Unit and Chair of Endocrinology and Metabolism, Department of Biomedical, Metabolic and Neural Sciences, University of Modena and Reggio Emilia , Modena , Italy.
Front Endocrinol (Lausanne). 2013 Jun 7;4:70. doi: 10.3389/fendo.2013.00070. eCollection 2013.
Hypogonadotropic hypogonadism (HH) is a heterogeneous disease caused by mutations in several genes. Based on the presence of hyposmia/anosmia it is distinguished into Kallmann syndrome (KS) and isolated HH. The prevalence of other developmental anomalies is not well established.
We studied 36 patients with HH (31 males, 5 females, mean age 41.5), 9 with familial and 27 with sporadic HH (33 congenital, 3 adult-onset), by physical examination, smell test (BSIT Sensonics), audiometry, renal ultrasound, and magnetic resonance imaging of the olfactory structures.
Based on the smell test, patients were classified as normosmic (n = 21, 58.3%) and hypo/anosmic (n = 15, 41.6%). Hypoplasia/agenesis of olfactory bulbs was found in 40% of patients (10/25; 75% hypo/anosmic, 7.6% normosmic, p < 0.01, Fisher's test). Remarkably, olfactory structures were normal in two anosmic patients, while one normosmic patient presented a unilateral hypoplastic bulb. Fourteen of 33 patients (42.4%) presented neurosensorial hearing loss of various degrees (28.5% hypo/anosmic, 52.6% normosmic, p = NS). Renal ultrasound revealed 27.7% of cases with renal anomalies (26.6% hypo/anosmic, 28.5% normosmic, p = NS). At least one midline defect was found in 50% of the patients (53.3% hypo/anosmic, 47.6% normosmic, p = NS), including abnormal palate, dental anomalies, pectus excavatum, bimanual synkinesis, iris coloboma, and absent nasal cartilage. Anamnestically 4/31 patients reported cryptorchidism (25% hypo/anosmic, 5.2% normosmic, p = NS).
Hypo/anosmia is significantly related to anatomical anomalies of the olfactory bulbs/tracts but the prevalence of other developmental anomalies, especially midline defects and neurosensorial hearing loss, is high both in HH and KS and independent of the presence of anosmia/hyposmia. From the clinical standpoint KS and normosmic HH should be considered as the same complex, developmental disease.
低促性腺激素性性腺功能减退症（HH）是一种由几个基因的突变引起的异质性疾病。根据嗅觉缺失/减退的存在，它分为卡尔曼综合征（KS）和孤立性 HH。其他发育异常的患病率尚不清楚。
我们研究了 36 名 HH 患者（31 名男性，5 名女性，平均年龄 41.5 岁），其中 9 名有家族史，27 名散发性 HH（33 名先天性，3 名成年发病），通过体格检查、嗅觉测试（BSIT Sensonics）、听力测试、肾脏超声和嗅觉结构的磁共振成像进行研究。
根据嗅觉测试，患者分为正常嗅觉（n=21，58.3%）和嗅觉减退/缺失（n=15，41.6%）。40%的患者嗅球发育不良/发育不全（n=10/25；75%嗅觉减退/缺失，7.6%嗅觉正常，p<0.01，Fisher 检验）。值得注意的是，两名嗅觉缺失的患者嗅觉结构正常，而一名嗅觉正常的患者则表现为单侧嗅球发育不全。33 名患者中有 14 名（42.4%）有不同程度的感觉神经性听力损失（28.5%嗅觉减退/缺失，52.6%嗅觉正常，p=NS）。肾脏超声显示 27.7%的患者有肾脏异常（26.6%嗅觉减退/缺失，28.5%嗅觉正常，p=NS）。50%的患者至少有一个中线缺陷（53.3%嗅觉减退/缺失，47.6%嗅觉正常，p=NS），包括异常的腭、牙齿异常、漏斗胸、双手协同运动、虹膜裂、鼻软骨缺失。4/31 名患者有隐睾症病史（25%嗅觉减退/缺失，5.2%嗅觉正常，p=NS）。
嗅觉减退/缺失与嗅球/嗅束的解剖异常显著相关，但 HH 和 KS 中其他发育异常（尤其是中线缺陷和感觉神经性听力损失）的患病率很高，且与嗅觉缺失/减退无关。从临床角度来看，KS 和正常嗅觉 HH 应被视为同一复杂的发育性疾病。
