SUBCLINICAL PERIPHERAL NERVE AFFECTION IN CASES OF SUBCLINICAL HYPOTHYROIDISM

SUBCLINICAL PERIPHERAL NERVE AFFECTION IN CASES OF SUBCLINICAL HYPOTHYROIDISM

By

Hossam Abd El-Monem Ali

Department of Neurology, Faculty of Medicine, Al Azhar University, Damietta Branch

ABSTRACT

Background: One of the most frequent etiologies of endocrinal polyneuropathy is the hypothyroidism, that can cause axonal and demyelinating polyneuropathies.

Objective: To evaluate Subclinical affection of peripheral nerve among patient with subclinical hypothyroidism.

Patients and methods: Fifty consecutives recently diagnosed sub clinical hypothyroid patients referred from outpatients’ clinic of Internal Medicine Department to Neurophysiology unit of Neurology Department of Al-Azhar University hospital in new Damietta, and fifty age and gender matched euthyroid healthy persons The electrophysiological study of all studied groups was done including motor and sensory nerve conduction studies of both median, ulnar, peroneal and sural nerves.

Results: As regard to motor conduction study. There was a significant deference between both groups as regard of CMAP amplitude of both peroneal nerves, conduction velocity of both median and both peroneal nerves. Regarding to sensory conduction study there was significant deference between both groups as regard of of sensory terminal latency, SNAP amplitude of both median and sural nerves. There was a significant negative correlation between TSH serum level and each of conduction velocity of both median, both peroneal, left ulnar nerves, compound motor unit action potential amplitude of both peroneal nerves, and sensory nerve action potential amplitude of right sural nerve. There was a significant +ve correlation between the TSH serum level and terminal latency of both peroneal and right sural nerves.

Conclusion: Subclinical hypothyroidism can be considered as risk factor of peripheral nerve affection as in cases of hypothyroidism

Keywords: subclinical hypothyroidism, electrophysiological study, endocrinal polyneuropathy.

INTRODUCTION

     One of the most frequent etiologies of endocrinal polyneuropathy is the hypothyroidism that can cause axonal and demyelinating polyneuropathies. The diagnosis of neuropathy can be confirmed by electrophysiological examination in most of them, and the clinical manifestation occasionally observed in hypothyroid patients. Subclinical changes in conduction of motor and sensory fibers are relative common., The influence of subclinical hypothyroidism on peripheral nerves is undefined (Abdelazeem et al., 2017). The electrophysiological test is very sensitive test for diagnosis of neuropathy among hypothyroid patients (Waghmar et al., 2016).

     The pain of polyneuropathy affects the life quality of patients, and the pain killer drugs remain disappointing (Jaiswal and Dhankad, 2020). Treatment of the possible cause was considered as the appropriate therapy. Hormonal treatment can reverse the clinical and electrophysiological finding of neuropathy in cases with subclinical hypothyroidism (Jaiswal and Dhankad, 2020). The overall prevalence of subclinical hypothyroidism is 4-10% (ALEidan et al., 2018). The subclinical hypothrodism is common in elderly and affecting females more than males.The prevelance among genral population is 2.5-10%, and the prevalence of peripheral neuropathy among the hypothyroidism is 10-70% (Silva and Costa, 2013). The possible mechanism of neuropathy is focal demyelination or axonal degeneration. The subclinical hypothyroidism can be a possible. etiology of neuropathy and hormonal replacement therapy can improve this condition (Jaiswal and Dhankad, 2020).

     The most prevalent disorder preceding the manifest hypothyroidism is subclinical hypothyroidism. This can be diagnosed when normal titraiodothyroxin (T3) & free thyroxin (T4) serum level but TSH of high serum level. The thyroid hormons have a role in myelination, development and growth of neurons (Jaiswal and Dhankad, 2020).

     The electrophysiological studies showed affected measurements in patients with subclinical hypothyroidism, and the studies in assessment of nervous system (central and peripheral) in patients with sub clinical hypothyroidism is few and contra- versed (Jaiswal and Dhankad, 2020).

     The subclinical hypothyroidism can be defined as asymptomatic or oligo- symptomatic condition with high thyroid stimulating serum level and normal free thyroxin serum level. Sub clinical hypothyroidism representation is common in outpatient clinic by a specific symptoms like paresthesia, sexual dysfunction, chronic fatigue, psychiatric symptoms, myalgia, and mild cognitive impairment or asymptomatic (Silva and Costa, 2013).

