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 Table of Contents  
ORIGINAL ARTICLE
Year : 2017  |  Volume : 23  |  Issue : 4  |  Page : 226-229

Hyperuricemia effects auditory functions


1 Department of Otolaryngology Head and Neck Surgery, Dr. RP Government Medical College, Tanda, Kangra, India
2 Department of Otolaryngology Head and Neck Surgery, Indira Gandhi Medical College, Shimla, Himachal Pradesh, India
3 Department of Medicine, Dr. RP Government Medical College, Tanda, Kangra, India

Date of Web Publication2-May-2018

Correspondence Address:
Dr. Jagdeep S Thakur
Department of Otolaryngology Head and Neck Surgery, Indira Gandhi Medical College, Shimla - 171 001, Himachal Pradesh
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/indianjotol.INDIANJOTOL_18_17

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  Abstract 


Aim: The aim of this article is to study the effect of hyperuricemia on auditory functions. Materials and Methods: This was an academic institution (Indira Gandhi Medical College, Shimla, HP, India)-based, prospective, observational case–control study with 25 hyperuricemic individuals. Individuals with any confounding factor were excluded from the study. Cochlear functions were evaluated using pure tone audiometry, transient evoked otoacoustic emission (TEOAE), and distortion product otoacoustic emission (DPOAE). Results: This study found reduced responses at higher frequencies on DPOAE and TEOAE in the case group. On TEOAE, statistically significant difference was observed in the signal-noise ratio at 4 and 3 KHz with P < 0.001. Signal-noise ratio of DPOAE was also found statistically significant at 5 and 6 KHz. Conclusions: This study found association of asymptomatic hyperuricemia and hearing loss, especially at high frequencies. In our opinion, hyperuricemia causes cochlear damage through crystal formation and minor vessel atherosclerosis.

Keywords: Hearing loss, hyperuricemia, otoacoustic emission, outer hair cell


How to cite this article:
Saini A, Thakur JS, Saini G, Sharma DR, Mohindroo NK. Hyperuricemia effects auditory functions. Indian J Otol 2017;23:226-9

How to cite this URL:
Saini A, Thakur JS, Saini G, Sharma DR, Mohindroo NK. Hyperuricemia effects auditory functions. Indian J Otol [serial online] 2017 [cited 2018 Aug 15];23:226-9. Available from: http://www.indianjotol.org/text.asp?2017/23/4/226/231643




  Introduction Top


Various metabolic disorders have been associated with hearing loss due to their direct or indirect effect on the cochlea. Cochlea has complex and terminal blood supply, and subtle changes in vascular supply affect stria vascularis and outer hair cell.[1] Recently, hyperuricemia has been implicated in cardiovascular diseases by causing vascular calcification and hypertension,[2],[3],[4] and hence, hyperuricemia can lead to indirect cochlear injury. However, a systemic review has found weak association between hyperuricemia and cardiovascular diseases.[5] It is therefore, we performed a prospective, observational study to find association of hyperuricemia and hearing loss. We assessed cochlear functions by evoked otoacoustic emission (OAE) since it has unmatched screening and monitoring tool in hearing impairment related to aging,[6] noise exposure,[7] ototoxic drug,[8] and metabolic disorders such as atherosclerosis, hypercholesterolemia/dyslipidemia, and hyperglycemia.[9],[10],[11]


  Materials and Methods Top


This was a case–control, prospective, observational study conducted in an academic institute (Indira Gandhi Medical College, Shimla, HP, India) after informed consent and ethical board approval. The study sample consisted of 25 hyperuricemic naïve individuals and equal number of age- and sex-matched normal individuals as controls in the age group of 20–51 years with 15 males and 10 females in each group. Case group had mean age of 36.16 ± 9.66 years while control group had mean age of 35.8 ± 9.46 years. Individuals with a history or laboratory evidence of ear discharge, smoking, alcoholism, noise exposure, ototoxic drugs, renal insufficiency, diabetes mellitus, hypertension, hypercholesterolemia/dyslipidemia, or any other disease known to cause hearing loss and abnormal ear findings on clinical examination were excluded from the study.

