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A randomised controlled trial evaluating IGF-I titration in contrast to current GH dosing strategies in children born Small for Gestational Age (NESGAS).

Jensen, Rikke Beck; Thankamony, Ajay; O'Connell, Susan M; Kirk, Jeremy M W; Donaldson, Malcolm; Ivarsson, Sten LU ; Soder, Olle; Roche, Edna; Hoey, Hilary and Dunger, David P, et al. (2014) In European Journal of Endocrinology 171(4). p.509-518
Abstract
Background: Short children born small for gestational age (SGA) are treated with growth hormone (GH) dose based on body size, but treatment may lead to high levels of IGF-I. The objective was to evaluate IGF-I titration of GH dose in contrast to current dosing strategies. Methods: In the North European Small for gestational age study (NESGAS) 92 short pre-pubertal children born SGA were randomised after one year of high dose GH treatment (67µg/kg/day) to three different regimens: high-dose (67µg/kg/day), low-dose (35µg/kg/day) or IGF-I titration. Results: The average dose during the second year of the randomised trial did not differ between the IGF-I titration group (38µg/kg/day, SD 0.019) and the low-dose group (35µg/kg/day, SD 0.002)... (More)
Background: Short children born small for gestational age (SGA) are treated with growth hormone (GH) dose based on body size, but treatment may lead to high levels of IGF-I. The objective was to evaluate IGF-I titration of GH dose in contrast to current dosing strategies. Methods: In the North European Small for gestational age study (NESGAS) 92 short pre-pubertal children born SGA were randomised after one year of high dose GH treatment (67µg/kg/day) to three different regimens: high-dose (67µg/kg/day), low-dose (35µg/kg/day) or IGF-I titration. Results: The average dose during the second year of the randomised trial did not differ between the IGF-I titration group (38µg/kg/day, SD 0.019) and the low-dose group (35µg/kg/day, SD 0.002) (P=0•46), but there was a wide variation in the IGF-I titration group (range 10-80µg/kg/day). The IGF-I titration group had significantly lower height gain (0.17SDS, SD 0.18) during the second year of the randomised trial compared to the high-dose group (0.46SDS, SD 0.25) but not significantly lower than the low-dose group (0.23SDS, SD 0.15) (p=0.17). The IGF-I titration group had lower IGF-I levels after two years of the trial (mean 1.16, SD 1.24) compared to both the low-dose (mean 1.76, SD 1.48) and the high-dose (mean 2.97, SD 1.63) groups. Conclusion: IGF-I titration of GH dose in SGA children proved less effective than current dosing strategies. IGF-I titration resulted in physiological IGF-I levels with a wide range of GH dose and a poorer growth response, which indicates the role of IGF-I resistance and highlights the heterogeneity of short SGA children. (Less)
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European Journal of Endocrinology
volume
171
issue
4
pages
509 - 518
publisher
Society of the European Journal of Endocrinology
external identifiers
  • pmid:25080293
  • wos:000343671500016
  • scopus:84907207473
ISSN
1479-683X
DOI
10.1530/EJE-14-0419
language
English
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yes
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0b59b57c-4070-45cc-98ab-71edbf3ad875 (old id 4615800)
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http://www.ncbi.nlm.nih.gov/pubmed/25080293?dopt=Abstract
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2014-09-03 18:02:26
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2017-07-30 03:03:25
@article{0b59b57c-4070-45cc-98ab-71edbf3ad875,
  abstract     = {Background: Short children born small for gestational age (SGA) are treated with growth hormone (GH) dose based on body size, but treatment may lead to high levels of IGF-I. The objective was to evaluate IGF-I titration of GH dose in contrast to current dosing strategies. Methods: In the North European Small for gestational age study (NESGAS) 92 short pre-pubertal children born SGA were randomised after one year of high dose GH treatment (67µg/kg/day) to three different regimens: high-dose (67µg/kg/day), low-dose (35µg/kg/day) or IGF-I titration. Results: The average dose during the second year of the randomised trial did not differ between the IGF-I titration group (38µg/kg/day, SD 0.019) and the low-dose group (35µg/kg/day, SD 0.002) (P=0•46), but there was a wide variation in the IGF-I titration group (range 10-80µg/kg/day). The IGF-I titration group had significantly lower height gain (0.17SDS, SD 0.18) during the second year of the randomised trial compared to the high-dose group (0.46SDS, SD 0.25) but not significantly lower than the low-dose group (0.23SDS, SD 0.15) (p=0.17). The IGF-I titration group had lower IGF-I levels after two years of the trial (mean 1.16, SD 1.24) compared to both the low-dose (mean 1.76, SD 1.48) and the high-dose (mean 2.97, SD 1.63) groups. Conclusion: IGF-I titration of GH dose in SGA children proved less effective than current dosing strategies. IGF-I titration resulted in physiological IGF-I levels with a wide range of GH dose and a poorer growth response, which indicates the role of IGF-I resistance and highlights the heterogeneity of short SGA children.},
  author       = {Jensen, Rikke Beck and Thankamony, Ajay and O'Connell, Susan M and Kirk, Jeremy M W and Donaldson, Malcolm and Ivarsson, Sten and Soder, Olle and Roche, Edna and Hoey, Hilary and Dunger, David P and Juul, Anders},
  issn         = {1479-683X},
  language     = {eng},
  number       = {4},
  pages        = {509--518},
  publisher    = {Society of the European Journal of Endocrinology},
  series       = {European Journal of Endocrinology},
  title        = {A randomised controlled trial evaluating IGF-I titration in contrast to current GH dosing strategies in children born Small for Gestational Age (NESGAS).},
  url          = {http://dx.doi.org/10.1530/EJE-14-0419},
  volume       = {171},
  year         = {2014},
}