Thyroid-Stimulating Hormone and Free Thyroxine Alterations in Subjects with Occupational Hearing Loss.

CONTEXT AND AIM: Occupational hearing loss (OHL) is caused by exposure to industrial noise. Alterations in the thyroid-stimulating hormone (TSH) and free thyroxine (FT4) levels are related to hearing loss. The purpose of this study is to investigate the TSH and FT4 level alterations in OHL. METHODS AND MATERIAL: Among 428 subjects, 144 male workers with normal hearing (NH), noise-induced hearing loss (NIHL), and high tone loss (HTL) (N = 48 in each group) were included in this study. All the subjects had normal TSH and FT4 levels.
RESULTS: The TSH level is higher in the HTL and NIHL groups in comparison to NH, but it is only significant in the HTL group. The FT4 level is significantly lower in the NIHL group; however, the lower FT4 level in the HTL group is not significant when compared to the NH group. DISCUSSION: The NIHL group may turn into the HTL group over time. This process could be monitored by alteration in their TSH and FT4 levels.
CONCLUSIONS: Alterations in the TSH and FT4 levels could be considered as a pathophysiology for OHL. More research is required to investigate the electrophysiological, physiological, and histological correlations of TSH and FT4 and different types of hearing loss caused by noise exposure. Copyright:

INTRODUCTION

Occupational hearing loss (OHL) is a common hearing disorder which was the focus of many research studies.[12] The permanent effects of noise on the hearing system include damage to the structure of the outer hair cells (OHC), inner hair cells (IHC), and the mechanosensory function of the hair bundles in the cochlea as well.[3] The exact pathophysiologic mechanisms of the OHL is unclear.

Normal development of the auditory system requires the normal function of the thyroid hormone. The T3 and FT4 hormones have modulatory effects on many organs. They also control the secretion of TSH by negative inhibition in the hypothalamic-pituitary-thyroid (HPT) axis [Figure 1].[4] The thyroid hormones have multiple effects on the middle and inner ear. Insufficient FT4 level can shift the threshold in the action potential (AP) and cochlear microphonic (CM) potentials[5]; in some instances, it can affect the central auditory system.[6] Although extensive research has been done on the effects of the thyroid hormones on the development and function of the auditory system, the alterations in the levels of TSH and thyroid hormones on OHL were not studied directly.

Figure 1

Hypothalamic–pituitary–thyroid axis

Alterations in the thyroid hormones can be linked to different congenital and acquired hearing losses. It was reported that hypothyroidism simulation in rat offsprings induced severe hearing loss.[7] Also, some studies have revealed that the tuning curve of the auditory nerve flattened and the AP thresholds were elevated in rats with hypothyroidism.[8] Although no significant differences have been reported in hyperthyroid human patients, the thresholds for four frequencies in the range of the conventional audiometry (i.e., 1000, 2000, 4000 and 8000 Hz) were higher than 25 dB HL indicating the presence of the high tone hearing loss (HTL).[9] It was also reported that the Acoustic Stapedius Reflex (ASR) recovery time was increased and the maximal amplitude was decreased in hypothyroid patients whereas, in hyperthyroid patients, none of the recorded parameters of the ASR were statistically different from normal subjects.[10] In another study[11] on 23 hypothyroidism patients, 12 had definite hearing impairments. In a similar study, the hearing status of 94 congenital hypothyroid patients was evaluated using the auditory brainstem response (ABR) and otoacoustic emission (OAE). No hearing loss was reported in those patients who had high levels of the TSH.[12] On the other hand, the audiologic evaluation of the acquired hypothyroidism might result in high values of the TSH, which might be associated with more frequent cochleovestibular symptoms, including mild to moderate hearing losses, tinnitus, and vertigo. In 30 hypothyroidism patients, 22 ears had sensorineural hearing losses and the wave V absolute latency of ABR changed in 10 patients.[13]

Previous studies suggest controversies in the hearing profile of hypo and hyperthyroidism patients.[8911] Most of these studies had a low sample size. On the other hand, previous researches did not account for the evaluation of the thyroid hormones and TSH serum level in subjects exposed to industrial noises and little is known about the relationship between the thyroid hormones, TSH serum level, and OHL.

