A study to detect abnormalities in nerve conduction velocities in newly diagnosed hypothyroid subjects and find its correlation with free T 4 levels in a rural population of eastern India

Prabir Sinha Roy; Arunima Chaudhuri; Suranjan Banerjee; Debasis Adhya; Sarit Kumar Chaudhuri

doi:10.4103/1319-6308.156371

ORIGINAL ARTICLE

Year : 2015 | Volume : 15 | Issue : 2 | Page : 187-192

A study to detect abnormalities in nerve conduction velocities in newly diagnosed hypothyroid subjects and find its correlation with free T ₄ levels in a rural population of eastern India

Prabir Sinha Roy¹, Arunima Chaudhuri², Suranjan Banerjee³, Debasis Adhya², Sarit Kumar Chaudhuri⁴
¹ Department of Physiology, Medical College and Hospital, Kolkata, India
² Department of Physiology, Burdwan Medical College and Hospital, Burdwan, West Bengal, India
³ Department of Physiology, RG Kar Medical College and Hospital, Kolkata, India
⁴ Department of Physiology, Sagar Dutta Medical College and Hospital, Kolkata, India

Date of Web Publication

6-May-2015

Correspondence Address:
Arunima Chaudhuri
Krishnasayar South, Borehat, Burdwan - 713 102, West Bengal
India

Source of Support: None, Conflict of Interest: None

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DOI: 10.4103/1319-6308.156371

Abstract

Background: Deposition of glycosaminoglycans in nerves and soft tissues surrounding them result in axonal degeneration and secondary segmental demyelination and forms the pathological basis of alterations in peripheral nerve function in thyroid hormone deficiency. Aims: To detect abnormalities in nerve conduction velocities (NCVs) in newly diagnosed hypothyroid subjects and find its correlation with free thyroxine (FT4) levels in a rural population of eastern India. Materials and Methods: This cross-sectional study was carried in a tertiary care hospital of eastern India on 50 newly diagnosed hypothyroid subjects, selected as study group and 50 healthy subjects as control. Screening tests for thyroid hormone (Serum thyroid-stimulating hormone [TSH] and FT4 were estimated) was done on 512 adults and among them 50 were hypothyroid. NCV analysis was performed. Results: TSH values were 50.04 μIU//ml ± 14.61 and FT4 values 0.56 ng/dl ± 0.15 in hypothyroids and TSH values were 2.17 μIU//ml ± 0.57 and FT4 values were 1.46 ng/dl ± 0.27 respectively in euthyroid subjects. Forty-one (82%) patients out of 50 hypothyroid patients had presented with symptoms of hypothyroidism. NCV parameters were higher in the Euthyroid group than the hypothyroid group. FT4 values were positively correlated with NCVs. Conclusions: Screening tests need to be implemented in Indian population for early detection of thyroid disorders and electrophysiological studies are to be conducted in hypothyroid subjects to detect peripheral neuropathy because early detection can reverse the condition by treatment.

Abstract in Arabic

تم قياس سرعة توصيل الأعصاب مت نيذلا ةيقردلا ةدغلا ىضرم ىدل يبصعلا ليصوتلا ةعرس يف تاهوشتلا نع فشكلل ةسارد )14 ت ( تايوتسم عم ةقلاعلا داجيأ و اثيدح مهتلااح صيخشت
T4دنهلا يقرش يف ةيفيرلا قطانملا ناكس يف ةرحلا
ىلإ اهب ةطيحملا ةوخرلا ةجسنلأاو باصعلأا يف ناكيلجونينما زوكولجلا بّيرت يدؤي :ةساردلا ةيفلخ ةيفرطلا باصعلأا ةفيظو يف ةيضرم تاريغت ىلإ يدؤي اّمم ؛نيلايملا ةلازإو يبصع يراوحم سّكنت.ةيقردلا ةدغلا نومره ىبف صقن و
مت نيذلا ةيقردلا ةدغلا ىضرم ىدل يبصعلا ليصوتلا ةعرس يف تاهوشتلا نع فشكلا :فادهلأا يف ةيفيرلا قطانملا ناكس يف ةرحلا )14 ت( تايوتسم عم ةقلاعلا داجيأو اثيدح مهتلااح صيخشتT4دنهلا يقرش
ىلع دنهلا يقرش يف ةيثلاثلا ةياعرلا ىفشتسم يف ةساردلا هذه تيرجأ :اهدارفأ و ةساردلا جهنمًاثيدح مهتلااح صيخشن مت نيذلا ةيقردلا ةدغلا ىضرم نم نيسمخ
ةدغلا نومرهل تاصوحف تمت دقو .ةطباض ةنيع اونوكيل ءاحصلأا نم نيرخآ نيسمخ رايتخأ مت امك امك .ةيقردلا ةدغلا ىضرم نم 50 مهنيب و ، ءاحصلأا نم 512 ىلع )4 ت فو رحلا 4ت(و ةيقردلا.
0.56 نانو غرام / دل= ) النتائج: كانت قيم هرمون الغدة الدرقية 50.04 ميكرو وحدة دولية // مل +_ 14.61 وكانت قيم هرمون ) ف ت 4
0.15 في الغدة الدرقية . وكانت قيم هرمون الغدة الدرقية 2.17 ميكرو وحدة دولية//مل = 0.57 وكانت قيم ف ت 1.46 نانوعرام / دل +
0.27 على التوالي عند مرضى الغدة الدرقية أظهر 41 مريضا ) 82 %( قدموا بأعراض قصور في الغدة الدرقية وكانت أعلى في مجموعة الضبط
مؤشر و قد ارتبطت قيم ت 4 إيجابيا مع سرعة التوصيل العصبي. MCV من مجموعة مرضى الغدة الدرقية
الاستنتاجات: تحتاح الفحوصات التي ستجري للكشف عن اضطرابات الغدة الدرقية الكشف عن الأعصاب المحيطة وبالكشف المبكر يمكن
وصف العلاج

