Phenotypic Profiling of People With Subjective Tinnitus and Without a Clinical Hearing Loss

Abstract

Our objective was to study the characteristics of patients with subjective tinnitus and normal hearing and to investigate whether the features correlated to different shapes on audiograms. In this retrospective study, 313 patients with subjective tinnitus and clinically normal hearing were enrolled from the tinnitus outpatient department of the Eye and ENT Hospital of Fudan University. The following phenotypic variables were collected: age, dominant tinnitus pitch (TP), tinnitus loudness, tinnitus duration, tinnitus severity, sex, education, hearing thresholds, tinnitus position, and tinnitus condition. The dominant TPs of patients with normal hearing were mostly high-pitched, with a mean of 4866.8 ± 2579.6 Hz; thus, we speculated that the condition is related to high-frequency hearing threshold elevations. We further divided the patients into four subgroups based on the matched TP: (i) TP ≤ 500 Hz (n = 34), (ii) 500 Hz < TP ≤ 3,000 Hz (n = 15), (iii) 3,000 Hz < TP ≤ 8,000 Hz (n = 259), and (iv) TP > 8,000 Hz (n = 5). We studied the phenotypic profiling of different audiograms and found that the group with TP of ≤500 Hz had an average “inverted-U” shaped audiogram, and the group with TP between 500 and 3,000 Hz had a slowly ascending slope audiogram below 2,000 Hz, followed by a drastically descending slope audiogram ranging from 2,000 to 8,000 Hz; further, the high-frequency (3,000–8,000 Hz) and ultra-high-frequency (>8,000 Hz) groups had flat curves below 2,000 Hz and steeper slope audiograms over 2,000 Hz. Our findings confirmed a consistency ratio between the distributions of dominant TPs and the frequencies of maximum hearing thresholds in both ears. The dominant TP was positively correlated with the maximum hearing threshold elevation frequency (left ear: r = 0.277, p < 0.05; right ear: r = 0.367, p < 0.001). Hearing threshold elevations, especially in high frequency, might explain the appearance of dominant high-frequency TP in patients without clinically defined hearing loss. This is consistent with the causal role of high-frequency coding in the generation of tinnitus.

Mitochondrial Hearing Loss: Diagnosis and Management

“…Mitochondrial hearing loss presents with a diverse range of clinical manifestations, exhibiting considerable heterogeneity in terms of severity, age of onset, and progression of hearing impairment [1,2,[4][5][6]8]. The clinical features can vary among affected individuals and can include unilateral or bilateral hearing loss.…”

“…Some of the syndromes associated with mitochondrial hearing loss include Kearns-Sayre syndrome (KSS), Mitochondrial encephalopathy, lactic acidosis and stroke-like syndrome (MELAS), and maternally inherited diabetes and deafness (MIDD) syndrome. Each of these syndromes is associated with the loss of hearing along with multiple other systemic manifestations [2][3][4].…”

“…Mitochondrial disease is rare, affecting approximately 1 in 5000 individuals, but it contributes significantly to the overall burden of hearing loss [2,5]. Mitochondrial dysfunction is estimated to contribute to around 5% of non-syndromic post-lingual hearing loss and approximately 1% of pre-lingual cases [3,5].…”

“…These mutations are usually inherited from the mother due to the maternal inheritance pattern of mitochondrial DNA [1,4]. However, spontaneous mutations can also occur during mitochondrial DNA replication, leading to mitochondrial hearing loss [2,3,6].…”

“…The presence of noise has been shown to elevate the production of mitochondrial ROS, surpassing the cellular antioxidants' capacity and leading to oxidative stress. Consequently, cochlear hair cells may undergo apoptosis triggered by mitochondria, potentially resulting in their demise [1,2,5,6,8,9].…”