Early-onset growth hormone treatment in Prader–Willi syndrome attenuates transition to severe obesity
-
Aneta Kodytková
, Shenali Anne Amaratunga
, Eva El-Lababidi
, Ivana Čermáková
, Jana Černá
, Marcela Dvořáková
, Božena Kalvachová, Stanislava Koloušková
, Ivana Kotvalová
, Olga Magnová
, David Neumann
, Dana Novotná
, Barbora Obermannová
, Renata Pomahačová
, Štěpánka Průhová
, Jiří Strnadel
, Jaroslav Škvor
, Marta Šnajderová
, Zdeněk Šumník
, Jirina Zapletalová
, Daniela Zemková
, Kateřina Kusalová
, Jiří Šilar
und Jan Lebl
Abstract
Objectives
Subsequent to early life feeding issues, children with Prader–Willi syndrome (PWS) develop hyperphagia and severe obesity. Growth hormone (GH) therapy has been approved in PWS to improve growth, body composition, and BMI. We aimed to clarify the role of age at GH therapy onset on growth and BMI trajectories in children with PWS.
Methods
We analyzed height and BMI in 114 patients (58 boys) from REPAR – Czech national GH registry. From them, 69 started GH therapy prior to 2 y/o (age 0.8 ± 0.4 years; mean ± SD; early-onset group [EO]), and 45 later (age 7.1 ± 4.1 years; late-onset group [LO]).
Results
Height-SDS before therapy was similar in all (EO: −1.9 ± 1.2 [mean ± SD]; LO: −1.7 ± 1.1). After the first year of GH therapy, height-SDS in the EO group increased to −1.0 ± 1.2, in the LO group to −0.9 ± 1.1. After 5 years, height fully normalized in all (−0.1 ± 1.1 SDS). The LO children were already obese at treatment initiation (BMI-SDS: 2.9 ± 2.2), and their BMI-SDS decreased after 1 year of GH therapy by 0.9 (p=0.003). The weight in EO children was below average before GH treatment (BMI-SDS: −0.9 ± 1.2) and their BMI-SDS increased to the overweight range of 1.3 ± 2.2 (p<0.001) within the oncoming 3 years. Albeit BMI-SDS was around the obesity limit in most children after 5 years on GH therapy, the highest lifetime BMI-SDS was lower in EO (2.2 ± 2.6) than in LO (3.7 ± 2.2; p<0.001).
Conclusions
GH treatment in PWS normalizes body height. After 5 years of GH therapy, BMI-SDS in EO and LO groups are similar; however, the EO group is exposed to lower maximal BMI-SDS values.
-
Research ethics: This study was approved by the Multicentric Ethics Committee at the Olomouc University Hospital, Palacky University (date of approval: 11th November 2013; 138/13 MEK 24). The research was conducted ethically in accordance with the World Medical Association Declaration of Helsinki.
-
Informed consent: Patients and their legal guardians gave their written consent to collect and to further analyze their anonymized data on GH therapy within the REPAR database.
-
Author contributions: The authors have accepted responsibility for the entire content of this manuscript and approved its submission.
-
Use of Large Language Models, AI and Machine Learning Tools: None declared.
-
Conflict of interest: The authors state no conflict of interest.
-
Research funding: None declared.
-
Data availability: Not applicable.
