Seok Min Hong; Yeso Choi; Sung Min Park; Jae Yong Byun

doi:10.21790/rvs.2024.012

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Original Article
Comparison of the outcomes of treatment with oral diuretic with steroid and steroid only for acute low-tone hearing loss: a prospective randomized controlled trial: Seok Min Hong¹, Yeso Choi², Sung Min Park², Jae Yong Byun¹; Research in Vestibular Science 2024;23(3):95-100.
DOI: https://doi.org/10.21790/rvs.2024.012
Published online: September 15, 2024

¹Department of Otorhinolaryngology-Head and Neck Surgery, Kyung Hee University Hospital at Gangdong, School of Medicine, Kyung Hee University, Seoul, Korea

²Department of Otorhinolaryngology-Head and Neck Surgery, Hallym University College of Medicine, Hwaseong, Korea

Corresponding author: Seok Min Hong Department of Otorhinolaryngology-Head and Neck Surgery, Kyung Hee University Hospital at Gangdong, 892 Dongnam-ro, Gangdong-gu, Seoul 05278, Korea. E-mail: thecell20@gmail.com

• Received: July 24, 2024 • Revised: August 15, 2024 • Accepted: August 18, 2024

This is an open access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

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Abstract
INTRODUCTION
METHODS
RESULTS
DISCUSSION
ARTICLE INFORMATION
REFERENCES

Abstract

Objectives
This study aimed to compare the efficacy of a combined steroid and diuretic (isosorbide) treatment with that of steroid-only treatment in patients with acute low-tone sensorineural hearing loss (ALHL).
Methods
A total of 34 patients with ALHL were recruited between January 2018 and December 2019 and randomized into two groups: a steroid-with-diuretic (isosorbide) group and a steroid-only group. The steroid-with-diuretic group received oral methylprednisolone for 10 days and isosorbide for 14 days, while the steroid-only group received methylprednisolone for 10 days. Hearing outcomes were measured using pure-tone audiometry at 8 weeks posttreatment. The outcomes were the absolute hearing gain at low frequencies (125, 250, and 500 Hz) and the recovery rate, which was classified into complete, partial, unchanged, progressive, and fluctuating.
Results
Of 34 patients, 30 (15 in each group) were analyzed. No significant differences were observed in baseline characteristics between the groups. The steroid-with-diuretic group showed higher absolute hearing gains at all three low frequencies than the steroid-only group, but the differences were not statistically significant complete recovery was observed in 13 patients in each group, with partial recovery in two patients in the steroid-with-diuretic group and unchanged outcomes in two patients in the steroid-only group. No patient exhibited disease progression.
Conclusions
Although combined steroid and diuretic therapy yielded better hearing outcomes than steroid-only therapy, the differences were not statistically significant. Further studies with larger sample sizes and extended follow-up periods are necessary to confirm these findings.
Keywords: Sensorineural hearing loss; Diuretics; Steroids

INTRODUCTION

Acute low-tone sensorineural hearing loss (ALHL) is relatively common in clinical practice. Patients with ALHL present with autophony, low-pitched tinnitus, a feeling of fullness in the ear, and mild dizziness, accompanied by hearing impairment [1]. Although the pathophysiology of ALHL remains unknown, several authors have reported a relationship between ALHL and cochlear hydrops as well as autoimmune diseases [2,3]. Generally, ALHL has a better prognosis than idiopathic sudden sensorineural hearing loss (ISSNHL) and responds well to treatment [4,5]. However, the relatively frequent recurrence of hearing problems, resulting in long-term hearing loss and progression to Menière’s disease during long-term follow-up, remains a challenge in patients with ALHL [3,6].

Hearing often recovers after a relatively short period. However, steroids or diuretics have been used to treat patients with ALHL without spontaneous recovery [1]. Glucocorticoids such as dexamethasone, prednisone, prednisolone, and betamethasone are commonly used for the treatment of sudden hearing loss [7]. Diuretics are used to treat endolymphatic hydrops [8]. Isosorbide, an osmotic diuretic, has been used to reduce endolymph volume and improve hearing thresholds by increasing serum osmolality in patients with Menière’s disease [9]. Several studies have investigated combined treatment with steroids and diuretics in patients with ALHL [1,10], but those studies were all retrospective.