Although the association between environmental noise exposure and alterations in T3, FT4, and TSH have been reported in animal studies,[1415] it has not been investigated in human subjects.

MATERIAL AND METHOD

Participant

This research was a retrospective study in which 144 male subjects selected from the database of an occupational center between the age of 25 and 40 years (mean = 32.90, SD = 3.68). The subjects were categorized into three groups including normal hearing (NH), noise-induced hearing loss (NIHL), and high tone hearing loss (HTL). All subjects had no history of autoimmune disease and the anti-TPO level was less than 20 IU/ml. Subjects in the HTL group were diagnosed with NIHL in their previous medical records. Subjects in the NH group were not exposed to industrial noise based on their job position. The risk of noise exposure was categorized as moderate and high based on the noise map for the NIHL and HTL groups [Figure 2]. The NH group had audiometric frequencies equal or less than 25 dB hearing level (HL) in both the ears. The NIHL group were subjects who had notched-hearing losses in at least one ear at 3, 4, or 6 kHz. In the HTL group, the subjects had sloping hearing loss at 3, 4, 6, and 8 kHz. Only subjects within the normal range of the TSH and FT4 levels were selected to avoid any effects of hyper- or hypothyroidism. Iran University of Medical Sciences (IUMS) approved the ethical principles of the study protocol on 2018/09/23.

Figure 2

Risk of noise exposure in noise-induced hearing loss and high-tone loss groups in the study

Procedure

Hearing evaluation

Air conduction audiometric evaluation at 0.5, 1, 2, 3, 4, 6, and 8 kHz was conducted for all subjects (Pezhvak Ava Audiometer, Ultimate, Iran). Otoscopy was performed to ensure the external ear canal and the tympanic membrane are intact. (Welch Allyn, 11710, USA) The audiometric evaluation was done before 8 hours of work to exclude any temporary threshold shift.

Measurement of TSH and FT4

The blood samples of all subjects were collected. Fifty microliters for TSH and 25 microliters for FT4 measurements from each serum control and samples and 100 microliter enzyme conjugate solution for TSH and 50 microliters in addition to 50 assay buffers for FT4 were poured into the sinks. The plates were moved gently for 15 seconds and the drug was mixed with the contents properly. The sinks were hermetically sealed by special tags of the sink. The sinks were incubated for 60 minutes at room temperature. The sink content was evacuated and washed 5 times by special rinsing solution. For each measurement, 100 chromogen microliter substrates were poured into the sinks and incubated for 15 minutes in a dark room at 22–28 centigrade degrees. At last, by adding 100 microliters to the solution in the sinks, the enzymatic reaction was stopped. To evaluate the light absorbance for each sink, an ELIZA reader instrument with a 450 nm filter was used.

Statistical analysis

The Statistical Package for Social Sciences (SPSS) software v. 23 (SPSS Inc., Chicago, USA) was used for the analysis of data.

RESULTS

Figure 3 illustrates the descriptive analysis of data concerning the degree of hearing loss in the NIHL and HTL subjects. Pearson Chi-Square test shows there is no significant difference among the degree of hearing loss between the NIHL and HTL groups (p = 0.885, df = 2).

Figure 3

Degree of hearing loss among NIHL and HTL groups of the study. NIHL in a percent: Noise-induced hearing loss, HTL: High tone loss

The mean of the TSH and FT4 for all subjects are 1.91 mlU/L and 6.84 mcg/dL, respectively. None of the subjects had hyper- or hypothyroidism. The descriptive analysis of the data is summarized in Table 1. As the TSH level increased, the level of the FT4 decreased in all the study groups. This relationship is plotted in Figure 4.

