.Suche in Google Scholar

13. Carrascosa Lezcano, A, Fernández García, J, Fernández Ramos, C, Fernández Longás, A, López-Siguero, J, Sánchez González, E, et al. Spanish cross-sectional growth study 2008. Part II. Height, weight and body mass index values from birth to adulthood. An Pediatr (Barc). 2008;68:552–69. https://doi.org/10.1157/13123287.Suche in Google Scholar

14. Sas, T, de Waal, W, Mulder, P, Houdijk, M, Jansen, M, Reeser, M, et al. Growth hormone treatment in children with short stature born small for gestational age: 5-year results of a randomized, double-blind, dose-response trial. J Clin Endocrinol Metab 1999;84:3064–70. https://doi.org/10.1210/jcem.84.9.5942.Suche in Google Scholar

15. Chatelain, P, Carrascosa, A, Bona, G, Fernández Longás, A, Sippell, W. Growth hormone therapy for short children born small for gestational age. Horm Res 2007;68:300–9. https://doi.org/10.1159/000107935.Suche in Google Scholar

16. Maiorana, A, Cianfarani, S. Impact of growth hormone therapy on adult height of children born small for gestational age. Pediatrics 2009;124:519. https://doi.org/10.1542/peds.2009-0293.Suche in Google Scholar

17. Hwang, I. Efficacy and safety of growth hormone treatment for children born small for gestational age. Korean J Pediatr 2014;57:379–83. https://doi.org/10.3345/kjp.2014.57.9.379.Suche in Google Scholar

18. Fejellestad-Paulsen, A, Simon, D, Czernichow, P. Short children born small for gestational age and treated with growth hormone for three years have an important catch-down five years after discontinuation of treatment. J Clin Endocrinol Metab 2004;89:1234–9. https://doi.org/10.1210/jc.2003-030962.Suche in Google Scholar

19. De Zegher, F, Maes, M, Gargosky, S, Heinrichs, C, Du Caju, M, Thiry, G, et al. High-dose growth hormone treatment of short children born small for gestational age. J Clin Endocrinol Metab 1996;81:1887–92. https://doi.org/10.1210/jc.81.5.1887.Suche in Google Scholar

20. Boguszewski, M, Lindberg, A, Wollmann, H. Three-year growth response to growth hormone treatment in very young children born small for gestational age. Data from KIGS. J Clin Endocrinol Metab 2014;99:2683–8. https://doi.org/10.1210/jc.2013-4117.Suche in Google Scholar

21. Kriström, B, Dahlgren, J, Niklasson, A, Nierop, A, Albertsson-Wikland, K. The first-year growth response to growth hormone treatment predicts the long-term prepubertal growth response in children. BMC Med Inf Decis Making 2009;9. https://doi.org/10.1186/1472-6947-9-1.Suche in Google Scholar

22. Carrascosa Lezcano, A, Audí, L, Esteban, C, Fernández-Cancio, M, Andaluz, P, Guissinyé, M, et al. Growth hormone (GH) dose, but not exon 3-deleted/full-lenth receptor polymorphism genotypes, influences growth response to two-year GH therapy in short small-for-gestational-age children. J Clin Endocrinol Metab 2008;93:147–53. https://doi.org/10.1210/jc.2007-1182.Suche in Google Scholar

23. Ranke, M, Lindberg, A, Cowell, C, Wikland, K, Reiter, E, Wilton, P, et al. Prediction of response to growth hormone treatment in short children born small for gestational age: analysis of data from KIGS (Pharmacia International Growth Database). J Clin Endocrinol Metab 2003;88:125–31. https://doi.org/10.1210/jc.2002-020867.Suche in Google Scholar

24. Dahlgren, J, Wikland, KA, Swedish Study Group for Growth Hormone Treatment. Final height in short children born small for gestational age treated with growth hormone. Pediatr Res 2005;57:216–22. https://doi.org/10.1203/01.pdr.0000148716.71231.81.Suche in Google Scholar

25. Arends, N, Boonstra, V, Mulder, P, Odink, R, Stokvis-Brantsma, W, Rongen-Westerlaken, C, et al. GH treatment and its effect on bone mineral density, bone maturation and growth in short children born small for gestational age: 3-year results of a randomized, controlled GH trial. Clin Endocrinol (Oxf) 2003;59:779–87. https://doi.org/10.1046/j.1365-2265.2003.01905.x.Suche in Google Scholar

26. Horikawa, R, Tanaka, T, Nishinaga, H, Ogawa, Y, Yokoya, S. Evaluation of growth hormone treatment efficacy in short Japanese children born small for gestational age: five-year treatment outcome and impact on puberty. Clin Pediatr Endocrinol 2017;26:63–72. https://doi.org/10.1297/cpe.26.63.Suche in Google Scholar