References
1. Angulo, MA, Butler, MG, Cataletto, ME. Prader-Willi syndrome: a review of clinical, genetic, and endocrine findings. J Endocrinol Investig 2015;38:1249–63. https://doi.org/10.1007/s40618-015-0312-9.Suche in Google Scholar PubMed PubMed Central
2. Manzardo, AM, Weisensel, N, Ayala, S, Hossain, W, Butler, MG. Prader-Willi syndrome genetic subtypes and clinical neuropsychiatric diagnoses in residential care adults. Clin Genet 2018;93:622–31. https://doi.org/10.1111/cge.13142.Suche in Google Scholar PubMed PubMed Central
3. Cassidy, SB, Schwartz, S, Miller, JL, Driscoll, DJ. Prader-Willi syndrome. Genet Med 2012;14:10–26. https://doi.org/10.1038/gim.0b013e31822bead0.Suche in Google Scholar PubMed
4. Ranke, MB, Wit, JM. Growth hormone – past, present and future. Nat Rev Endocrinol 2018;14:285–300. https://doi.org/10.1038/nrendo.2018.22.Suche in Google Scholar PubMed
5. Burman, P, Ritzén, EM, Lindgren, AC. Endocrine dysfunction in Prader-Willi syndrome: a review with special reference to GH. Endocr Rev 2001;22:787–99. https://doi.org/10.1210/edrv.22.6.0447.Suche in Google Scholar PubMed
6. Deal, CL, Tony, M, Höybye, C, Allen, DB, Tauber, M, Christiansen, JS. Growth hormone research society workshop summary: consensus guidelines for recombinant human growth hormone therapy in prader-willi syndrome. J Clin Endocrinol Metab 2013;98:E1072–87. https://doi.org/10.1210/jc.2012-3888.Suche in Google Scholar PubMed PubMed Central
7. Takeda, A, Cooper, K, Bird, A, Baxter, L, Frampton, G, Gospodarevskaya, E, et al.. Recombinant human growth hormone for the treatment of growth disorders in children: a systematic review and economic evaluation. Health Technol Assess 2010;14:1–209. https://doi.org/10.3310/hta14420.Suche in Google Scholar PubMed
8. Angulo, MA, Castr-Magana, M, Lamerson, M, Arguello, R, Accacha, S, Khan, A. Final adult height in children with prader–willi syndrome with and without human growth hormone treatment. Am J Med Genet 2007;143A:1456–61.10.1002/ajmg.a.31824Suche in Google Scholar PubMed
9. Lindgren, AC, Lindberg, A. Growth hormone treatment completely normalizes adult height and improves body composition in Prader-Willi syndrome: experience from KIGS (Pfizer international growth database). Horm Res 2008;70:182–7. https://doi.org/10.1159/000145019.Suche in Google Scholar PubMed
10. Bakker, NE, Lindberg, A, Heissler, J, Wollmann, HSCA, Camacho-Hübner, C, Hokken-Koelega, AC. Growth hormone treatment in children with prader-willi syndrome: three years of longitudinal data in prepubertal children and adult height data from the KIGS database. J Clin Endocrinol Metab 2017;102:1702–11. https://doi.org/10.1210/jc.2016-2962.Suche in Google Scholar PubMed
11. Festen, DAM, De Lind Van Wijngaarden, R, Van Eekelen, M, Otten, BJ, Wit, JM, Duivenvoorden, HJ, et al.. Randomized controlled GH trial: effects on anthropometry, body composition and body proportions in a large group of children with Prader-Willi syndrome. Clin Endocrinol 2008;69:443–51. https://doi.org/10.1111/j.1365-2265.2008.03228.x.Suche in Google Scholar PubMed
12. Donze, SH, Damen, L, Mahabier, EF, Hokken-Koelega, ACS. Cognitive functioning in children with Prader-Willi syndrome during 8 years of growth hormone treatment. Eur J Endocrinol 2020;182:405–11. https://doi.org/10.1530/eje-19-0479.Suche in Google Scholar
13. Luo, Y, Zheng, Z, Yang, Y, Bai, X, Yang, H, Zhu, H, et al.. Effects of growth hormone on cognitive, motor, and behavioral development in Prader-Willi syndrome children: a meta-analysis of randomized controlled trials. Endocrine 2021;71:321–30. https://doi.org/10.1007/s12020-020-02547-3.Suche in Google Scholar PubMed
14. Lecka-Ambroziak, A, Wysocka-Mincewicz, M, Doleżal-Ołtarzewska, K, Zygmunt-Górska, A, Wędrychowicz, A, Żak, T, et al.. Effects of recombinant human growth hormone treatment, depending on the therapy start in different nutritional phases in paediatric patients with prader–willi syndrome: a polish multicentre study. J Clin Med 2021;10:1–19. https://doi.org/10.3390/jcm10143176.Suche in Google Scholar PubMed PubMed Central
