Characteristics of a nationwide cohort of patients presenting with isolated hypogonadotropic hypogonadism (IHH)
Characteristics of a nationwide cohort of patients presenting with isolated hypogonadotropic hypogonadism (IHH)
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DOI：
10.1530/eje-17-0065
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发表时间：
2018-01-01
影响因子：
5.8
通讯作者：
Persani, Luca
中科院分区：
文献类型：
--
作者：
Bonomi, Marco;Vezzoli, Valeria;Persani, Luca
目的：孤立性促性腺功能减退症（IHH）是一种少见的青春期发育迟缓、嗅觉正常（正常-IHH， nIHH）或嗅觉缺陷（Kallmann综合征，KS）的疾病。其他生殖和非生殖异常也可能存在，但关于其频率的资料很少，特别是根据出现的年龄。设计：观察性队列研究于2008年1月至2016年6月在全国学术或综合医院网络中进行。方法：我们对503例IHH患者进行了详细的表型分析：(1)表现为性腺功能减退，性类固醇激素水平低，促性腺激素水平低/正常；(2)无扩张性下丘脑/垂体病变或多种垂体激素缺陷。按IHH发病（PPO，青春期前发病或AO，成年发病）和嗅觉功能分为队列：PPO- nihh (n = 275), KS (n = 184), AO- nihh （n = 36）和AO- doihh （AO-IHH伴有嗅觉缺陷，n = 8）。结果：90%的患者归为PPO， 10%归为AO。在AO-IHH中还发现了典型的中线和嗅觉缺陷，双手联觉和青春期延迟熟悉。Kallmann综合征（KS）患者的平均诊断年龄明显更早且更频繁地与先天性性腺功能减退相关。联合运动、肾脏和男性生殖道异常在KS中丰富。超重/肥胖与AO-IHH显著相关，而非PPO-IHH。结论：KS患者比nIHH患者更容易出现严重和复杂的表型。在AO-IHH患者中存在典型的性腺外缺陷和对PPO-IHH的熟悉表明具有不同临床表达的共同易感性。总的来说，这些发现提高了对IHH的理解，并可能对患者及其家属的管理产生积极影响。
Objective: Isolated hypogonadotropic hypogonadism (IHH) is a rare disorder with pubertal delay, normal (normoosmic-IHH, nIHH) or defective sense of smell (Kallmann syndrome, KS). Other reproductive and nonreproductive anomalies might be present although information on their frequency are scanty, particularly according to the age of presentation.Design: Observational cohort study carried out between January 2008 and June 2016 within a national network of academic or general hospitals.Methods: We performed a detailed phenotyping of 503 IHH patients with: (1) manifestations of hypogonadism with low sex steroid hormone and low/normal gonadotropins; (2) absence of expansive hypothalamic/pituitary lesions or multiple pituitary hormone defects. Cohort was divided on IHH onset (PPO, pre-pubertal onset or AO, adult onset) and olfactory function: PPO-nIHH (n = 275), KS (n = 184), AO-nIHH (n = 36) and AO-doIHH (AO-IHH with defective olfaction, n = 8).Results: 90% of patients were classified as PPO and 10% as AO. Typical midline and olfactory defects, bimanual synkinesis and familiarity for pubertal delay were also found among the AO-IHH. Mean age at diagnosis was significantly earlier and more frequently associated with congenital hypogonadism stigmata in patients with Kallmann's syndrome (KS). Synkinesis, renal and male genital tract anomalies were enriched in KS. Overweight/obesity are significantly associated with AO-IHH rather than PPO-IHH.Conclusions: Patients with KS are more prone to develop a severe and complex phenotype than nIHH. The presence of typical extra-gonadal defects and familiarity for PPO-IHH among the AO-IHH patients indicates a common predisposition with variable clinical expression. Overall, these findings improve the understanding of IHH and may have a positive impact on the management of patients and their families.