LRF ANALOG TO DELAY PUBERTY IN PRECOCIOUS PUBERTY, GH DEFICIENCY, SHORT STATURE

该项目自20世纪80年代初以来一直活跃于MGH GCRC，现在专注于中枢性性早熟（CPP）儿童的生长，最终身高和青春期结局的详细表征，这些儿童经历了长期给予GnRH激动剂（GnRHa）诱导的长期垂体-性腺抑制。 在接受GnRHa给药诱导的长期垂体-性腺抑制且尚未完成线性生长和青春期发育的CPP儿童中，继续每隔6-12个月进行一次评价。与治疗前的预测相比，完成生长的CPP儿童初始队列的结果定义了4-6厘米的成人身高统计学显着增加。 然而，最近的分析纳入了更多在年轻时和青春期早期开始GnRHa治疗的患者，表明对最终身高的影响更大。 在CA 6年前入组的患者队列中，最终HT超过治疗前预测值8-10 cm。 随着我们最后一组年轻患者完成GnRHa治疗并在GnRHa后完成生长，可以在我们患者人群的整个发育谱中观察长期性腺性类固醇抑制对生长和最终身高的影响。研究者继续监测停止GnRHa给药后青春期垂体功能的恢复以及成熟生殖内分泌功能的最终发展。 正在进行随访，以表征已停止治疗数年的患者的生殖功能（包括生育力）。 最近，我们已经利用GnRHa给药可逆抑制垂体-性腺功能的能力，进一步探索非甾体FSH调节剂、卵泡抑素A和B以及瘦素（ob基因的产物）的生理学。

This project, which has been active on the MGH GCRC since the early 1980's, now focuses on detailed characterization of the growth, final height, and pubertal outcomes of children with central precocious puberty (CPP) who have undergone long-term pituitary-gonadal suppression induced by chronic administration of a GnRH agonist (GnRHa). Evaluations continue to be performed at 6-12 month intervals in children with CPP who have undergone long-term pituitary-gonadal suppression induced by GnRHa administration and who have not yet completed their linear growth and pubertal development. Results in the initial cohort of children with CPP who completed their growth defined a statistically significant increase in adult stature of 4-6 cm compared to pretherapy predictions. However, recent analyses which have included more patients who initiated GnRHa treatment at younger ages and earlier stages of puberty demonstrate a more substantial effect on final height. In the cohort of patients enrolled before CA 6 years, final HTs exceed pretherapy predictions by 8-10 cm. As our final group of young patients complete their therapy with GnRHa and complete their growth post-GnRHa, the impact of long-term gonadal sex steroid suppression on growth and final height may be viewed across the full developmental spectrum of our patient population. The investigators continue to monitor the return of pubertal pituitary function following the discontinuation of GnRHa administration and the eventual development of mature reproductive endocrine function. Follow-up is underway to characterize reproductive function (including fertility) in patients in whom therapy has been discontinued for several years. Most recently, we have utilized the ability of GnRHa administration to reversibly suppress pituitary-gonadal function to probe further the physiology of the non-steroidal FSH regulators, inhibin A & B and follistatin, and leptin, the product of the ob gene.