15. Gao, Y, Yang, LL, Dai, YL, Shen, Z, Zhou, Q, Zou, CC. Effects of early recombinant human growth hormone treatment in young Chinese children with Prader–Willi syndrome. Orphanet J Rare Dis 2023;18:1–10. https://doi.org/10.1186/s13023-023-02615-7.Suche in Google Scholar PubMed PubMed Central
16. Corripio, R, Tubau, C, Calvo, L, Brun, C, Capdevila, N, Larramona, H, et al.. Safety and effectiveness of growth hormone therapy in infants with Prader-Willi syndrome younger than 2 years: a prospective study. J Pediatr Endocrinol Metab 2019;32:879–84. https://doi.org/10.1515/jpem-2018-0539.Suche in Google Scholar PubMed
17. Kodytková, A, Al Lababidi, E, Čermáková, I, Černá, J, Čížek, J, Kalvachová, B, et al.. Analýza dat z celostátního registru pacientů léčených růstovým hormonem REPAR. Česko-Slovenská Pediatr 2020;75:205–12.Suche in Google Scholar
18. Kodytková, A, Zemková, D, Koloušková, S, Lebl, J. Růstové databáze a registry – cesta k poznání fyziologických účinků růstového hormonu. Česko-Slovenská Pediatr 2020;75:251–5.Suche in Google Scholar
19. Hughes, IP, Harris, M, Cotterill, A, Ambler, G, Cowell, CT, Cutfield, WS, et al.. Comparison of weight- vs body surface area-based growth hormone dosing for children: implications for response. Clin Endocrinol 2014;80:384–94. https://doi.org/10.1111/cen.12315.Suche in Google Scholar PubMed
20. Bláha, P, Hrušková, M, Krejčovský, L, Al, E. Growth and development of Czech children aged from birth to six years: Anthropological research 2001–2003. Prague: Charles University; 2010.Suche in Google Scholar
21. Grootjen, LN, Trueba-Timmermans, DJ, Damen, L, Mahabier, EF, Kerkhof, GF, Hokken-Koelega, ACS. Long-term growth hormone treatment of children with PWS: the earlier the start, the better the outcomes? J Clin Med 2022;11. https://doi.org/10.3390/jcm11092496.Suche in Google Scholar PubMed PubMed Central
22. Wolfgram, PM, Carrel, AL, Allen, DB. Long-term effects of recombinant human growth hormone therapy in children with Prader-Willi syndrome. Curr Opin Pediatr 2013;25:509–14. https://doi.org/10.1097/mop.0b013e328362c7a2.Suche in Google Scholar
23. Bakker, NE, Kuppens, RJ, Siemensma, EPC, Tummers De Lind Van Wijngaarden, RFA, Festen, DAM, Bindels-De Heus, GCB, et al.. Eight years of growth hormone treatment in children with prader-willi syndrome: maintaining the positive effects. J Clin Endocrinol Metab 2013;98:4013–22. https://doi.org/10.1210/jc.2013-2012.Suche in Google Scholar PubMed
24. Group WHO Multicentre Growth Reference Study. WHO Child Growth Standards: length/height-for-age, weight-for-age, weight-for-length, weight-for-height and body mass index-for-age: methods and development. Geneva: World Health Organization; 2006.Suche in Google Scholar
25. Brambilla, P, Crinò, A, Bedogni, G, Bosio, L, Cappa, M, Corrias, A, et al.. Metabolic syndrome in children with Prader-Willi syndrome: the effect of obesity. Nutr Metabol Cardiovasc Dis 2011;21:269–76. https://doi.org/10.1016/j.numecd.2009.10.004.Suche in Google Scholar PubMed
26. O’Neill, S, O’Driscoll, L. Metabolic syndrome: a closer look at the growing epidemic and its associated pathologies. Obes Rev 2015;16:1–12. https://doi.org/10.1111/obr.12229.Suche in Google Scholar PubMed
27. Goldstone, AP, Holland, AJ, Hauffa, BP, Hokken-Koelega, AC, Tauber, M. Recommendations for the diagnosis and management of Prader-Willi syndrome. J Clin Endocrinol Metab 2008;93:4183–97. https://doi.org/10.1210/jc.2008-0649.Suche in Google Scholar PubMed
28. Maniatis, AK, Carakushansky, M, Galcheva, S, Prakasam, G, Fox, LA, Dankovcikova, A, et al.. Treatment burden of weekly somatrogon vs daily somatropin in children with growth hormone deficiency: a randomized study. J Endocr Soc 2022;6:1–10. https://doi.org/10.1210/jendso/bvac117.Suche in Google Scholar PubMed PubMed Central