Table 1

Analysis of the TSH and FT4 in study groups

Study Group		N	Mean TSH (mlU/L)	SD	Mean T4 (mcg/dL	SD
Normal Hearing		48	1.62	0.57	7.28	1.11
NIHL	Mild	17	1.78	0.60	6.36	1.14
	Moderate	16	1.88	0.66	6.25	0.88
	Severe	15	2.11	0.84	6.81	1.40
	All	48	1.91	0.70	6.47	1.16
HTL	Mild	19	2.01	1.06	7.32	1.32
	Moderate	14	1.83	0.79	7.16	0.99
	Severe	15	2.86	0.75	5.73	1.07
	All	48	2.22	0.98	6.78	1.34
Total		144	1.91	0.80	6.84	1.24

TSH: Thyroid-Stimulating Hormone, FT4: Free Thyroxine, NIHL: noise induced hearing loss, HTL: high tone loss

Figure 4

Scatterplots of TSH and FT4 in the study group showing their relationship. As the level of TSH increases, the level of FT4 decreases in all study groups

The dependent variable (hearing status) was nominal with three levels (NH, NIHL, and HTL) and the independent variables were continuous (TSH and FT4 levels). The study was designed to investigate the relationship between hearing status and the TSH and FT4 levels. A multinomial logistic regression test was administered to investigate this relationship. [Tables 2 - 4]

Table 2

Goodness-of fit in multinomial logistic regression of this study

	Chi-Square	df	Sig.
Pearson	291.259	282	0.340
Deviance	293.170	282	0.311

Table 4

Parameter estimates in multinomial logistic regression of this study

Catagory of Hearing Statusa		B	Sth. Error	Wald	df	Exp(B)	95% Confidence Interval for Exp(B)
							Lower Bound		Upper Bound
Noise Induced Hearing Loss (NIHL)	Intercept	3.304	1.745	3.586	1
	TSH Level	0.213	0.339	.394	1	1.237		0.637		2.402
	T4 Level	-0.536	0.204	6.868	1	0.585		0.392		0.874
Hight Tone Loss (HTL)	Intercept	-1.448	1.742	.691	1
	TSH Level	0.992	0.329	9.109	1	2.696	1.416		5.132
	T4 Level	-0.060	0.196	.094	1	0.942	0.641		1.383

a. The reference category is: Normal Hearing (NH).

The Chi-square statistic (291.259) and P values (0.340) indicate that the proposed model of the relationship between the TSH and FT4 level and hearing status fits the data well. Table 3 also shows that the model is significant as well as the P value is less than 0.05.

Table 3

Model fitting information in multinomial logistic regression of this study

Model	Model Fitting Criteria	Likelihood Ratio Tests
	-2 Log Likelihood	Chi-Square	df	Sig.
Intercept Only	316.400
Final	293.170	23.231	4	0.000

Table 5 shows that the level of TSH is significantly higher in the HTL group compared to the NH (p = 003); however, a higher TSH level in the NIHL group is not significant (p = 0.530). The level of the FT4 in both the NIHL and HTL groups were lower than those subjects in the NH group, but this decrease is only significant in the NIHL group (p = 0.009). These results indicate that the higher level of the TSH and lower level of the FT4 are more likely to be associated with the HTL and NIHL, respectively [Figure 5].

Table 5

ANOVA analysis showing the comparison of TSH and T4 levels in study groups

		Sum of Squares	df	Mean Square	F	Sig.
TSH Level	Between Groups	13.978	3	4.659	8.296	.000
	Within Groups	78.627	140	.562
	Total	92.605	143
T4 Level	Between Groups	19.810	3	6.603	4.603	.004
	Within Groups	200.842	140	1.435
	Total	220.652	143

a. The reference category is: Normal Hearing (NH).

Figure 5

Comparison of mean TSH and FT4 levels in three groups of NH, NIHL, and HTL Asterlike show significant values compared to the NH group. Error bars: 95% CI

To investigate any relationship between the subjects' hearing categories (i.e., normal hearing, mild, moderate, and severe hearing loss) with the TSH and FT4 levels, one-way ANOVA analysis showed a significant difference between groups (p < 0.05, F = 8.26 for TSH and F = 4.60 for FT4). Further investigations with Tukey post-hoc test showed a significantly higher level of TSH and also a significantly lower FT4 level in severe hearing loss. The mean of TSH and FT4 levels of different categories of subjects' hearing status is shown in Figure 6.