Case group had mean serum uric acid level of 9.42 ± 1.85 mg% while control group had 3.41 ± 0.83 mg%. After clinical and biochemical examination, all participants were subjected to pure tone audiometric and distortion product OAEs and transient evoked OAEs (DPOAEs and TEOAEs) testing as per the International Standard with Interacoustics AC 40 Clinical Audiometer (Interacoustics A/S, Assens, Denmark) and GSI audioscreener+ (VIASYS NeuroCare, Madison, USA), respectively, in a fully sound attenuated room situated in the department. Observations were recorded and subjected to statistical analysis. Intergroup comparison was performed for audiometric observations. As duration of hyperuricemia and levels of uric acid may have effect on hearing, cases were divided further into subgroups, i.e., one set of subgroup on hyperuricemia ≤3 years and >3 years, and other two subgroups with serum uric acid ≤9 mg% and >9 mg%.


  Results Top


Pure tone audiometry in case group was 13.76 ± 2.78 dB while control group showed 13.69 ± 2.56 dB hearing threshold. This observation did not show any statistical difference in both groups.

TEOAE was performed in five frequency bands at 1, 1.5, 2, 3, and 4 KHz. The signal-to-noise ratio (S/N ratio) of TEOAE was studied and compared between case and control group. S/N ratio and average band reproducibility of both ears were found to be highly statistically significant at 3 and 4 KHz [Table 1].
Table 1: Data of TEOAE S/N ratio

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DPOAE was done in five frequencies at 2, 3, 4, 5, and 6 KHz. DPOAE S/N ratio of both ears showed highly significant difference at 5 and 6 KHz [Table 2].
Table 2: Data of DPOAE S/N Ratio

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Prolonged duration of hyperuricemia found statistically significant difference at 3 KHz in the left ear and 3–4 KHz in the right ear on S/N ratio of TEOAE [Table 3]. Similarly, hyperuricemic level also showed significant difference at 3 KHz in both ear on S/N ratio of TEOAE [Table 4].
Table 3: Association of TEOAE with duration of hyperuricemia

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Table 4: Association of TEOAE with serum level of uric acid

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Prolonged hyperuricemic duration had significant difference in S/N ratio of right ear at 5–6 KHz and left ear at 4–6 KHz in DPOAE [Table 5]. Similarly, higher uric acid level showed highly significant difference in S/N ratio in the right ear at 4–5 KHz and left ear at 4–6 KHz in DPOAE [Table 6].
Table 5: Association of DPOAE with duration of hyperuricemia

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Table 6: Association of DPOAE with serum level of uric acid

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  Discussion Top


Cochlea is the busiest receptive organ of the body that never fatigue although receiving meager blood supply by terminal and tenuous vascular channels through apex to base pattern. This blood supply pattern makes the basal turn vulnerable to vascular injury and thus effecting higher frequencies. Further, this micro-vascularity and highly sensitive fluid balance carry high risk of injury to hair cell, a highly sensitive basic unit of the cochlea.

There are numerous direct or indirect causes of cochlear injury that commonly include infections, ototoxicity, noise exposure, Meniere's disease, hypertension, hyperlipidemia, diabetes, hypothyroidism, and renal failure. These diseases cause vascular insult or metabolic changes in cochlear fluid, leading to widespread cochlear damage but individuals may remain asymptomatic. There are several hypothesis and experimental evidence to delineate actual site of injury in cochlea, and stria vascularis has been the most common site in the majority of etiologies.

Uric acid is the final product of purine metabolism, and its metabolic disorder leads to hyperuricemia with plasma uric acid levels >408 μmol/L (6.8 mg/dL). This is the upper limit of urate solubility in the serum and hence precipitation and crystal formation that further lead to inflammatory response with accumulation of interleukins and neutrophils.[12] As we are aware that any type of inflammatory response leads to increased vascular supply and edema subsequently, this inflammation forms a vicious cycle leading to decrease in blood supply by vascular injury and spasm. Later even in the healing phase, vascular injury continues by fibrotic changes in the tissue.

In this study, we found significant correlation with duration of hyperuricemia and OAE. There were significant differences in TEOAE S/N ratio and average band reproducibility at 3 and 4 KHz in case and control groups. Similarly, difference between DPOAE S/N ratio was highly significant at 5 and 6 KHz. These observations suggest effect of disease on cochlea in basal to apex pattern. These observations were similar to study by Hamed and El-Attar,[13] who measured common carotid artery intimal thickness and intracranial (middle cerebral and vertebral artery) blood flow through transcranial Doppler study. They found significant correlation in hyperuricemia, carotid intimal thickness, intracranial blood flow, and OAE. They concluded that hyperuricemia leads to atherosclerosis and cochlear damage, especially in basal turn. They stated that atherosclerosis and direct hair cell stiffness are possible explanations regarding hyperuricemia-related hearing impairment.

