조기 사춘기 여아에서 단기간 성선자극호르몬 방출호르몬 효능약제와 성장호르몬 병합투여의 성장촉진 효과 = Growth promoting effect of short-term gonadotropin releasing hormone agonist with or without growth hormone in girls with early puberty

다국어 초록 (Multilingual Abstract)

Purpose : The hope that arresting pubertal developement might increase final adult height has led to an attempt to use GnRH agonist (GnRHa) in children with early puberty and poor growth prognosis. We investigated the growth-promoting effect of GnRH agonists with or without growth hormone (GH) in girls with early puberty and decreased predicted adult height (PAH).
Methods : Thirty five girls with advanced bone age and early pubertal signs were randomized for treatment for about 1 year with monthly GnRHa in group 1 (n=18), or with a combination of GH and GnRHa in group 2 (n=17). The following growth parameters were compared between groups, and the difference (Δ) before and after treatment : chronological age (CA), bone age (BA), Δ(BA-CA), height (HT), target height (TH), predicted adult height (PAH), Δ (TH-PAH), serum insulin-like growth factor (IGF-1) and insulin-like growth factor binding protein (IGFBP-3).
Results : Before treatment, BA, TH, PAH Standard deviation scores (SDS), Δ(TH-PAH) were not different between the two groups, but CA was higher in group 2 and Δ(BA-CA) were higher in group 1 (P<0.05). After 1.06±0.93 year of treatment, Δ (BA-CA) decreased and there were significant changes in PAH and Δ (TH-PAH), especially in group 2 (P<0.05 in group 1, and P<0.001 in group 2). In both groups, IGF-1 and IGFBP-3 were not different before and after treatment, but after treatment, IGF-1 level in group 2 was marginally higher than IGF-1 in group 1 (P<0.1).
Conclusion : Compromised predicted adult height in girls with early puberty and advanced bone age was significantly improved with GnRH with/without GH treatment in the short-term period. The addition of GH to GnRHa results in a significant increase in PAH compared to GnRHa alone because GnRHa suppressed growth hormone-IGF-1 axis. For comparison of final adult height, further longitudinal follow-up will be needed.

국문 초록 (Abstract)

목 적 : 성조숙증에서 관찰된 최근의 연구 결과를 보면 사춘기 발육이 빠른 당시에는 신장이 커보일 수 있으나 결국 최종성인신장은 감소하게 된다. 이에 사춘기를 중단시킴으로써 최종 성인신장을 증가시킬 수 있을 것이라는 기대로 성선자극호르몬 방출호르몬 효능약제를 사용하여 골성숙의 기간을 연장하고자 하였다. 또한 조기 사춘기로 인하여 최종성인신장의 예후가 불량한 소아에서 성선자극호르몬 방출호르몬 효능약제 및 성장호르몬의 병합요법 효과를 성선자극호르몬 방출호르몬 효능약제 단독 사용 시의 효과와 비교하여 각각의 성장 촉진 효과를 알아보고자 하였다.
방 법 : 역연령에 비하여 골연령이 증가되어 있으며 조기 사춘기를 보이는 여아를 대상으로 GnRHa 및 성장호르몬을 단기간 투여하였다. 제 1군은 triptorelin을 단독으로 4주에 한 번씩 근육주사하였고, 제 2군은 성장호르몬을 병합하여 치료하였다. 치료 기간은 약 1년이었으며 치료 시작시와 치료 후의 두 군간의 역연령, 골연령, 역연령과 골연령의 차이, 예측성인신장, 표적키, 표적키와 예측성인신장과의 차이, 혈청 IGF-1 및 IGFBP-3치를 비교하였다.
결 과 : 치료 시작시 두 군 간의 골연령, 표적키, 예측성인신장, 예측성인신장과 표적키의 차이는 없었으나 골연령과 역연령의 차이 및 역연령은 유의한 차이를 보였다. 혈청 IGF-1 및 IGFBP-3값의 차이는 없었고 평균 치료기간은 1.06±0.93년이었다. 치료 후의 골연령과 역연령의 차이는 전체적으로 감소하였으며 두 군간에도 유의한 차이를 보였다. 치료 후의 예측성인신장은 치료전과 비교했을 때 모두 증가하여 단기간의 치료에도 효과가 있었으며 두 군 모두 의미 있는 값을 가지나 특히 성장호르몬을 같이 사용한 2군에서 더욱 큰 차이를 보여 병합요법의 성장촉진효과를 알 수 있었다. 표적키와 예측성인신장의 차이는 전체적으로 치료전보다 의미 있는 감소를 보였으며 두 군을 비교했을때 역시 2군에서 더욱 의미 있게 감소하였다. 혈청 IGF-1과 IGFBP-3는 GnRHa 사용 후에 성장호르몬-IGF 축이 억제되어 1군에서 모두 감소하였으나 성장호르몬을 병합한 2군에서는 모두 증가하였고 이때 통계적인 의미는 없었다.
결 론 : 조기 사춘기로 인하여 역연령에 비해 골연령이 증가함으로써 성인신장에 나쁜 영향을 끼치는 경우에는 단기간의 GnRHa의 사용으로 사춘기의 빠른 진행을 억제하고 골성숙의 기간을 연장시킴으로써 예측성인신장을 증가시킬 수 있다. 또한 성장호르몬 병합요법으로 예측성인신장이 표적키에 도달하는데 있어 GnRHa 만으로 성장호르몬-IGF 축이 억제된 경우보다 성장촉진 효과를 나타낸다. 그러나 이는 단기간 사용 시의 치료효과이므로 최종성인신장의 비교를 위해서는 향후 장기적인 추적관찰이 필요하다.

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