title: Prevalence of olfactory and other developmental anomalies in patients with central hypogonadotropic hypogonadism.
abstract: BACKGROUND
  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.
  
  
  METHODS
  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.
  
  
  RESULTS
  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).
  
  
  CONCLUSIONS
  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.
authors.affiliation: Unit and Chair of Endocrinology and Metabolism, Department of Biomedical, Metabolic and Neural Sciences, University of Modena and Reggio Emilia , Modena , Italy.
authors.forename: Elisa
authors.initials: E
authors.lastname: Della Valle
authors.forename: Silvia
authors.initials: S
authors.lastname: Vezzani
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Rochira
authors.forename: Antonio Raffaele Michele
authors.initials: AR
authors.lastname: Granata
authors.forename: Bruno
authors.initials: B
authors.lastname: Madeo
authors.forename: Elisabetta
authors.initials: E
authors.lastname: Genovese
authors.forename: Elisa
authors.initials: E
authors.lastname: Pignatti
authors.forename: Marco
authors.initials: M
authors.lastname: Marino
authors.forename: Cesare
authors.initials: C
authors.lastname: Carani
authors.forename: Manuela
authors.initials: M
authors.lastname: Simoni
keywords: Kallmann syndrome; central hypogonadotropic hypogonadism; developmental anomalies; hypothalamic-pituitary-gonadal axis; midline defects; neurosensorial hearing loss; smell test