Keywords: Hypothyroidism, peripheral neuropathy, screening tests

How to cite this article:
Roy PS, Chaudhuri A, Banerjee S, Adhya D, Chaudhuri SK. A study to detect abnormalities in nerve conduction velocities in newly diagnosed hypothyroid subjects and find its correlation with free T ₄ levels in a rural population of eastern India. Saudi J Sports Med 2015;15:187-92

How to cite this URL:
Roy PS, Chaudhuri A, Banerjee S, Adhya D, Chaudhuri SK. A study to detect abnormalities in nerve conduction velocities in newly diagnosed hypothyroid subjects and find its correlation with free T ₄ levels in a rural population of eastern India. Saudi J Sports Med [serial online] 2015 [cited 2023 Jun 5];15:187-92. Available from: https://www.sjosm.org/text.asp?2015/15/2/187/156371

Introduction

In India, about 42 million people suffer from thyroid disorders. ^[1],[2],[3] The thyroid hormones are essential for growth and development, myelination of neurons, metabolism and normal organ functions. It influences the functioning of nearly all organ systems throughout lifetime. ^{[1],[2],[3],[4],[5],[6]} In India amongst the adult population, the prevalence of hypothyroidism was recently studied in a study in Cochin. Among 971 adult subjects, the prevalence of hypothyroidism was 3.9%. The prevalence of subclinical hypothyroidism (ScHt) was 9.4%. In North Eastern region of India, the rate of hypothyroidism is high. In the Radio-Immuno Laboratory of N. L. Medicare and Research Centre, Guwahati, out of 2456 randomly analyzed blood samples over a period of 1-year revealed incidence of hypothyroidism of 10.9% and ScHt being of 13.1%. ^[1],[2],[3]

Subclinical Hypothyroidism affects 3-15% of the adult population. The prevalence of thyroid autoimmunity increases after age of 35 years. ScHt presents mainly in agoitrous form and with positive antibodies, suggesting autoimmunity as the cause. There is scanty literature on screening studies and prevalence of these disorders in all regions of India. ^{[1],[2],[3],[4],[5]}

The underlying problem in hypothyroidism is slowing of many physiologic processes and the clinical manifestations reflect that slowing. In hypothyroidism, there is accumulation of matrix glycosaminoglycans in the interstitial fluids. This is due to increased synthesis of hyaluronic acid. ^{[1],[2],[3],[4],[5],[6]} Deposition of glycosaminoglycans in nerves and soft tissues surrounding them result in axonal degeneration and secondary segmental demyelination and forms the pathological basis of alterations in peripheral nerve function in thyroid hormone deficiency. Thyroid hormone deficit or excess during development can have permanent, pervasive, and profound effects on adult neurological function. ^{[1],[2],[3],[4],[5],[6],[7]}

In studies by Yeasmin et al. in 2007 ^[5] on 70 subjects (40 hypothyroid rest euthyroid) most of the patients had higher sensory distal latencies (SDL) with lower sensory nerve conduction velocities (SNCV) which were more marked in severe cases. About 67.5% of hypothyroid patients had shown abnormal SNCV when compared to that of euthyroids.