27. Coutant, R, Carel, J, Letrait, M, Bouvattier, C, Chatelain, P, Coste, J, et al. Short stature associated with intrauterine growth retardation: final height of untreated and growth hormone-treated children. J Clin Endocrinol Metab 1998;83:1070–4. https://doi.org/10.1210/jcem.83.4.4750.Suche in Google Scholar

28. Ranke, MAL. Growth hormone treatment of short children born small for gestational age or with Silver-Russell syndrome: results from KIGS (Kabi International Growth Study), including the first report on final height. Acta Paediatr Suppl 1996;417:18–26. https://doi.org/10.1111/j.1651-2227.1996.tb14288.x.Suche in Google Scholar

29. Zucchini, S, Cacciari, E, Balsamo, A, Cicognani, A, Tassinari, D, Barbieri, E, et al. Final height of short subjects of low birth weight with and without growth hormone treatment. Arch Dis Child 2001;84:340–3. https://doi.org/10.1136/adc.84.4.340.Suche in Google Scholar

30. Van Pareren, Y, Mulder, P, Houdijk, M, Jansen, M, Reeser, M, Hokken-Koelega, A. Adult height after long-term, continuous growth hormone (GH) treatment in short children born small for gestational age: results of a randomized, double-blind, dose-response GH trial. J Clin Endocrinol Metab 2003;88:3584–90. https://doi.org/10.1210/jc.2002-021172.Suche in Google Scholar

31. De Zegher, F, Du Caju, M, Heinrichs, C, Maes, M, De Schepper, J, Craen, M, et al. Early, discontinous, high dose growth hormone treatment to normalize height and weight of short children born small for gestational age: results over 6 years. J Clin Endocrinol Metab 1999;84:1558–61. https://doi.org/10.1210/jcem.84.5.5697.Suche in Google Scholar

32. Ranke, M, Lindberg, A. Height at start, first-year growth response and cause of shortness at birth are major determinants of adult height outcomes of short children born small for gestational age and Silver-Russell syndrome treated with growth hormone: analysis of data from KIGS. Horm Res Paediatr 2010;74:259–66. https://doi.org/10.1159/000289570.Suche in Google Scholar

33. Reiter, E, Price, D, Wilton, P, Albertsson-Wikland, K, Ranke, M. Effect of growth hormone (GH) treatment on the near-final height of 1258 patients with idiopathic GH deficiency: analysis of a large international database. J Clin Endocrinol Metab 2006;91:2047–54. https://doi.org/10.1210/jc.2005-2284.Suche in Google Scholar

34. Ranke, M, Lindberg, A, Price, D, Darendeliler, F, Albertsson-Wikland, K, Wilton, P, et al. Age at growth hormone therapy start and first-year responsiveness to growth hormone are major determinants of height outcome in idiopathic short stature. Horm Res 2007;68:53–62. https://doi.org/10.1159/000098707.Suche in Google Scholar

35. van Pareren, Y, Mulder, P, Houdijk, M, Jansen, M, Reeser, M, Hokken-Koelega, A. Effect of discontinuation of growth hormone treatment on risk factors for cardiovascular disease in adolescents born small for gestational age. J Clin Endocrinol Metab 2003;88:347–53. https://doi.org/10.1210/jc.2002-020458.Suche in Google Scholar

36. Van Dijk, M, Bannik, E, Van Pareren, Y, Mulder, P, Hokken-Koelega, A. Risk factors for diabetes mellitus type 2 and metabolic syndrome are comparable for previously growth hormone-treated young adults born small for gestational age (SGA) and untreated short SGA controls. J Clin Endocrinol Metab 2007;92:160–5. https://doi.org/10.1210/jc.2006-1073.Suche in Google Scholar

37. Rodriguez Arnao, MD, Rodriguez Sanchez, A, Diez Lopez, I, Ramirez Fernandez, J, Bermudez de la Vega, JA, Yeste Fernandez, D, et al. Adherence and long-term outcomes of growth hormone therapy with easypod in pediatric subjects: Spanish ECOS study. Endocr Connect 2019;8:1240–9. https://doi.org/10.1530/ec-19-0325.Suche in Google Scholar

38. Oyarzabal, M, Aliaga, M, Chueca, M, Echarte, G, Ulied, A. Multicentre survey on compliance with growth hormone therapy: what can be improved?. Acta Paediatr 1998;87: 387–91. https://doi.org/10.1111/j.1651-2227.1998.tb01464.x.Suche in Google Scholar

Received: 2019-09-18
Accepted: 2020-03-30
Published Online: 2020-07-05
Published in Print: 2020-07-28