     The aim of the study was to evaluate the subclinical peripheral nerve affection among patients with subclinical hypothyroidism.

PATIENTS AND METHODS

     Fifty consecutives recently diagnosed sub clinical hypothyroid patients referred from outpatients’ clinic of Internal Medicine Department to Neurophysiology unit of Neurology Department of Al-Azhar University Hospital in new Damietta, and 50 age and gender matched euthyroid healthy persons attended to the out patients as relatives to our stuff and students. the study was ethically approved by the Institutional Review Board of Damietta Faculty of Medicine, Al-Azhar University, and we excluded from our study the subject who have systemic diseases causing neuropathy, like: diabetes, renal impairment, manifest thyroid dysfunction, liver impairment, dyslipidemia, rheumatoid arthritis, malignancy, history of alcoholism, vitamin deficiency, and drug induced neuropathy like chemotherapy. The demographic criteria were studied including the age and gender.

     The test of thyroid function was included measurement of serum TSH, free T3, and free T4, Subclinical hypothyroidism (SCH) was defined when serum thyroid-stimulating hormone (TSH) level above the upper limit of normal despite normal levels of serum free thyroxine) (Silva and Costa, 2013).  The subclinical hypothyroidism was diagnosed when TSH level exceeded the normal range) 0.27-4.5 uIU/ mL), and FT4 within normal range (0.93-1.7ng/dL).

     The electrophysiological study of subjects was conducted using Nihon Kohden Machine, model UT-0800 J, Box BOARD (2CH) for JB-942BK (Japan).

     Terminal latency (TL), conduction velocity (CV) and amplitude of Compound Motor Action Potential (CMAP) through electrical stimulation of  ulnar and median nerves using supramaximal nerve stimulation delivered by bipolar electrical stimulator (at wrist and elbow ), and recording the evoked response form abductor digiti minimi and abductor policies brevis  using two service electrode (active and reference) the active on the belly of the muscle and the reference 3 cm distal the active electrode on metacarpophalangeal joint and the ground electrode placed between the stimulator and recording electrodes.

     Terminal latency, conduction velocity and (CMAP) amplitude through electrical stimulation of peroneal nerve using supramaximal nerve stimulation delivered by bipolar electrical stimulator (at ankle and neck of fibula) and recording the evoked response form extensor digitorium brevis muscle using two service electrode (active and reference) the active placed 7 cm anterior to lateral malleolus and the reference 3 cm distal the active electrode on metacarpophalangeal joint and the ground electrode placed between the stimulator and recording electrodes.

     Sensory terminal latency (STL), and (SNAP) through electrical stimulation of ulnar and median nerves using supramaximal nerve stimulation delivered by bipolar electrical stimulator at wrist and recording the evoked response form the little and middle fingers using two ring electrodes (active and reference) the active on 1st inter phalangeal joint and the reference on 2nd inter phalangeal joint and the ground electrode placed between the stimulator and recording electrodes. and electrical stimulation of sural nerve using supramaximal nerve stimulation delivered by bipolar electrical stimulator at the back of leg 12 cm above the lateral malleuolus and recording the evoked response form are behind the lateral malleuolus using two surface electrodes 3cm between the active and reference, and the ground electrode placed between the stimulator and recording electrodes.

     The neuropathy was diagnosed when the measurement exceeded the normal values according to Preston and Shapiro 2005 (Abdelazeem et al., 2017):

1. Motor median distal latency, conduction velocity and amplitude are ≤4.4ms, ≥ 49m/s & ≥4mv respectively.
2. Motor ulnar distal latency, conduction velocity and amplitude were

≤3.3ms, ≥ 49m/s & ≥6mv respectively.

3. Motor peroneal distal latency, conduction velocity and amplitude were ≤6.5ms, ≥ 42m/s & ≥2mv respectively.
4. Sensory median distal peak latency, conduction velocity and amplitude were ≤3.5ms, ≥ 50 m/s & ≥20uv respectively.
5. Sensory ulnar distal peak latency, conduction velocity and amplitude were ≤3.1ms, ≥ 50 m/s & ≥17uv respectively.
6. Sensory sural distal peak latency, conduction velocity and amplitude were ≤4.4ms, ≥ 40 m/s & ≥ 6uv respectively.

Statistical analysis: The collected data were analyzed using the SPSS vesion 25.