Misiunas et al. ^[4] performed electrophysiologic studies to investigate such abnormalities in patients with normal serum total T4 and hyperresponsiveness of thyroid-stimulating hormone (TSH) to thyrotropin-releasing hormone (TRH), either with normal or high levels of basal circulating TSH. Subjects were divided in three groups: (i) Hypothyroidism Stage I (Group I) (n = 17, mean age = 39 ± 34 years), T4 = 9 ± 0.7 μg/dL, TSH = 4.3 ± 0.4 μU/mL, sTSH post-TRH (peak value) = 37.6 ± 1.6 μU/mL; (ii) hypothyroidism Stage II (Group II) (n = 10, mean age: 43 ± 6 years), T4 = 7.7 ± 0.8 μg/dL, TSH = 20 ± 5 μU/mL, TSH post-TRH > 50 μU/mL; (iii) control group (n = 20, mean age 41 ± 5 years), healthy subjects. TRH test consisted in the i.v. injection of 200 μg TRH (normal peak value up to 25 μU/mL, normal basal TSH <5.5 μU/mL. None of the patients had carpal tunnel syndrome or any other neurological or metabolic disturbances. They studied the distal motor latencies, motor and sensory amplitudes, and nerve conduction velocities (NCVs). The motor parameters were measured in the median and external sciatic popliteal nerves, and the sensory parameters in the median and sural nerves. In most cases, values were obtained from both right and left nerves. Motor parameters: No differences were found between all groups for conduction velocities (CV). In ScHt serum free thyroxine (FT4) levels are maintained within normal limits by elevated TSH concentrations. Thus, it seems reasonable to find no significant impairment in peripheral nerve function in ScHt. ^{[1],[2],[3],[4],[5],[6]}

The present study was conducted to detect abnormalities in NCVs in newly diagnosed hypothyroid subjects and find its correlation with FT4 levels in a rural population of eastern India. Higher incidences of ScHt have been reported in different Indian studies, as there is lack of mass awareness about hypothyroid disorders and poverty in rural belts where the patients present with advanced form of disease when they visit the physician for the first time. Early screening and diagnosis may improve neurological complications, as peripheral nerve function in thyroid hormone deficiency is reversible. Since peripheral nerve has the ability to regenerate, it has been proposed that therapeutic intervention with thyroxin replacement may prove efficacious in the treatment of neuropathy in hypothyroidism.

Materials and methods

This cross-sectional study was carried in a tertiary care hospital of eastern India on 50 newly diagnosed hypothyroid subjects, selected as study group and 50 healthy subjects as control. The study was conducted in a time span of 1-year after taking institutional ethical clearance and informed consent of the subjects.

Inclusion criteria

Subjects with body mass index (BMI) under 30 aged between 20 and 60 years were included in the study.

Exclusion criteria

Pregnant females, subjects suffering from neurological illness, patients suffering from systemic pathology causing peripheral neuropathy and persons engaged in an occupation that may cause peripheral neuropathy were excluded. Subjects with known current or past thyroid disorders were also excluded from the study.

Five hundred and twelve normal subjects without family history of thyroid disease were evaluated for symptoms and laboratory tests for thyroid dysfunction. Every fourth person (following exclusion and inclusion criteria) from the hospital medical, outdoor registry was invited to participate into the study.

Careful history was recorded followed by clinical examination. Socioeconomic history, educational status, awareness about thyroid hormone disorders was recorded along with the address. All subjects were from rural areas, and education level was up to primary school. None was aware of thyroid disorders, and all came from socioeconomically backward class. However, all were using iodized salt at home. All were nonvegetarians. Vital parameters were recorded followed by anthropometric measurements. None of the subjects were known hypothyroid and were not receiving any treatment. Serum TSH was estimated by "Quantitative Enzyme immunoassay (EIA) method" using RFCL-manufactured commercial "ELlSCAN-TSH"-kit. Estimation of serum FT4 was done by "Quantitative EIA method" using RFCL-manufactured commercial "ELlSCAN-FT4"- kit. If the patient's serum level of FT4 was below normal limits, and TSH was above normal value, they were included in study group and the control group (euthyroid subjects) consisted of subjects having normal FT4 and TSH values.

Nerve conduction velocity analysis was performed with computerized evoked potential/Electromyography Measuring System "MEB-9200 NIHON KOHDEN Neuropack."

The following nerves were studied:

Upper Limb: Median and ulnar nerve
Lower Limb: Tibial and sural nerve.

