Studies in Patients with Congenital GnRH Deficiency

在这项研究中，我们正在对先天性促性腺激素释放激素(GnRH)分泌或反应不足的男性和女性进行表型/基因研究。孤立性促性腺激素释放激素缺乏是一种罕见的疾病，估计发病率为1/50,000。有青春期发育障碍和性腺激素低下症(低促黄体生成素、卵泡刺激素和雌二醇或睾酮)的患者，表明下丘脑或，较少的情况下，垂体腺异常。这种疾病被称为孤立性低促性腺激素减退症(IHH)。这些患者中约有50%缺乏嗅觉(Kallmann综合征，KS)，而另一半是正常的(NIHH)。对KS/nIHH患者的研究尤其有助于我们了解GnRH对正常生殖功能的要求，并导致在男性和女性中开发GnRH替代的生理学方案。虽然搏动性促性腺激素释放激素为有兴趣怀孕或对其怀孕潜力感兴趣的患者提供了治疗，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。我们目前活跃的方案侧重于进一步了解GnRH缺乏症的遗传基础，了解GnRH缺乏症患者的全部表型，以及了解这种疾病的基因/表型相关性。 这项研究是在马萨诸塞州综合医院和圣裘德医院的研究人员的支持下，在PI确定的患者中进行的，这是PI长期合作努力的一部分。

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.