title: Endolymphatic sac tumors. A source of morbid hearing loss in von Hippel-Lindau disease.
abstract: OBJECTIVE
  Isolated reports suggest a possible association of endolymphatic sac tumors (ELSTs), which are extremely rare in the general population, with von Hippel-Lindau disease (VHL). To determine if hearing loss and ELSTs are a component of VHL, we examined prevalence, clinical presentation, and natural history of hearing loss and ELSTs in VHL.
  
  
  METHODS
  Brain magnetic resonance images (MRIs) from 374 patients screened for VHL were reviewed for evidence of ELSTs. The VHL patients with MRI evidence suggestive of ELSTs or a history of hearing loss, tinnitus, or vertigo underwent additional radiologic and audiologic evaluations. To further assess prevalence of hearing loss and ELST in VHL, the next 66 patients screened in the VHL clinic (49 with proven VHL, 17 at risk for VHL) received MRI and audiologic assessment.
  
  
  METHODS
  Referral center.
  
  
  METHODS
  Study subjects comprised 374 persons screened for VHL, 66 consecutive patients with VHL or at risk for VHL, 4 patients with 6 ELSTs, and 13 previously reported patients with VHL and invasive tumors of the temporal bone.
  
  
  METHODS
  Magnetic resonance image and computed tomographic (CT) scan of the posterior fossa and audiologic assessment.
  
  
  METHODS
  Any ELST visible on MRI or CT and hearing loss compatible with ELST.
  
  
  RESULTS
  Magnetic resonance imaging revealed evidence of 15 ELSTs in 13 (11%) of 121 patients with VHL, but in none of the 253 patients without evidence of VHL (P<.001). Clinical findings in these 13 patients included hearing loss (13), tinnitus (12), vertigo (8), and facial paresis (1). Mean age at onset of hearing loss was 22 years (range, 12-50 years). Hearing for pure tones was abnormal in all affected ears and in 6 of the 11 additional, allegedly unaffected ears. In 8 patients (62%), hearing loss was the first manifestation of VHL. Presence or absence of hearing loss was associated with duration of symptoms (P<.002) and with tumor size (P<.01). Further, 43 (65%) of the 66 patients from the VHL clinic had pure tone threshold abnormalities, abnormalities that occurred bilaterally in 23 (54%) of the 43 affected subjects; however, evidence is lacking for a definitive association with ELST (3 [6%] of 49 patients with proven VHL had ELST evident on MRI).
  
  
  CONCLUSIONS
  Hearing loss and ELSTs are frequently associated with VHL syndrome and should be considered when screening individuals at risk for VHL and when monitoring patients with an established diagnosis of VHL. Many patients with VHL have hearing loss without radiographic evidence of an ELST. Whether it is caused by an ELST that is too small to be detected by MRI or is produced by some other etiology is still unknown. Audiologic evaluation and MRI should allow early detection and enhance management of hearing loss in these patients.
authors.affiliation: Surgical Neurology Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD 20892-1414, USA.
authors.forename: T J
authors.initials: TJ
authors.lastname: Manski
authors.forename: D K
authors.initials: DK
authors.lastname: Heffner
authors.forename: G M
authors.initials: GM
authors.lastname: Glenn
authors.forename: N J
authors.initials: NJ
authors.lastname: Patronas
authors.forename: A T
authors.initials: AT
authors.lastname: Pikus
authors.forename: D
authors.initials: D
authors.lastname: Katz
authors.forename: R
authors.initials: R
authors.lastname: Lebovics
authors.forename: K
authors.initials: K
authors.lastname: Sledjeski
authors.forename: P L
authors.initials: PL
authors.lastname: Choyke
authors.forename: B
authors.initials: B
authors.lastname: Zbar
authors.forename: W M
authors.initials: WM
authors.lastname: Linehan
authors.forename: E H
authors.initials: EH
authors.lastname: Oldfield
mesh_terms: D017668:Age of Onset; D001299:Audiometry; D001921:Brain / Q000473:pathology; D003388:Cranial Fossa, Posterior / Q000000981:diagnostic imaging / Q000473:pathology; D004428:Ear Neoplasms / Q000150:complications* / Q000175:diagnosis; D004712:Endolymphatic Sac / Q000000981:diagnostic imaging / Q000473:pathology; D016147:Genes, Tumor Suppressor; D006311:Hearing Disorders / Q000150:complications*; D034381:Hearing Loss / Q000150:complications; D006801:Humans; D008025:Ligases; D008279:Magnetic Resonance Imaging; D009154:Mutation; D010579:Petrous Bone / Q000000981:diagnostic imaging / Q000473:pathology; D011506:Proteins / Q000235:genetics; D012189:Retrospective Studies; D014057:Tomography, X-Ray Computed; D025521:Tumor Suppressor Proteins; D044767:Ubiquitin-Protein Ligases; D051794:Von Hippel-Lindau Tumor Suppressor Protein; D006623:von Hippel-Lindau Disease / Q000150:complications* / Q000175:diagnosis / Q000235:genetics
chemical_list: D011506:Proteins; D025521:Tumor Suppressor Proteins; D044767:Ubiquitin-Protein Ligases; D051794:Von Hippel-Lindau Tumor Suppressor Protein; D008025:Ligases; C497446:VHL protein, human