Equipment

Equipment used in electrophysiological assessment of nerve and muscle is similar in overall design and function. Most equipment is essentially a computer with interface card for signal acquisition and controlling a stimulator. The stimulator is a waveform generator controlled by a controller module in the computer. The acquisition equipment consists of amplifiers, wide-band filters and is external to the computer, itself. The output from the acquisition equipment is then fed to an analog-to-digital conversion module of the computer.

Nerve conduction study

Methods

Electrodes

For surface stimulation, the stimulator electrodes ^[7] are usually stainless steel and mounted 2-3 cm apart on a small hand-held two-pronged probe. By convention the cathode (negative pole) under which negative charges collect is black in color. The anode (positive pole) is denoted by a red color. In most situations the cathodes of the stimulating and recording electrodes are adjacent on the nerve being studied and the anodes face away from each other. (The electrodes are set up "black-to black" aids in troubleshooting if problems arise).

Electrode position

The stimulating electrodes are placed on the skin overlying the nerve at two or more sites along the course of the nerve. The recording electrodes are placed over the belly of the muscle, with the active electrode over the midbelly of the muscle, as close to the estimated endplate site as possible.

Stimulus characteristics

Stimulation of the nerve being studied is accomplished using a brief burst of direct current. Stimulators are of two types: Constant voltage and constant current. Constant current stimulation seems to provide the most consistent responses. Constant current stimulators vary the voltage of stimulation to compensate for changing skin impedance, providing a consistent current to the nerve being stimulated while constant voltage units vary the current to obtain consistent voltage to the nerve. Regardless of the type, the amount of current applied to the tissue is never more than about 100 mA. Stimulus duration is usually in the range of 50-300 ms.

Stimulus artifact can often be troublesome, especially in the case of sensory NCS. It can arise from numerous causes. Factors helpful in reducing stimulation artifact are: Cleansing recording and stimulation skin sites with alcohol, placing the ground electrode between stimulation and recording sites, ascertaining that good electrical contact exists at all contact points, reducing stimulation intensity and/or duration, and increasing the distance between stimulation and recording sites when possible.

Procedure

After all of the electrodes are in place, the instrument is set to deliver repetitive stimuli, usually at 1 Hz. The stimulus voltage is initially set to zero then gradually increased with successive stimuli. A compound muscle action potential (CMAP) appears that grows larger with the increasing stimulus voltage. Eventually, further increases in voltage do not cause any change in CMAP amplitude. A stable response is assured if the voltage is 25% greater than the voltage needed to produce the highest amplitude CMAP. Once a good recording is made, the trace is stored for later analysis and the stimulating electrode moved proximally to a second stimulus site. Most nerves are stimulated in two sites for motor nerve conductions, but some are stimulated in at least three locations along the course of the nerve.

Interpretation

The following measurements are made from the CMAP produces by stimulation at each site:

Latency from stimulation to onset of the CMAP
Latency from stimulation to peak of the CMAP
CMAP amplitude.

The distance between stimulus sites is measured, and the NCV calculated according to the following simple formula: NCV = Dist/(PL−DL).

Where Dist = distance, PL = proximal latency, and DL = distal latency. The final results are expressed as meters per second or m/s.

The computer software "Statistical Package for the Social Sciences (SPSS) version 16 (SPSS Inc. Released 2007. SPSS for Windows, Version 16.0. Chicago, SPSS Inc.) was used for analyzing data and P 0≤ 0.05* was considered statistically significant and P ≤ 0.001** was considered as highly significant. Unpaired t-test was used to compare NCV of euthyroid and hypothyroid subjects, and Pearson's correlation coefficient was used to find a relation between independent variable FT4 and NCVs of all the nerves studied.

Results

In our study, 50 Clinical Hypothyroid patients with BMI <30 Kg/m ² were included. TSH values were 50.04 μIU//ml ± 14.61 and FT4 values 0.56 ng/dl ± 0.15. They had no history of diabetes or any disease that may cause peripheral neuropathy, and they were never engaged in any occupation that might affect the nervous system. Among these 50 hypothyroid patients, 27 were female, and 23 were male. The control group consisted of 20 female and 30 male subjects. TSH values were 2.17 μIU//ml ± 0.57 and FT4 values were 1.46 ng/dl ± 0.27 respectively. The mean ages of Hypothyroid, and the Euthyroid group of subjects were 35.04 ± 8.99 years, and 35.38 ± 9.64 years, respectively and there was no significant difference regarding age and sex between the two groups. Forty-one (82%) patients out of fifty hypothyroid patients had presented with symptoms of hypothyroidism.

