Neely E Kirk, Silverman Lawrence A, Geffner Mitchell E, Danoff Theodore M, Gould Errol, Thornton Paul S
Pediatric Endocrinology and Diabetes, Stanford University, Stanford, California, USA.
Int J Pediatr Endocrinol. 2013 Dec 2;2013(1):20. doi: 10.1186/1687-9856-2013-20.
Gonadotropin-releasing hormone agonist (GnRHa)-stimulated luteinizing hormone (LH) is the standard hormonal assessment for both diagnosis and therapeutic monitoring of children with central precocious puberty (CPP). Use of unstimulated (random) LH levels may be helpful in diagnosis and has gained popularity in monitoring GnRHa therapy despite lack of validation against stimulated values. The objective of this investigation was to assess the suitability of random LH for monitoring pubertal suppression during GnRHa treatment.
Data from a multi-year, multicenter, open-label trial of annual histrelin implants for CPP was used for our analysis. Children meeting clinical and hormonal criteria for CPP, either naïve to GnRHa therapy or previously treated with another GnRHa for at least 6 months who were being treated at academic pediatric centers were included in the study. Subjects received a single 50-mg subcutaneous histrelin implant annually until final explant at an age determined at the discretion of each investigator. Monitoring visits for physical examination and GnRHa-stimulation testing were performed at regular intervals. The main outcome measure was pubertal suppression during treatment defined by peak LH < 4 mIU/mL after GnRHa stimulation.
During histrelin treatment, 36 children underwent a total of 308 monitoring GnRHa stimulation tests. Unstimulated and peak LH levels were positively correlated (r = 0.798), and both declined from the first to second year of treatment. Mean ± SD peak LH level during therapy was 0.62 ± 0.43 mIU/mL (range, 0.06-2.3), well below the normal prepubertal mean. Mean random LH was 0.35 ± 0.25 mIU/mL (range, 0.04-1.5), 10-fold higher than the normal prepubertal mean. The random LH levels were above the prepubertal upper threshold (<0.3 mIU/mL) in 48.4% of all tests and in 88.9% of subjects at some point during therapy.
In contrast with GnRHa-stimulated LH, unstimulated LH values frequently fail to demonstrate suppression to prepubertal values during GnRHa therapy for CPP, despite otherwise apparent pubertal suppression, and are thus unsuitable for therapeutic monitoring.
ClinicalTrial.gov NCT00779103.
促性腺激素释放激素激动剂（GnRHa）刺激后的促黄体生成素（LH）是中枢性性早熟（CPP）儿童诊断和治疗监测的标准激素评估指标。使用未刺激（随机）LH水平可能有助于诊断，并且在监测GnRHa治疗中越来越受欢迎，尽管缺乏与刺激值对比的验证。本研究的目的是评估随机LH在GnRHa治疗期间监测青春期抑制的适用性。
我们分析了一项针对CPP的多年、多中心、开放标签的醋酸组氨瑞林植入剂试验的数据。符合CPP临床和激素标准的儿童，无论是未接受过GnRHa治疗还是之前接受过另一种GnRHa治疗至少6个月且正在学术儿科中心接受治疗的儿童均纳入研究。受试者每年接受一次50mg皮下醋酸组氨瑞林植入，直至根据每位研究者的判断在确定的年龄进行最终取出。定期进行体格检查和GnRHa刺激试验的监测访视。主要结局指标是治疗期间的青春期抑制，定义为GnRHa刺激后LH峰值<4mIU/mL。
在醋酸组氨瑞林治疗期间，36名儿童共进行了308次监测GnRHa刺激试验。未刺激LH水平与LH峰值呈正相关（r=0.798），且两者在治疗的第一年到第二年均下降。治疗期间LH峰值的平均值±标准差为0.62±0.43mIU/mL（范围0.06-2.3），远低于青春期前正常平均值。随机LH的平均值为0.35±0.25mIU/mL（范围0.04-1.5），比青春期前正常平均值高10倍。在所有试验的48.4%以及88.9%的受试者治疗期间的某些时间点，随机LH水平高于青春期前上限阈值（<0.3mIU/mL）。
与GnRHa刺激后的LH不同，在CPP的GnRHa治疗期间，尽管青春期抑制在其他方面明显，但未刺激的LH值常常无法显示出抑制到青春期前水平，因此不适合用于治疗监测。
ClinicalTrial.gov NCT00779103。
