Studies in Patients with Congenital GnRH Deficiency

在这项研究中，我们正在进行表型/基因型研究的男性和女性先天性缺陷的分泌或反应性促性腺激素释放激素（GnRH）。 孤立性GnRH缺乏症是一种罕见的疾病，估计发病率为1/50，000。患者表现为正常青春期发育失败和低促性腺激素性性腺功能减退症（LH、FSH和雌二醇或睾酮水平低），提示下丘脑或垂体异常（不太常见）。这种疾病被称为孤立性低促性腺激素性性腺功能减退症（IHH）。这些患者中约50%缺乏嗅觉（卡尔曼综合征，KS），而另一半嗅觉正常（nIHH）。在KS/nIHH患者中的研究在帮助我们了解正常生殖功能的GnRH需求方面提供了特别丰富的信息，并导致了男性和女性GnRH替代生理方案的发展。虽然脉冲式GnRH可用于治疗有兴趣怀孕或有可能怀孕的患者，但这些患者提供了一个临床模型，使我们能够解决生殖生理学中的关键问题。我们目前积极的协议集中在进一步了解GnRH缺乏症的遗传基础，了解与GnRH缺乏症的患者谱的完整表型，并了解这种疾病的基因型/表型的相关性。 作为PI长期合作努力的一部分，本研究在马萨诸塞州总医院和St Jude's医院研究者的支持下，在PI确定的患者中进行。

In this study we are performing phenotype/genotype studies in males and women with congenital deficiency in the secretion or responsiveness to gonadotropin releasing hormone (GnRH). Isolated GnRH deficiency is a rare disorder, with an estimated incidence of 1/50,000. Patients present with failure of normal pubertal development and hypogonadotropic hypogonadism (low LH, FSH and estradiol or testosterone), indicative of a hypothalamic or, less frequently, pituitary abnormality. The disorder is referred to as isolated hypogonadotropic hypogonadism (IHH). Approximately 50% of these patients lack a sense of smell (Kallmann Syndrome, KS) while the other half are normosmic (nIHH). Studies in KS/nIHH patients have been particularly informative in helping us understand the GnRH requirements for normal reproductive function and have led to development of a physiologic regimen of GnRH replacement in men and women. While pulsatile GnRH serves as treatment for patients interested in conceiving or in their potential to conceive, these patients have provided a clinical model that allows us to address key questions in reproductive physiology. Our currently active protocols focus on further understanding the genetic underpinnings of GnRH deficiency, understanding the full phenotype of the spectrum of patients who present with GnRH deficiency and understanding the genotype/phenotype correlations in this disorder. This study is being conducted in patients identified by the PI with the support of investigators at Massachusetts General Hospital and St Jude's Hospital as is part of the PIs long-term collaborative efforts.