Tumor Size Not Related to Hearing Loss in von Hippel-Lindau Disease

BETHESDA, Md., July 3 -- Even small, asymptomatic, endolymphatic sac tumors associated with von Hippel-Lindau disease may require surgery to prevent hearing loss, NIH researchers reported.
In a study to determine the mechanisms of sensorineural hearing loss and optimal treatment timing in patients with the condition, John A. Butman, M.D., Ph.D., of the NIH Clinical Center, and colleagues, found that hearing loss could occur suddenly from intralabyrinthine hemorrhage, and was unrelated to tumor size.
"Since significant audiovestibular dysfunction, including deafness, can occur suddenly in a manner that is not related to tumor size, early surgical intervention may be warranted," the investigators wrote in the July 4 issue of the Journal of the American Medical Association.
Von Hippel-Lindau disease is a rare (1 in 39,000 individuals), autosomal dominant, multi-system disorder characterized by angiomatosis.
Patients with the disease may sporadically develop endolymphatic sac tumors, benign but locally aggressive and highly vascular lesions that cause sudden, irreversible hearing loss.
The authors conducted a prospective, serial study of 35 patients with von Hippel-Lindau disease and endolymphatic sac tumors who were seen at the National Institutes of Health from May 1990 through December 2006.
The primary study endpoints were clinical findings and audiologic data, and their correlation with serial MRI and CT studies, with the goal of identifying the underlying mechanisms leading to audiovestibular dysfunction.
Based on the relationship between the imaging and clinical findings in these patients, three distinct mechanisms were found to account for the audiovestibular morbidity associated with the tumors. These include direct invasion of the otic capsule by the tumor, intralabyrinthine hemorrhage, and endolymphatic hydrops.
Among the 35 patients (three of whom had bilateral tumors), the authors found that in seven ears the tumors invaded the otic capsule, and that the tumors were significantly more likely to be large (P=0.01). These tumors caused sensorineural hearing loss in all patients in whom they occurred.
Although there was no evidence of invasion of the otic capsule in the remaining 31 ears (suggesting that they could be managed conservatively according to current clinical practice), 27 of the ears still developed sensorineural hearing loss. The loss occurred suddenly in 14 of the 27 ears, and gradually in 13. The remaining four ears retained normal hearing.
The authors also found that 11 of the 14 ears with sudden hearing loss but no otic invasion, had sustained intralabyrinthine hemorrhage (P<0.001). In contrast, none of the 13 ears with gradual hearing loss, nor the four ears with no hearing loss, had any evidence of hemorrhage.
They also found that tumor size was not associated with either sensorineural hearing loss (P=0.23) or with vestibulopathy (P=0.83).
"Endolymphatic sac tumor-associated sensorineural hearing loss and vestibulopathy may occur suddenly due to tumor-associated intralabyrinthine hemorrhage, or insidiously, consistent with endolymphatic hydrops," the authors wrote. "Both of these pathophysiologic mechanisms occur with small tumors that are not associated with otic capsule invasion."
Although they did not study the effects of surgery to prevent hearing loss in patients with von Hippel-Lindau disease, the authors noted that, in several small studies, completed resection of endolymphatic sac tumors has been shown to be curative, preserving hearing with minimal morbidity.
"To intervene early, prompt diagnosis based on clinical and imaging findings is necessary," they wrote. "Thus, serial clinical evaluations and high-resolution MRI and CT imaging to detect small endolymphatic sac tumors or intralabyrinthine hemorrhage are warranted in patients with vestibular hearing loss."
The study was supported by the National Institutes of Health. The authors had no conflicts of interest to report. Additional source: Journal of the American Medical AssociationSource reference: Butman JA et al. "Mechanisms of Morbid Hearing Loss Associated With Tumors of the Endolymphatic Sac in von Hippel-Lindau Disease." JAMA. 2007;298(1):41-48.