Nerve conduction velocity parameters were higher in the Euthyroid group than the hypothyroid group. The differences of Median Motor and Tibial Motor between these two groups are highly significant (t = 3.4822, P < 0.001) and (t = 6.8632, P < 0.001) respectively. The differences of Median Sensory, Ulnar Motor, Ulnar Sensory, Sural Sensory were significant; and the t values and P values are, (t = 2.5829, P = 0.0113), (t = 2.4266, P = 0.0171), (t = 2.1333, P = 0.0354), (t = 2.2831, P = 0.0246) respectively [Table 1].

Pearson's correlation coefficient was used to study the relation of FT4 and NCVs of different nerves of both upper and lower extremities in hypothyroid individuals. T ₄ values were positively correlated with NCVs [Table 2].

Table 1: Comparison between NCV values of the clinical hypothyroid and euthyroid subjects

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Table 2: Correlation between T4 value and NCV parameters of hypothyroid subjects

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Discussion

The neurological complications of hypothyroidism, including dementia, cerebellar ataxia, myopathy and entrapment neuropathy and peripheral neuropathy. ^[8],[9],[10] The present study was conducted to detect abnormalities in NCVs in newly diagnosed hypothyroid subjects and find its correlation with FT4 levels in a rural population of eastern India. Patients with hypothyroidism presented late to physicians in the present study. In a rural population of a developing country due to lack of mass awareness about thyroid deficiency disorders and poverty there is delayed diagnosis of thyroid deficiency disorders. Similar results have been found in previous studies. ^[1],[2],[3] In our study 50 Clinical Hypothyroid patients with BMI <30 kg/m ² were included. TSH values were 50.04 μIU//ml ± 14.61 and FT4 values 0.56 ng/dl ± 0.15. Among these 50 hypothyroid patients, 27 were female and 23 were male. The control group consisted of 20 female and 30 male subjects. TSH values were 2.17 μIU//ml ± 0.57 and FT4 values were 1.46 ng/dl ± 0.27 respectively. Forty-one (82%) patients out of 50 hypothyroid patients had presented with symptoms of hypothyroidism. NCV parameters were higher in the Euthyroid group than the Clinical Hypothyroid group.

A prospective cohort study was performed in adults with newly diagnosed thyroid dysfunction by Duyff et al. in 2000. ^[9] Patients were evaluated clinically with hand-held dynamometry and with electrodiagnosis. In hypothyroid patients 79% had neuromuscular complaints, 38% had clinical weakness (manual muscle strength testing) in one or more muscle groups, 42% had signs of sensorimotor axonal neuropathy, and 29% had carpal tunnel syndrome. 62% had clinical weakness in at least one muscle group that correlated with FT4 concentrations. Our patients were also newly diagnosed cases of hypothyroidism, and their NCV was significantly worse as compared to healthy controls. FT4 values were also positively correlated with NCVs in hypothyroid individuals.

Study by Yeasmin in 2007 ^[5] concluded that sensory neuropathy may be a consequence of hypothyroidism. Most of the patients had higher SDL with SNCV, which were more marked in severe cases. Our study also shows similar results. Signs and symptoms of peripheral neuropathy may include pain, burning sensation, or numbness and tingling in the area affected by nerve damage. ^{[1],[2],[3],[4],[5],[6]} It may also cause muscle weakness or loss of muscle control. ^{[1],[2],[3],[4],[5],[6]} Eighty-two percent of our hypothyroid subjects were symptomatic.

Due to apparently asymptomatic nature of the illness, the "American Thyroid Association" has recommended routine population screening of both sexes at age 35 years and then every 5 years thereafter for early detection and treatment of ScHt. ^[6] We had screened 512 subjects from our Medicine outpatient department and found 50 hypothyroid patients among them. Hence nearly 9.77% were hypothyroid. Similar results have been previously reported in Indian studies. ^[1],[2],[3] Early detection of peripheral neuropathy in these individuals may improve the complications by treating with thyroxin. So screening tests need to be made mandatory.

Conclusions

Screening tests need to be implemented in Indian population for early detection of thyroid disorders and electrophysiological studies are to be conducted in hypothyroid subjects to detect peripheral neuropathy because early detection can reverse the condition by treatment. Patients with hypothyroidism present late to physicians in a rural population of a developing country due to lack of mass awareness about thyroid deficiency disorders and poverty.

References

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