In this prospective randomized controlled trial, we aimed to compare the efficacy of a combination of steroids with diuretic (isosorbide) and that of steroid without diuretic use for treating patients with ALHL.

METHODS

Ethics Statement

This study was approved by the Institutional Review Board of Hallym University Dongtan Sacred Heart Hospital (No. 2018-08-003). All participants provided written informed consent in accordance with the Declaration of Helsinki.

Trial Design

This was a prospective randomized controlled and parallel design study.

Participants

Thirty-four consecutive patients with ALHL were recruited. The inclusion criteria were as follows: (1) complaints of ear fullness or hearing loss and sudden onset; (2) purely sensorineural hearing loss with normal tympanic membrane findings; (3) a sum of hearing thresholds at three low frequencies (125, 250, and 500 Hz) of 70 dB or more and sum of hearing thresholds at three higher frequencies (2, 4, and 8 kHz) of 60 dB or less based on a pure-tone audiogram; and (4) symptom onset within 10 days [1]. Patients were excluded if they had Menière’s disease, a history of episodic vertigo, sudden sensorineural hearing loss, diabetes mellitus, chronic renal disease, heart disease, or acute or chronic otitis media.

Interventions

All patients underwent an initial examination that included documenting their medical history, physical examination, otoscopic examination, pure-tone audiometry (PTA), speech audiometry, impedance audiometry, auditory evoked potential testing, immunological tests, and serological tests. The steroid-with-diuretic group received oral methylprednisolone (0.8 mg/kg/day) for 5 days, with the dose gradually tapered for the next 5 days, and isosorbide (60–90 mL of isosorbide solution) for 14 days. The steroid-only group received oral methylprednisolone for 10 days. Additionally, all patients in both groups received lafutidine (20 mg/day) for 7 days. All patients completed the prescribed medication regimen, even if their hearing improved during treatment, and underwent follow-up PTA at 8 weeks.

Outcomes

The primary outcome variable was absolute hearing gain (difference between pretreatment and posttreatment hearing thresholds) at the three low frequencies (125, 250, and 500 Hz) assessed at the 8-week follow-up. The secondary outcome variable was recovery rate, categorized into (1) complete recovery, defined as low frequencies hearing (125, 250, and 500 Hz) returning to within 20 dB of normal levels; (2) partial recovery, characterized by an improvement of 10 dB or more in the average hearing loss at low frequencies compared to the initial audiogram; (3) unchanged, where the final follow-up average hearing loss at low frequencies remained within 10 dB of the initial audiogram; (4) progression, indicating an increase of more than 10 dB in the initial audiogram; and (5) fluctuation, observed when the sum of hearing thresholds at the three low frequencies (125, 250, and 500 Hz) reached 70 dB or higher again following complete or partial recovery [1].

Randomization

This randomized trial consisted of two treatment groups: the steroid-with-diuretic group and the steroid-only group. The audiologist who performed the hearing tests was blinded to the prescribed drugs. Patients were randomly assigned to one of the two groups using a computer-generated list of random numbers.

Statistical Analysis

Statistical differences were analyzed using the Mann-Whitney U-test for continuous variables and the Fisher exact and chi-square test for categorical variables, with a p-value of <0.05 considered statistically significant.

RESULTS

A total of 34 patients with ALHL who met the eligibility criteria were screened at the otolaryngology outpatient clinic between January 2018 and December 2019. Four participants (two from each group) withdrew from the study during the follow-up period, and 15 participants in each group completed the full course of medication and attended the follow-up (Fig. 1).