Figure 6

Mean TSH (a) and FT4 (b) levels of subjects with different levels of hearing in all subjects. Mean TSH (c-d) and mean FT4 (e-f) levels separately shown in NIHL and HTL subjects

DISCUSSION

The main cause of the OHL in adults is the occupational noisein developing countries.[16] Other pathophysiological mechanisms of the OHL are the subject of many studies.[12]

The thyroid hormones have a remarkable effect on the development of the auditory system. Many studies have investigated the relationship between the thyroid hormones and acquired hearing loss;[811] but there are inconsistent results between these studies. In a study, a significant difference in the TSH and thyroid hormone level with hearing loss is reported[9]; however, some authors demonstrated no such relationship.[12] This inconsistency could be due to methodological differences. The goal of this study is to evaluate the TSH and FT4 in subjects with OHL exposed to industrial noise.

In the present study, the serum TSH levels of the subjects with HTL (m = 2.22 mlU/L, SD = 0.98), NIHL (m = 1.91 mlU/L, SD = 0.70), NH (m = 1.62 mlU/L, SD = 0.57) were evaluated. The HTL group showed significantly higher TSH in comparison to NH (p < 0.05). In the NIHL group, although the level of TSH in comparison to NH was higher, it was not significant (p > 0.05). All subjects in this study had normal range of TSH. The high biological variations of the TSH observed only in the first weeks of life; therefore, this is not expected in adults until the variation becomes large enough.[17] The high variation of TSH in subjects with HTL indicates an abnormal biological variation that must be considered in clinical observation. The high value of TSH in the HTL group in the current study is in conjunction with the earlier reports. In a study, the hearing status of the hypothyroidism patients was evaluated using pure tone audiometry and ABR. 12 patients of the total 20 study subjects had high-tone sensorineural hearing loss, which is consistent with our results.[18] In another study, 14 hyperthyroid patients had normal hearing, but in 21 hypothyroid patients, the audiometric evaluation showed HTL with most hearing loss at 8 kHz.[9] In another report, the high values of TSH in comparison to control group were found in hypothyroidism patients who also had more frequent cochleovestibular symptoms including mild/moderate sensorineural hearing loss, tinnitus, and vertigo (p < 0.05). However, despite the high incidence of hearing loss and altered ABR findings, no significant difference between hearing loss and the serum level of TSH was reported (p > 0.05).[13] One possible reason for this inconsistent observation could be the gender of subjects. In the current study, all subjects were male; but in the aforementioned study, all of the subjects were female. There may be a difference between the hormone level and its alteration in male versus female.

The mean serum of the FT4 level in subjects with HTL (m = 6.78 mcg/dL, SD = 1.34), NIHL (m = 6.47 mcg/dL, SD = 1.16), and NH (m = 1.62 mcg/dL, SD = 1.11) is also evaluated. As is expected, the FT4 level of both NIHL and HTL groups was lower in comparison to NH, but is only significant in the NIHL subjects (p < 0.05). Statistical analysis revealed no significant difference among the degree of hearing loss between NIHL and HTL; therefore, it could not be considered for FT4 differences in our study. On the other hand, FT4 does not change significantly in adults[17]; thus, the significantly lower FT4 level in the NIHL group could not be considered biologically normal. This finding in OHL correlates with the previous finding suggesting that even a small variation of FT4 level could be considered as a risk factor for hearing defects such as idiopathic sensory-neural hearing loss.[19]

The TSH and FT4 variation in normal functioning thyroid and its association with OHL was not studied yet. Both NIHL and HTL groups in this study were diagnosed with OHL. The progressive nature of NIHL is well reported in the literature.[20] This progression could result NIHL to become HTL over time. The TSH level could confirm this statement as it had more value in NIHL and significantly higher value in HTL subjects. The FT4 level is significantly lower in NIHL subjects, and it is proposed that this elevation could be considered as a thyroid dysfunction as it is supposed to be more due to the higher TSH level of this group. Although, the thyroid function is likely to be within normal range as the NIHL progresses to HTL, but the level of the TSH become significantly high in HTL.

CONCLUSIONS

The results of this study indicates that the high variations of FT4 and TSH are more likely to be associated with NIHL and HTL, respectively. The low level of FT4 is correlated with NIHL and also, the high level of TSH is correlated with HTL. More studies on animal models and human are required to investigate the electrophysiological, physiological, and histological correlations of the TSH, thyroid hormones, and different types of hearing loss caused by noise exposure.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.