진성 성조숙증 여아의 치료에서 GnRH agonist 투여 후 1회 측정한 LH 농도를 이용한 모니터링의 유용성
Efficacy of a Single Luteinizing Hormone Measurement after GnRH Agonist Administration for Therapeutic Monitoring of Girls with Central Precocious Puberty
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목적: 진성 성조숙증 환자에서 성선자극호르몬 방출호르몬 효능 약제 GnRH agonist 치료 중 사춘기 억제 상태를 평가하는 것은 중요하나 표준 검사로 알려진 GnRH 자극 검사는 비용과 시간이 많이 들고 환자에게 불편하다는 단점이 있다. 본 연구에서는 GnRH agonist 투여 2시간 뒤에 1회 측정한 황체형성호르몬 농도를 통해 사춘기 억제 여부를 평가하고자 하였다. 방법: 8세 이전에 유방 발달을 보인 여아에서 GnRH 자극 검사를 통해 peak LH 농도가 5 IU/L 이상 증가하고 골역령이 역연령보다 증가되어 있으며 만 9세 이전에 GnRH agonist 치료를 시작한 148명의 환자를 대상으로 하였다. 치료시작 후 6개월 마다 GnRH agonist 투여 후 2시간 뒤에 LH, FSH를 면역방사계수법으로, estradiol은 방사면역법으로 측정하였고 골연령과 신장을 측정하였다. 사춘기가 억제된 경우는 성 성숙도가 진행되지 않고, 6개월간의 골연령/역연령 비의 변화가 1 이하이며, 신장표준편차점수의 차이가 6개월간 0.25 이하인 경우를 모두 만족할 때로 정하였다. 치료 기간 동안 임상적으로 사춘기가 억제된 군과 억제되지 않은 군에서 GnRH agonist 투여 후 2시간 째 측정한 LH 농도를 ROC curve를 통해 적절성을 평가하였다. 결과: 증상이 발현된 평균 나이는 7.2±0.93세였고 치료 시작시 평균 연령과 골연령은 각각 8.2±0.94, 10.1±1.1세였다. 기질적 원인을 가지고 있던 환아는 8명으로 2명은 과오종이었고, 뇌수종과 뇌척수염이 각각 2명, 성상세포종과라트케열 낭종이 각각 1명이었다. 그리고 질환과 무관하게 우연히 발견된 정맥 혈관종이 1명 있었다. 치료 전 GnRH 자극 검사를 시행하였을 때 LH 농도의 기저치, 최고치는 1.56±1.1, 18.2±12.1 IU/L 였다. 39명에서 사춘기가 충분히 억제되지 않았다. ROC 곡선에서 cut-off value는 ＜2.5 IU/L이었고 민감도와 특이도는 각각 82.6%, 51.3%였으며AUC 값은 0.674이었다. 결론: 진성 성조숙증 환자에서 치료 모니터링을 위해 GnRH agonist 투여 후 2시간째 측정한 LH 농도의 cut-off value는 2.5 IU/L 미만이 유용할 것으로 보인다. 표준적인 GnRH 자극 검사와 다른 방법으로 간단하고 편리하며 저렴한 비용으로 진성 성조숙증 환자의 치료 경과를 모니터링 할 수 있겠다. 다만 AUC가 낮아, 향후 민감도가 높은immunochemiluminometric assay로 측정한 LH를 모니터링하여 결과를 비교해 보는 것이 필요하겠다.
Abstract
Purpose: The effectiveness of gonadotropin releasing hormone (GnRH) agonist therapy in central precocious puberty (CPP) depends on the suppression of luteinizing hormone (LH) secretion. The purpose of this study was to determine the utility of a single luteinizing hormone measurement after GnRH agonist injection for the therapeutic monitoring of CPP. Methods: The study included 148 females with CPP who had been treated with GnRH agonist. During the therapy, suppression of their pubertal development was assessed based on their height standard deviation score (SDS), bone age, and pubertal stage. Every six months, their serum LH and follicular stimulating hormone (FSH) levels were measured using immunoradiometric assays. Their estradiol levels were also assayed using radioimmunoassay two hours following GnRH agonist administration. Results: The means of the onset age, bone age, and chronological age were 7.2±0.93,10.1 ± 1.1, and 8.2 ± 0.94 years, respectively. Eight patients had pathologic intracranial lesions including harmatoma, hydrocephalus, meningitis, astrocytoma, and Rathke’s cleft cyst. The basal and peak LH levels were 1.56 ± 1.1 and 18.2 ± 12.1 IU/L, respectively. In 39 females with CPP, pubertal development was not sufficiently suppressed even after one year of therapy. The receiver operating characteristic (ROC) curve showed a cutoff value of LH for pubertal suppression of less than 2.5 IU/L. The area under the curve (AUC) was 0.674. Conclusion: The cutoff value of 2.5 IU/L for a LH measurement, taken two hours following subcutaneous GnRH agonist injection, is adequate for therapeutic monitoring of females with CPP. This method is both convenient and cost effective.
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