There were no significant differences in the demographic characteristics or duration from onset to treatment (Table 1). Additionally, no significant differences were observed in baseline hearing profiles, including hearing thresholds at 125, 250, and 500 Hz, the mean of the three low frequencies (125, 250, and 500 Hz), and the mean of the three high frequencies (2,000, 4,000, and 8,000 Hz) between the two groups (Table 2). Speech audiometry, impedance audiometry, auditory evoked potentials, immunological, and serological test did not show any findings suggestive of other conditions in any patients from both groups.

Absolute Hearing Gain after Treatment

The absolute hearing gain was 25.7±7.8, 27.7±5.9 and 20.3±9.2 at 125, 250, and 500 Hz, respectively, in the steroid-with-diuretic group, which was higher than gain of 22.7±12.8, 25.0 ±10.0, and 17.7±10.8 dB, respectively, observed in the steroid-only group; however, the differences were not statistically significant (Table 3).

Hearing Recovery Rate

Table 4 shows patient outcomes 8 weeks after treatment. In the steroid-with-diuretic group, 13 patients completely recovered and two showed partial recovery; all patients showed more than partial recovery, with two showing fluctuations during the follow-up period. In the steroid-only group, 13 patients showed complete recovery and two showed no change; among them, two patients experienced fluctuation during the follow-up period. All results related to the hearing recovery rate showed no significant differences between the two groups, and no patients exhibited progression (Table 4).

DISCUSSION

Despite sharing similarities with idiopathic sudden deafness and Menière’s disease, ALHL is regarded as an independent disease [1,2,11]. ALHL symptoms may be less severe compared to those of ISSNHL and can sometimes recover spontaneously [1]. The prognosis of ALHL is generally better than that of ISSNHL. Steroid therapy remains the preferred initial treatment for ALHL, with some studies suggesting alternative treatment modalities. The rationale for steroid therapy in ALHL is based on its immunosuppressive and anti-inflammatory properties. In addition, glucocorticoids may reverse autoimmune hearing loss caused by endolymph sodium-potassium imbalance through increased strial sodium transport, thereby restoring proper endolymph ion balance [12,13]. Furthermore, diuretics have been used in the treatment of endolymphatic hydrops, which is the pathophysiology of Menière’s disease. The rationale for diuretic therapy stems from the belief that the pathophysiology of ALHL may be similar to that of endolymphatic hydrops [14]. Isosorbide has been widely used in Korea and Japan, and it has the advantage of having fewer side effects, such as electrolyte imbalance [15]. It has been shown to reduce the endolymph volume in guinea pigs [9]. Unlike glycerol, it does not permeate into the endolymph, resulting in a dehydrating effect over 6 hours without a rebound phenomenon. A dehydration test using isosorbide in Menière’s disease was reported to be useful [16]. In our study, one patient who took isosorbide experienced a mild headache, but no patients discontinued the medication due to side effects.

One study reported that corticosteroids did not improve hearing in patients with ALHL [17]. Another study found that combination therapy with steroids and diuretics was more effective than treatment with a steroid or diuretic alone in patients with ALHL [1]. However, Chang et al. [18] suggested that combination therapy with steroids and diuretics and steroid monotherapy achieved similar improvements in hearing thresholds among patients with ALHL.

In our study, no statistical differences were observed in hearing results between the two groups, but the steroid-with-diuretic group showed higher hearing gains at all three low frequencies than the steroid-only group. At the 8-week follow-up, the complete recovery rate was the same in both groups; however, among the two patients who did not achieve complete recovery, those in the steroid-with-diuretic group showed partial recovery, while those in the steroid-only group showed no change. Overall, the steroid-with-diuretic group demonstrated better outcomes.

Despite a lack of evidence supporting the efficacy of diuretics in Menière’s disease, a multicenter randomized study investigating the effects of isosorbide over 12 weeks revealed that the group receiving a combination of isosorbide and betahistine showed a significant reduction in the frequency of vertigo episodes compared to the group receiving betahistine alone. Although there were no significant differences in PTA and speech audiometry results between the groups, the group that received combination therapy with isosorbide and betahistine demonstrated improvements in hearing thresholds compared to baseline, whereas the group receiving betahistine alone did not show any improvement [19].