29. Freedman, DS, Butte, NF, Taveras, EM, Lundeen, EA, Blanck, HM, Goodman, AB, et al.. BMI z-Scores are a poor indicator of adiposity among 2- to 19-year-olds with very high BMIs, NHANES 1999-2000 to 2013-2014. Obesity 2017;25:739–46. https://doi.org/10.1002/oby.21782.Suche in Google Scholar PubMed PubMed Central
© 2025 Walter de Gruyter GmbH, Berlin/Boston
Artikel in diesem Heft
- Frontmatter
- Review
- A recent update on childhood obesity: aetiology, treatment and complications
- Original Articles
- Chronotype, sleep, and glycemic control in children and adolescents with type 1 diabetes: a case-control study
- Determinants of childhood and adolescent obesity and it’s effect on metabolism in South Indian population
- Evaluation of continuous glucose monitoring and nutritional status in glycogen storage diseases
- Retrospective assessment of hepatic involvement in patients with inherited metabolic disorders: nine-year single-center experience
- Relationships among biological sex, body composition, and bone mineral density in young persons with and without diabetes
- The clinical characteristics of 10 cases and adult height of six cases of rare familial male-limited precocious puberty
- Optimal timing of repeat thyroid fine-needle aspiration biopsy
- Medium-chain acyl-CoA dehydrogenase deficiency in North Macedonia – ten years experience
- The effect of antenatal steroids on metabolic bone disease of prematurity
- Prader-Willi syndrome gene expression profiling of obese and non-obese patients reveals transcriptional changes in CLEC4D and ANXA3
- Early-onset growth hormone treatment in Prader–Willi syndrome attenuates transition to severe obesity
- Case Reports
- Neonatal severe hyperparathyroidism with inactivating calcium sensing receptor (CaSR) mutation (p.I81K)
- Clinical manifestations and molecular genetics of seven patients with Niemann–Pick type-C: a case series with a novel variant
- Expanding the genotypic spectrum of 3β-hydroxy-δ5-C27-steroid dehydrogenase (HSD3B7) deficiency: novel mutations and clinical outcomes
Artikel in diesem Heft
- Frontmatter
- Review
- A recent update on childhood obesity: aetiology, treatment and complications
- Original Articles
- Chronotype, sleep, and glycemic control in children and adolescents with type 1 diabetes: a case-control study
- Determinants of childhood and adolescent obesity and it’s effect on metabolism in South Indian population
- Evaluation of continuous glucose monitoring and nutritional status in glycogen storage diseases
- Retrospective assessment of hepatic involvement in patients with inherited metabolic disorders: nine-year single-center experience
- Relationships among biological sex, body composition, and bone mineral density in young persons with and without diabetes
- The clinical characteristics of 10 cases and adult height of six cases of rare familial male-limited precocious puberty
- Optimal timing of repeat thyroid fine-needle aspiration biopsy
- Medium-chain acyl-CoA dehydrogenase deficiency in North Macedonia – ten years experience
- The effect of antenatal steroids on metabolic bone disease of prematurity
- Prader-Willi syndrome gene expression profiling of obese and non-obese patients reveals transcriptional changes in CLEC4D and ANXA3
- Early-onset growth hormone treatment in Prader–Willi syndrome attenuates transition to severe obesity
- Case Reports
- Neonatal severe hyperparathyroidism with inactivating calcium sensing receptor (CaSR) mutation (p.I81K)
- Clinical manifestations and molecular genetics of seven patients with Niemann–Pick type-C: a case series with a novel variant
- Expanding the genotypic spectrum of 3β-hydroxy-δ5-C27-steroid dehydrogenase (HSD3B7) deficiency: novel mutations and clinical outcomes