Although hyperuricemia has been implicated an independent risk factor for the development of hypertension and renal and cardiovascular diseases,[14],[15] a systemic review by van Durme et al.[5] found a weak association between hyperuricemia and cardiovascular risk. We nullified the effect of cardiovascular diseases by excluding individuals with a history of metabolic diseases (hyperlipidemia, diabetes, and renal disease) and hypertension. The present study endorses the hypothesis of atherosclerosis given by Hamed and El-Attar [13] although we did not evaluate intracranial vessels as we believe that atherosclerosis of small vessels, rather than major vessel, causes stria vascularis injury. Moreover, we believe that decreased intracranial blood flow should cause widespread injury, leading to severe-profound auditory dysfunction. Hence, in our opinion, besides small vessel atherosclerosis, urate crystal formation in the cochlear fluid has a major role as it leads to inflammatory response and terminal vascular spasm that damages outer hair cell damage. However, this hypothesis also needs further experimental studies, especially histopathological studies and high-resolution angiographic studies. This study also had a small sample size, and a large sample would have given more accurate results. Hence, further studies are needed to know the exact association of hyperuricemia and hearing loss.


  Conclusion Top


This study found hearing loss at high frequencies in hyperuricemia. In our hypothesis, crystal formation in hyperuricemia causes direct cochlear damage through inflammatory process besides minor vessels atherosclerosis. We advocate that irrespective of pathogenesis, all hyperuricemic patients should be screened and followed up by OAE so that appropriate interventions can be initiated before the patient becomes symptomatic.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
  References Top

1.
Oron Y, Elgart K, Marom T, Roth Y. Cardiovascular risk factors as causes for hearing impairment. Audiol Neurootol 2014;19:256-60.  Back to cited text no. 1
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2.
Andrés M, Quintanilla MA, Sivera F, Sánchez-Payá J, Pascual E, Vela P, et al. Silent monosodium urate crystal deposits are associated with severe coronary calcification in asymptomatic hyperuricemia: An exploratory study. Arthritis Rheumatol 2016;68:1531-9.  Back to cited text no. 2
    
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Lucertini M, Moleti A, Sisto R. On the detection of early cochlear damage by otoacoustic emission analysis. J Acoust Soc Am 2002;111:972-8.  Back to cited text no. 7
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Long GR, Tubis A, Jones KL. Modeling synchronization and suppression of spontaneous otoacoustic emissions using Van Der Pol oscillators: Effects of aspirin administration. J Acoust Soc Am 1991;89:1201-12.  Back to cited text no. 8
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Ravecca F, Berrettini S, Bruschini L, Segnini G, Sellari-Franceschini S. Progressive sensorineural hearing loss: Metabolic, hormonal and vascular etiology. Acta Otorhinolaryngol Ital 1998;18:42-50.  Back to cited text no. 9
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Suzuki K, Kaneko M, Murai K. Influence of serum lipids on auditory function. Laryngoscope 2000;110:1736-8.  Back to cited text no. 10
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Marcucci R, Alessandrello Liotta A, Cellai AP, Rogolino A, Berloco P, Leprini E, et al. Cardiovascular and thrombophilic risk factors for idiopathic sudden sensorineural hearing loss. J Thromb Haemost 2005;3:929-34.  Back to cited text no. 11
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Keenan RT, Nowatzky J, Pillinger MH. Etiology and pathogenesis of hyperuricemia and gout. In: Firestein GS, Budd RC, Gabriel SE, Mcinnes IB, O'Dell JR, editors. Kelley's Textbook of Rheumatology. 9th ed., Vol. 2. Philadelphia, PA: Elsevier Saunders; 2013. p. 1533-53.  Back to cited text no. 12
    
13.
Hamed SA, El-Attar AM. Cochlear dysfunction in hyperuricemia: Otoacoustic emission analysis. Am J Otolaryngol 2010;31:154-61.  Back to cited text no. 13
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Grassi D, Desideri G, Di Giacomantonio AV, Di Giosia P, Ferri C. Hyperuricemia and cardiovascular risk. High Blood Press Cardiovasc Prev 2014;21:235-42.  Back to cited text no. 14
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Abeles AM. Hyperuricemia, gout, and cardiovascular disease: An update. Curr Rheumatol Rep 2015;17:13.  Back to cited text no. 15
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    Tables

  [Table 1], [Table 2], [Table 3], [Table 4], [Table 5], [Table 6]



 

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