In our study, the complete recovery rate was 87.3%, which surpassed the rates reported in previous studies, and we also observed higher hearing gains [10,20,21]. Factors affecting the prognosis of acute hearing loss, such as ISSNHL, include the initial hearing threshold, timing of treatment initiation, presence of chronic diseases such as diabetes, and duration of follow-up. In our study, patients with diabetes and chronic renal disease were excluded, treatment was initiated shortly after symptom onset in contrast to previous studies, and a final hearing assessment was conducted at 2 months, which are factors that we believe influenced our results.

This study has some limitations. First, the number of patients included in the study was smaller than that in previous studies. As a prospective study, strict inclusion and exclusion criteria were applied, informed consent was obtained, and follow-up was conducted for more than 8 weeks, which limited the number of eligible patients for analysis. Second, although we documented patients with hearing fluctuations during the follow-up period, ALHL can recur multiple times and progress to Menière’s disease. Therefore, the final results at 8 weeks may have been slightly short for capturing outcomes.

Nevertheless, to our knowledge, this is the first randomized controlled trial to evaluate the significant effects of isosorbide in patients with ALHL. Further studies with a larger number of patients and a longer follow-up period are needed, including the evaluation of changes in subjective symptoms such as aural fullness and tinnitus.

ARTICLE INFORMATION

Funding/Support

This study was supported by 2018 Alvogen Korea.

Conflicts of Interest

No potential conflict of interest relevant to this article was reported.

Availability of Data and Materials

All data generated or analyzed during this study are included in this published article. For other data, these may be requested through the corresponding author.

Authors’ Contributions

Conceptualization: SMH, JYB; Formal analysis: SMH, YC, SMP; Investigation: YC, SMP, JYB; Writing–original draft: SMH; Writing–review & editing: SMH.

All authors read and approved the final manuscript.

Fig. 1.

Flow diagram illustrating the study protocol.

Table 1.

Demographics of patients

Characteristic	Steroid-with-diuretics group	Steroid-only group	p-value
No. of patients	15	15
Age (yr)	45.9 ±14.1	38.3 ±9.6	0.187^a
Sex, male:female	6:9	6:9	0.448^b
Side, right:left	4:11	7:8	0.225^b
Duration from onset to treatment (day)	2.9±2.2	3.2±2.3	0.775^a

Values are presented as number only or mean±standard error of the mean.

^a Mann-Whitney U-test,

^b chi-square test.

Table 2.

Baseline hearing profiles

Frequency (Hz)	Hearing level (dB)		p-value^a
Frequency (Hz)	Steroid-with-diuretics group (n=15)	Steroid-only group (n=15)	p-value^a
125	40.0±9.8	37.0±8.6	0.653
250	40.7±9.2	38.7±8.3	0.935
500	32.0±13.2	31.0±11.4	0.902
Mean three low frequencies (125, 250, 500)	37.6±10.0	35.6±9.1	>0.999
Mean three high frequencies (2,000, 4,000, 8,000)	16.3±10.3	13.0±9.0	0.436

Values are presented as mean±standard error of the mean.

^a Mann-Whitney U-test.

Table 3.

Comparison of absolute hearing gain threshold between steroid-with-diuretic group and steroid-only group according to frequency

Frequency (Hz)	Hearing level (dB)		p-value^a
Frequency (Hz)	Steroid-with-diuretics group (n=15)	Steroid-only group (n=15)	p-value^a
125 Hz	25.7±7.8	22.7±12.8	0.806
250 Hz	27.7±5.9	25.0±10.0	0.870
500 Hz	20.3±9.2	17.7±10.8	0.595

Values are presented as mean±standard error of the mean.

^a Mann-Whitney U-test.

Table 4.

