성조숙증 여아에서 성선자극호르몬방출호르몬유도체 단독 치료와 성장호르몬 병합 치료가 예측성인신장에 미치는 영향
The Effect of Gonadotropin Releasing Hormone Agonist and Growth Hormone on Predicted Adult Height in Girls with Precocious Puberty
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목 적 : 예측성인키가 작을 것으로 예상되는 성조숙증 여아에서 GnRH agonist 단독 치료 또는 성장 호르몬과의 병합 치료가 사춘기를 억제하고 최종 성인키에 기여하는지에 대한 여부와 이에 영향을 미치는 인자들에 대해 알아보고자 하였다. 방 법 : 2003년 3월부터 2006년 11월까지 만 5세부터 만 8세까지 Tanner stage II 이상의 사춘기 발달을 주소로 내원한 여아들 중 골연령이 역연령에 비해 1년 이상 진행되었고 예측성인키(predicted adult height, PAH)가 표적키에 비해 현저히 작으며 GnRH 자극 검사 양성을 보여 6개월 이상 GnRH agonist를 투여 받은 여아 41명을 대상으로 하였다. 이들 중 17명은 성장호르몬을 병합투여 하였다. 치료 시작 전 역연령, 키, 골연령 및 성장호르몬 병합 투여 등이 치료 후 예측성인키에 미치는 영향에 대해 independent t- test, paired t-test, ANOVA, multiple linear regression의 통계를 이용해 분석하였다. 결 과 : 전체 대상아 41명을 GnRH agonist만 투여 받은 24명과 성장호르몬을 병합투여 받은 17명의 두 군으로 나누었다. 이 두 군의 치료 시작 전 역연령, 골연령, 키, 몸무게, 체질량지수, Tanner stage는 통계학적으로 유의한 차이가 없었으나 성장호르몬을 병합 투여한 군에서 표적키가 155.3±3.01 cm로 GnRH agonist 단독 투여 군의 표적키 158.3±4.46 cm보다 작았다(P=0.037). 성장호르몬을 병합 투여한 군의 경우 성장 속도가 6개월 후부터 1년까지 5.8±0.70 cm/year(P=0.001)로 GnRH agonist 단독 투여한 군의 4.0±0.82 cm/year보다 증가하였고(P=0.001) 두 군 모두에서 치료 기간동안 골연령은 잘 억제되고 있었다. 전체 대상아 41명에서 치료 전 예측성인키는 153.8±6.90 cm/year로 표적키 157.1±4.17 cm/year보다 작았으나(P=0.007) 치료 후 예측성인키는 158.8±5.82 cm/year로 표적키와 차이를 보이지 않았고 치료 후 예측 성인키와 치료 전 예측성인키의 차이를 치료 효과로 보았을 때 치료 전 예측성인키가 작을수록(P=0.015) 그리고 치료 기간이 길수록(P=0.009) 통계적으로 의미 있었고 예측성인키 증가에 기여하였다. 결 론 : 성조숙증 여아에서 GnRH agonist 치료는 골연령을 억제하여 예측성인키 증가에 효과가 있으며 그 효과는 치료 시작 시 예측성인키가 작고, 치료 기간이 길수록 더 컸다. 그리고 성장 호르몬을 병합 투여할 경우, GnRH agonist를 단독 투여할 경우보다 처음 1년간 성장 속도가 의미 있게 증가하고 예측성인키 획득이 크므로 예측성인키가 작은 성조숙증 여아에서는 GnRH agonist와 성장호르몬을 병합 투여하는 것이 더 좋을 것으로 사료된다.
Abstract
Purpose : Gonadotropin releasing hormone agonist (GnRH agonist) and growth hormone (GH) treatment is widely used in precocious puberty to delay rapid pubertal growth. We studied the effect of these agents on the predicted adult height in girls with precocious puberty. Methods : 41 girls were selected who had precocious sexual development, with onset from 5 to 8 years of age. They were divided into two groups. Twenty four girls treated only with GnRH agonist were compared with 17 girls treated with GnRH agonist and GH. We analyzed chronologic age (CA), bone age (BA) and predicted adult height (PAH) during and after treatment. Results : Before treatment, there were no differences for CA, BA, body mass index (BMI), PAH and Tanner stage between two groups. After treatment, the PAH [153.7±6.85 cm (-1.31±1.25 SDS) vs 158.8±5.82 cm (-0.30±1.24 SDS)] for both age groups were significantly increased. The difference between initial PAH and follow up PAH was significantly increased when the initial PAH was low (P=0.015), and the duration of treatment was long (P=0.009). Conclusion : In girls with precocious puberty, GnRH agonist delayed bone maturation and increased PAH. PAH increased more when GnRH agonist and GH treatment was used as opposed to GnRH agonist treatment alone. GH combination therapy should be considered if the initial PAH was very low.
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