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Combined therapy with GnRH analogue and growth hormone increases adult height in children with short stature and normal pubertal onset

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Abstract

Objective

To investigate whether gonadotropin releasing hormone analogue (GnRHa) combined with recombinant human growth hormone (rhGH) can improve the adult height (AHt) of children with short stature and normal pubertal onset.

Methods

In this retrospective study, GnRHa/rhGH treatment was given to children with normal pubertal onset and short stature. Patients were followed up to measure their AHt. The primary outcomes were the disparity between AHt standard deviation score (AHt SDS) and pre-treatment height standard deviation score (Ht SDS) and the disparity between AHt and target height (THt).

Results

A total of 94 patients were included. Forty-nine boys were treated with GnRHa/rhGH for 24.84 ± 13.01 months, and 45 girls were treated for 23.89 ± 10.43 months. (2) Before treatment, the Ht SDS of boys and girls was −1.82 ± 1.30 and −1.10 ± 1.61, respectively, and the target height was 168.98 ± 3.51 cm and 157.90 ± 3.25 cm, respectively. (3) After treatment, for boys, the AHt SDS increased by 1.37 ± 1.28 (p = 0.000) and the disparity between AHt and THt was 0.98 ± 6.18 cm (p = 0.273); for girls, the AHtSDS increased by 1.28 ± 1.48 (p = 0.000), and the disparity between AHt and THt was 3.64 ± 4.86 cm (n = 45, p = 0.000). (4) Subgroup analysis showed that, for boys with idiopathic short stature (ISS) and non-ISS, AHt SDS increased by 2.00 ± 1.16 (p = 0.000) and 0.71 ± 1.06 (p = 0.003) respectively, compared with the pre-treatment HtSDS; The disparities between AHt and THt were −0.70 ± 6.54 cm and 2.73 ± 5.37 cm respectively. For girls with ISS and non-ISS, AHtSDS increased by 2.73 ± 1.21 (p = 0.000) and 0.748 ± 1.19 (p = 0.001), respectively; AHt increased by 2.63 ± 6.12 cm (p = 0.165) and 4.02 ± 4.37 cm (p = 0.000) compared with THt, respectively. (5) Multiple linear regression analysis showed that the baseline bone age (BA) (β = −0.200, p = 0.003), basal IGF-1(β = −0.002, p = 0.008) and HtSDS (β = −0.679, p = 0.000) had negative effects on increment of AHtSDS.

Conclusion

For adolescents with normal pubertal onset and short stature, with or without ISS, GnRHa/rhGH therapy can effectively improve AHtSDS. After treatment, ISS adolescents can reach the THts, and Non-ISS adolescents can exceed their THts.

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Funding

This study was funded by the National Key Research and Development Program of China (2016YFC0905102, 2016YFA0101003), CAMS Innovation Fund for Medical Sciences (CIFMS) (2016-I2M-1-002, 2017-I2M-3-007), and the Project of National Natural Science Foundation of China (81771576).

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  1. These authors contributed equally: Li Shuying, Wang Xi

Authors and Affiliations

  1. Division of Endocrinology, Peking Union Medical College Hospital, Beijing, 100730, China

    Shuying Li, Xi Wang, Yaling Zhao, Wen Ji, Jiangfeng Mao, Min Nie & Xueyan Wu

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  1. Shuying Li
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  2. Xi Wang
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  3. Yaling Zhao
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Correspondence to Jiangfeng Mao or Xueyan Wu.

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Li, S., Wang, X., Zhao, Y. et al. Combined therapy with GnRH analogue and growth hormone increases adult height in children with short stature and normal pubertal onset. Endocrine 69, 615–624 (2020). https://doi.org/10.1007/s12020-020-02375-5

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