Brainstem Evoked Potential in Newly Diagnosed Patients of Subclinical Hypothyroidism

Abstract

Background:

Hypothyroidism is known to be associated with impairment of hearing. The hearing impairment may be conductive, sensorineural, or mixed.

Aims:

The aim is to assess the auditory pathway by brainstem auditory evoked potentials (BAEPs) in newly diagnosed patients of subclinical hypothyroidism and healthy sex- and age-matched controls.

Materials and Methods:

The study included 25 healthy sex- and age-matched controls (Group I) and 25 patients of newly diagnosed subclinical hypothyroidism (Group II). The recording was taken by using RMS EMG EP MK2 equipment. The unpaired Student's t-test was used and a P value <0.05 was considered significant.

Results:

Wave V of right ear BAEP in group II was prolonged (6 ± 0.62 ms) compared to group I (5.49 ± 0.26 ms), and wave V of left ear BAEP in group II was prolonged (5.84 ± 0.57 ms) compared to group I (5.47 ± 0.35 ms). There was no significant coefficient of correlation between wave V and inter-peak latency (IPL) I-V compared to thyroid-stimulating hormone (TSH) levels of both the ears.

Conclusion:

The prolongation of wave V in BAEPs of both ears suggests that the central auditory pathway is affected significantly in subclinical hypothyroid patients.

Introduction

Hypothyroidism is known to be associated with impairment of hearing. Kemp in 1907 was the first to document these symptoms in myxedema, where he found hearing impairment in a severely hypothyroid female patient.[1] Audiometrically, the extent of hearing loss in acquired hypothyroidism was first documented by Hilger.[2] Reports by some workers have shown that there is prolongation of both peripheral and central conduction time in hypothyroidism, while other studies suggest that changes in brainstem auditory evoked potential (BAEP) are not statistically significant. The hearing impairment may be conductive, sensorineural, or mixed. Ozata et al. observed that subclinical hypothyroidism did not lead to any alteration in BAEP,[3] while Cristiane et al. observed increases in inter-peak latency (IPL), namely, IPL I-III, IPL III-V, and IPL I-V in the subclinical group compared to IPL I-III, IPL III-V, and IPL I-V in the control group.[4]

Using BAEP is one of the methods for assessing the auditory pathway in the brainstem.[5] BAEPs are potentials recorded from the mastoid region and vertex in response to a brief auditory stimulation given to assess the conduction through the auditory pathway up to the midbrain. When a sound reaches the cochlea, it is converted into an electrical impulse and passes from the cochlea to the auditory cortex through the following pathway: Spiral ganglion in the cochlea → ventral and dorsal cochlear nuclei in brainstem → superior olivary nucleus in medulla → lateral lemniscus in midbrain → inferior colliculus in midbrain → medial geniculate body in thalamus and ultimately to auditory area in cerebral cortex. The normal BAEP recording consists of five or more vertex positive and vertex negative waves arising within 10 ms of auditory stimulus.[6]

Some workers have reported the prolongation of both peripheral and central conduction time in hypothyroidism, while other studies showed that there was no statistically significant alteration in BAEP in hypothyroidism.[5,7,8] Also, only a few studies have been performed to access auditory functions in subclinical hypothyroid patients using BAEP, and that, too, is conflicting.[3,4] Thus, the present study was planned to evaluate the auditory functions in subclinical hypothyroidism patients by BAEP.

Materials and Methods

The present study was conducted at the Department of Physiology, in collaboration with the Department of Endocrinology of a tertiary care center of North India. The study included 25 healthy age- and sex-matched controls and 25 patients of newly diagnosed subclinical hypothyroidism. Informed consent was taken from the patients as well as controls before doing BAEP testing on them. The subjects were divided into two groups:

Group I: 25 healthy control subjects of either sex, in the age group below 50 years (38 mean ± 6.6 standard deviation in years).

Group II: 25 newly diagnosed patients of subclinical hypothyroidism of either sex, in the age group below 50 years (36 mean ± 11 standard deviation in years).

Inclusion criteria

Subclinical hypothyroidism: Thyroid-stimulating hormone (TSH) level >5.1 mIU /L and T₄ ≥ 57.9 nmol /L (chemiluminescence immunoassay method).[9]

Exclusion criteria

• Neurological or psychiatric illness

• Altered sensorium

• Patients who do not cooperate during the study period

• Patients with any other major medical disorder that can affect hearing i.e., diabetes mellitus, anemia, hypertension, chronic obstructive pulmonary disease, acute or chronic liver disease, and acute or chronic kidney disease

• History of drug abuse, including alcoholism

BAEP

Equipment setup for BAEP study

The recording was taken by using RMS EMG EP MK2 equipment (Chandigarh, India).

Stimulus parameter

An auditory stimulus of intensity 60 dB above the normal hearing threshold was presented to both the ears monaurally after checking their normal hearing threshold. During stimulation of one ear, the other ear was masked by a 40-dB sound. In total, 1000 stimulations were applied. Stimuli were applied at the rate of 10/s. Signals were filtered with band-pass 100 Hz and 3 KHz.[5]

Recording electrodes for BAEP

The volume-conducted evoked responses were picked up from the scalp by using Ag/AgCl electrodes placed as per the International 10-20 system of placement.[10,11] We recorded the BAEPs by monoaural stimulation, so two montages Cz - A1 and Cz - A2 were used.[12]

Recordings of BAEPs

A normal BAEP recording consists of five or more vertex positive and vertex negative waves arising within 10 ms of the auditory stimulus.[12] Absolute peak latencies of waves I, II, III, IV, and V together with IPLs of I-III, I-V, and III-V; and amplitudes of wave I and V were recorded. Amplitudes were very variable and difficult to use clinically. Therefore, they were not considered in our study.[13] For BAEPs, the polarity was such that positivity was upward and negativity was downward.[14]

Statistical methods

To compare results between the two groups, unpaired Student's t-test was used using Microsoft Word and Excel and SPSS software (SPSS Inc., Chicago, USA). P value <0.05 was considered significant.

