Studies in Patients with Congenital GnRH Deficiency

在这项研究中，我们对先天性促性腺激素释放激素（GnRH）分泌或反应性缺乏的男性和女性进行表型/基因型研究。孤立性GnRH缺乏是一种罕见的疾病，估计发病率为1/50,000。患者表现为正常青春期发育失败和促性腺功能低下（LH、FSH和雌二醇或睾酮水平低），表明下丘脑或垂体异常（较少见）。这种疾病被称为孤立性促性腺功能减退症（IHH）。这些患者中大约有50%缺乏嗅觉（Kallmann综合征，KS），而另一半是正常的（nIHH）。对KS/nIHH患者的研究在帮助我们了解正常生殖功能对GnRH的需求方面提供了特别丰富的信息，并导致了男性和女性GnRH替代的生理方案的发展。虽然脉动性GnRH可以作为对怀孕感兴趣或有可能怀孕的患者的治疗方法，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。我们目前积极的方案集中在进一步了解GnRH缺乏症的遗传基础，了解GnRH缺乏症患者谱系的完整表型，以及了解这种疾病的基因型/表型相关性。

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.