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在MGH GCRC上，现在专注于详细描述因长期服用促性腺激素释放激素激动剂(GnRHa)而导致长期垂体-性腺抑制的中枢性早熟儿童的生长、最终身高和青春期结局。继续每隔6-12个月对服用GnRHa引起的长期垂体-性腺抑制的CPP儿童进行评估，这些儿童尚未完成线性生长和青春期发育。结果在CPP儿童的最初队列中，与治疗前的预测相比，完成他们的成长的儿童的成人身高在统计学上显着增加了4-6厘米。然而，最近的分析，包括了更多在年轻和青春期早期开始GnRHa治疗的患者，表明对最终身高的影响更大。在CA6年前登记的患者队列中，最终的HTS比治疗前预测的高8-10厘米。随着我们的最后一组年轻患者完成GnRHa治疗并在GnRHa后完成他们的生长发育，长期的性激素抑制对生长和最终身高的影响可能会贯穿我们患者群体的整个发育范围。研究人员继续监测GnRHa停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。正在进行后续治疗，以确定停止治疗数年的患者的生殖功能(包括生育能力)。最近，我们利用GnRHa给药可逆地抑制垂体-性腺功能的能力，进一步探讨了非类固醇FSH调节剂、抑制素A和B、卵泡抑素以及ob基因产物瘦素的生理学。

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.