Results

The age of Group I (38 ± 6.6 years with the range of 28-50 years) was comparable with Group II (36 ± 11 years with the range of 11-50 years). There were three males and 22 females in Group I compared to four males and 21 females in Group II [Table 1].

Table 1.

Anthropometric parameter comparison between control (Group I) and newly diagnosed subclinical hypothyroid patients (Group II)

The body mass index (BMI) of Group I (24.18 ± 2.85 Kg/m², range 19.53-31.22 Kg/m²) was comparable with Group II (25.12 ± 5.56 Kg/m², range 13.52-33.33 Kg/m²) as shown in Table 1. The thyroxine (T4) level of group I was statistically different (P < 0.05) from Group II, while a very high statistically significant difference was seen between TSH values (P < 0.001) [Table 2].

Table 2.

Comparison of hormone levels between control (Group I) and newly diagnosed subclinical hypothyroid patients (Group II)

The difference in the right ear absolute peak latency of wave V between two groups was statistically significant (P < 0.05), though there was no significant difference in latencies of other waves and IPLs [Table 3].

Table 3.

Comparison of right ear BAEP absolute latencies and inter-peak latencies (IPLs) of control (Group I) and newly diagnosed subclinical hypothyroid patients (Group II)

The difference in the left ear absolute peak latency of wave V between the two groups was statistically significant (P < 0.05), but there was no significant difference in latencies of other waves and IPLs [Table 4].

Table 4.

Comparison of left ear BAEP absolute latencies and inter-peak latencies (IPLs) of control (Group I) and newly diagnosed subclinical hypothyroid patients (Group II)

The coefficient of correlation between wave V and IPL I-V in comparison to TSH in both the ears was statistically insignificant (P > 0.05).

Discussion

The dysfunction of the central nervous system (CNS) and loss of hearing are part of the clinical picture of hypothyroidism.[8] The sensorineural variant of deafness is the most common otolaryngological manifestation of thyroid dysfunction. Earlier studies have reported prolongation of both central and peripheral conduction time in patients of hypothyroidism, while a few studies concluded that the difference between BAEP and hypothyroid patients suffering from hearing loss was not statistically significant.[15] Several studies have been done on the auditory function of hypothyroid patients but few on the subclinical form of the disease by auditory brainstem response (ABR).[4]

In the present study, we compared 25 healthy age- and sex-matched controls with 25 patients of newly diagnosed subclinical hypothyroidism and there was no significant difference in age, height, weight, BMI, plasma glucose, hemoglobin level, and lipid profile, thus the two groups were comparable.

Different waves of BAEP have different generator sources and hence these waves reflect the activity of their generators. Wave I represents peripheral nervous system involvement, as any change in it depicts the effect of hypothyroidism on the auditory nerve. Other absolute waves represent CNS involvement: Any change in them represents the effect of hypothyroidism on the brainstem, as generators of waves II, III, IV, and V are the cochlear nucleus, superior olivary nucleus, lateral lemniscus, and inferior colliculus, respectively.[12,16,17] IPL I-III measures the neuronal conduction of the acoustic nerve across the subarachnoid space into the core of the lower pons. IPL I-V measures central neuronal conduction from the proximal acoustic nerve through pons to midbrain. IPL III-V measures and indirectly reflects neuronal conduction from lower pons to midbrain.[12] Thus, BAEP testing may be a useful diagnostic tool in exploring early subclinical neurological dysfunctions due to hypothyroidism.

In the present study, wave V of right ear BAEP was significantly prolonged (P < 0.05) in subclinical hypothyroidism patients (6 ± 0.62 ms) compared to control (5.49 ± 0.26 ms). Wave V of left ear BAEP was significantly prolonged (P < 0.05) in subclinical hypothyroidism patients (5.84 ± 0.57 ms) compared to control (5.47 ± 0.35 ms). Ozata et al. in their study found no significant change in BAEP in the subclinical group compared to the control group.[3] On the other hand, Cristiane et al. observed significant increase in the absolute latency of waves III and V in the subclinical group compared to the control group.[4]

In the present study, there was no significant change in BAEP IPLs of both the ears between the subclinical hypothyroidism patients and the control group. Ozata et al. observed similar results,[3] while Cristiane et al. observed increase in IPL I-III, IPL III-V, and IPL I-V in the subclinical group compared to the control group.[4]

Thus, the present study confirmed the involvement of the central auditory pathway, evidenced by the increase in the latency of wave V in subclinical hypothyroidism patients. A statistically significant increase in the latency of wave V bilaterally in our study indicates that the inferior colliculus was affected.

In our study, there was no significant difference in correlation between TSH levels and wave V and I-V IPLs. The same was observed by Khedr et al. in their study.[18]

Conclusion

In our study, we included subjects with normal hearing without any clinical symptoms or sign of deafness, but the prolongation of wave V in BAEP of both ears suggests that the central auditory pathway is affected significantly in subclinical hypothyroid patients. BAEP testing, a simple and noninvasive method, can act as a clinically useful diagnostic tool in detecting peripheral (auditory nerves) and central neuropathy (brainstem). Thus, we recommend that these electrophysiological studies should be considered as a routine test to find out any CNS dysfunction as early as possible in newly diagnosed patients of subclinical hypothyroidism.