© 2020 Walter de Gruyter GmbH, Berlin/Boston

Artikel in diesem Heft

  1. Frontmatter
  2. Review Articles
  3. Definition and early diagnosis of metabolic syndrome in children
  4. Cystic fibrosis-related diabetes: an update on pathophysiology, diagnosis, and treatment
  5. Original Articles
  6. Association of sleep characteristics with adiposity markers in children
  7. Prevalence of abdominal obesity in non-obese adolescents: a North Indian adolescent study
  8. Utility of estimated glucose disposal rate for predicting metabolic syndrome in children and adolescents with type-1 diabetes
  9. Continuous glucose monitoring reduces pubertal hyperglycemia of type 1 diabetes
  10. Association between eating behavior, anthropometric and biochemical measurements, and peptide YY (PYY) hormone levels in obese adolescents in outpatient care
  11. Autoimmune hyperthyroidism in children & adolescents in Sudan: a 13 years’ experience of a Paediatric Endocrinology Clinic
  12. Timing, prevalence, and dynamics of thyroid disorders in children and adolescents affected with Down syndrome
  13. Assessment of the most common CYP21A2 point mutations in a cohort of congenital adrenal hyperplasia patients from Egypt
  14. Quality of life and associated factors in parents of children with late diagnosed phenylketonuria. A cross sectional study in a developing country (Tunisia)
  15. Genetic analysis and long-term treatment monitoring of 11 children with glycogen storage disease type IIIa
  16. Growth and metabolic effects of long-term recombinant human growth hormone (rhGH) treatment in short children born small for gestational age: GH-RAST study
  17. Menstrual cycle, reproductive function, body mass index, and metabolic profiles of women with former central precocious puberty: 10–20-year longitudinal cohort study in southern Thailand
  18. Letter to the Editors
  19. European Society of Paediatric Radiology (ESPR) Child Abuse Taskforce Committee: a response to Miller et al.
  20. The correct formula to calculate triglyceride-glucose index (TyG)
  21. Case Reports
  22. Octreotide-related exocrine pancreatic insufficiency (EPI) in congenital hyperinsulinism
  23. Improvement in glycaemic parameters using SGLT-2 inhibitor and GLP-1 agonist in combination in an adolescent with diabetes mellitus and Prader-Willi syndrome: a case report
  24. Three patients with glucose-6 phosphatase catalytic subunit 3 deficiency
  25. Efficacy and safety of denosumab treatment in a prepubertal patient with cherubism
https://doi.org/10.1515/jpem-2019-0438
Schlagwörter für diesen Artikel
growth hormone; height; small for gestational age; somatropin metabolism

Artikel in diesem Heft

  1. Frontmatter
  2. Review Articles
  3. Definition and early diagnosis of metabolic syndrome in children
  4. Cystic fibrosis-related diabetes: an update on pathophysiology, diagnosis, and treatment
  5. Original Articles
  6. Association of sleep characteristics with adiposity markers in children
  7. Prevalence of abdominal obesity in non-obese adolescents: a North Indian adolescent study
  8. Utility of estimated glucose disposal rate for predicting metabolic syndrome in children and adolescents with type-1 diabetes
  9. Continuous glucose monitoring reduces pubertal hyperglycemia of type 1 diabetes
  10. Association between eating behavior, anthropometric and biochemical measurements, and peptide YY (PYY) hormone levels in obese adolescents in outpatient care
  11. Autoimmune hyperthyroidism in children & adolescents in Sudan: a 13 years’ experience of a Paediatric Endocrinology Clinic
  12. Timing, prevalence, and dynamics of thyroid disorders in children and adolescents affected with Down syndrome
  13. Assessment of the most common CYP21A2 point mutations in a cohort of congenital adrenal hyperplasia patients from Egypt
  14. Quality of life and associated factors in parents of children with late diagnosed phenylketonuria. A cross sectional study in a developing country (Tunisia)
  15. Genetic analysis and long-term treatment monitoring of 11 children with glycogen storage disease type IIIa
  16. Growth and metabolic effects of long-term recombinant human growth hormone (rhGH) treatment in short children born small for gestational age: GH-RAST study
  17. Menstrual cycle, reproductive function, body mass index, and metabolic profiles of women with former central precocious puberty: 10–20-year longitudinal cohort study in southern Thailand
  18. Letter to the Editors
  19. European Society of Paediatric Radiology (ESPR) Child Abuse Taskforce Committee: a response to Miller et al.
  20. The correct formula to calculate triglyceride-glucose index (TyG)
  21. Case Reports
  22. Octreotide-related exocrine pancreatic insufficiency (EPI) in congenital hyperinsulinism
  23. Improvement in glycaemic parameters using SGLT-2 inhibitor and GLP-1 agonist in combination in an adolescent with diabetes mellitus and Prader-Willi syndrome: a case report
  24. Three patients with glucose-6 phosphatase catalytic subunit 3 deficiency
  25. Efficacy and safety of denosumab treatment in a prepubertal patient with cherubism
Jetzt anmelden und 20% sparen
Institutioneller Zugang
Wie funktioniert Authentifizierung?
Haben Sie eine Idee, wie wir unsere Website verbessern können?
Bitte schreiben Sie uns.
© 2025 De Gruyter Brill
Heruntergeladen am 17.9.2025 von https://www.degruyterbrill.com/document/doi/10.1515/jpem-2019-0438/html
Button zum nach oben scrollen