Outcomes 8 weeks after treatment

Variable	Steroid-with-diuretics group (n=15)	Steroid-only group (n=15)	p-value^a
Complete recovery	13 (86.7)	13 (86.7)	>0.999
Partial recovery	2 (13.3)	0 (0)	0.483
Unchanged	0 (0)	2 (13.3)	0.483
Progression	0 (0)	0 (0)
Fluctuation	2 (13.3)	2 (13.3)	>0.999

Values are presented as number (%).

^a Fisher exact test.

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6. Fushiki H, Junicho M, Aso S, Watanabe Y. Recurrence rate of idiopathic sudden low-tone sensorineural hearing loss without vertigo: a long-term follow-up study. Otol Neurotol 2009;30:295–298.PubMed
7. Parnes LS, Sun AH, Freeman DJ. Corticosteroid pharmacokinetics in the inner ear fluids: an animal study followed by clinical application. Laryngoscope 1999;109(7 Pt 2):1–17.Article
8. Klockhoff I, Lindblom U, Stahle J. Diuretic treatment of Meniere disease: long-term results with chlorthalidone. Arch Otolaryngol 1974;100:262–265.Article PubMed
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Comparison of the outcomes of treatment with an oral diuretics with steroid and steroid only for acute low-tone hearing loss: a prospective randomized controlled trial

Res Vestib Sci. 2024;23(3):95-100. Published online September 15, 2024

DOI: https://doi.org/10.21790/rvs.2024.012

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Figure

Comparison of the outcomes of treatment with an oral diuretics with steroid and steroid only for acute low-tone hearing loss: a prospective randomized controlled trial

Fig. 1. Flow diagram illustrating the study protocol.

Fig. 1.

Comparison of the outcomes of treatment with an oral diuretics with steroid and steroid only for acute low-tone hearing loss: a prospective randomized controlled trial

Characteristic	Steroid-with-diuretics group	Steroid-only group	p-value
No. of patients	15	15
Age (yr)	45.9 ±14.1	38.3 ±9.6	0.187^a
Sex, male:female	6:9	6:9	0.448^b
Side, right:left	4:11	7:8	0.225^b
Duration from onset to treatment (day)	2.9±2.2	3.2±2.3	0.775^a

Frequency (Hz)	Hearing level (dB)		p-value^a
Frequency (Hz)	Steroid-with-diuretics group (n=15)	Steroid-only group (n=15)	p-value^a
125	40.0±9.8	37.0±8.6	0.653
250	40.7±9.2	38.7±8.3	0.935
500	32.0±13.2	31.0±11.4	0.902
Mean three low frequencies (125, 250, 500)	37.6±10.0	35.6±9.1	>0.999
Mean three high frequencies (2,000, 4,000, 8,000)	16.3±10.3	13.0±9.0	0.436

Frequency (Hz)	Hearing level (dB)		p-value^a
Frequency (Hz)	Steroid-with-diuretics group (n=15)	Steroid-only group (n=15)	p-value^a
125 Hz	25.7±7.8	22.7±12.8	0.806
250 Hz	27.7±5.9	25.0±10.0	0.870
500 Hz	20.3±9.2	17.7±10.8	0.595

Variable	Steroid-with-diuretics group (n=15)	Steroid-only group (n=15)	p-value^a
Complete recovery	13 (86.7)	13 (86.7)	>0.999
Partial recovery	2 (13.3)	0 (0)	0.483
Unchanged	0 (0)	2 (13.3)	0.483
Progression	0 (0)	0 (0)
Fluctuation	2 (13.3)	2 (13.3)	>0.999

Table 1. Demographics of patients

Values are presented as number only or mean±standard error of the mean.

Mann-Whitney U-test,

chi-square test.

Table 2. Baseline hearing profiles

Values are presented as mean±standard error of the mean.

Mann-Whitney U-test.

Table 3. Comparison of absolute hearing gain threshold between steroid-with-diuretic group and steroid-only group according to frequency

Values are presented as mean±standard error of the mean.

Mann-Whitney U-test.

Table 4. Outcomes 8 weeks after treatment

Values are presented as number (%).

Fisher exact test.