     The data were expressed as means and standerd deviation. Numerical data were compared by two sample Z test for means. Pearson Correlation Coefficient test were used for study the correlation between TSH level and parameters of nerve conduction study within the subclinical hypothyroidism group. And to identify the predictor of subclinical neuropathy we were used regression analysis test and the risk of estimation for detection of the risk factor of sub clinical neuropathy. P> 0.05 was considered significant.

RESULTS

     Both groups showed no significant differences as regard age distribution and T4 serum level, but TSH serum level showed significant differences between both groups.

     As regard to motor conduction study, there was a significant difference between both groups as regard of CMAP amplitude of both peroneal nerves, conduction velocity of both median and both peroneal nerves (Table 1).

Table (1):   Comparison between SCH and euthyroid groups as regard to motor conduction study of both median, ulnar and peroneal nerves

SCH =subclinical hypothyroidism. EU= euthyroid

     As regard to sensory conduction study, there was a significant difference between both groups as regard of sensory terminal latency, SNAP amplitude of both median and sural nerves (Table 2).

Table (2):   Comparison between SCH and euthyroid groups as regard to sensory conduction study of both median, ulnar and sural nerves

There is a significant -ve correlation between the TSH serum level and each of the following: 1) Conduction velocity of both median, both peroneal, and left ulnar nerves. 2) Compound motor unit action potential amplitude of both peroneal nerves. 3) Sensory nerve action potential amplitude of right sural nerve. There was a significant +ve correlation between the TSH serum level and terminal latency of both peroneal and right sural nerves (Table 3).

Table (3):   Correlation between TSH level and parameters of nerve conduction study within the subclinical hypothyroidism group

     The regression analysis for the significant correlated TSH serum level with electrophysiological parameters of examined nerves were suggestive of TSH serum level which was a significant predictor of affection of the following: 1) conduction velocity of both peroneal and left median nerves. 2) amplitude of compound motor unit action potential of both peroneal nerves and amplitude of sensory nerve action pintail of left sural nerves (Table 4).

Table (4):   TSH serum level as a predictor of affection of electrophysiological parameters of examined nerves

     The risk estimation of neuropathy among the subclinical hypothyroidism and euthyroid groups has shown the subclinical hypothyroidism which was considered as risk factor of neuropathy (Table 5).

Table (5):   Risk Estimate

DISCUSSION

     In our study, the comparison of age of the subclinical hypothyroidism and the euthyroid groups showed no significant difference in groups matched as age regards. Karne and Bhalerae (2016) found that 8% is the prevalence of peripheral neuropathy among the subjects aged ≥55 years, that mean the neuropathy increased as the age increase.

     Subclinical hypothyroidism group has a significant difference as regard of CMAP amplitude of both peroneal nerves, conduction velocity of both median, peroneal nerves, sensory terminal latency, SNAP amplitude of both median and sural nerves when compared with euthyroid group. The linear regression analysis confirmed that TSH level is independent predictor of neuropathy among the subclinical hypothyroidism group.

     Akarsu et al. (2013) mentioned a changes in electrophysiological measurements as a decrease in conduction velocity and CMAP amplitude and increased motor latency of the ulnar and median nerves. Balaraman et al (2013) reported that there is some electrophysiological changes in peripheral nerves of the subclinical hypothyroid females as well as that in early stages of hypothyroid females in comparison with healthy females.

     Jaiswal and Dhankad (2020) stated that Misiunas et al. (1995) concluded that neuropathy is present in subclinical hypothyroidism, and more evident when basal levels of TSH increased, also report there is electrophysiological measurements alteration in early stages of subclinical hypothyroidism similar to alteration in over myxedema patients, While Jalilzadh etal (2006) did not find any abnormality in peripheral nerves of patient with subclinical hypothyroidism.

     Gupta, et al 2016 state that Jalilzadeh et al (2006) reporting that there is no significant affection of peripheral nerves in subclinical hypothyroidism patients. Waghmar, et al, (2016) reported that Yuskel G et al (2007) found that electrophysiological abnormalities of the peripheral nerves in subclinical hypothyroidism.

     Penza et al. (2009) concluded that subclinical hypothyroidism can cause sensory neuropathy and can be treated with hormonal replacement therapy. Akarsu et al. (2013) mentioned a decrease in conduction velocity and CMAP amplitude and increased motor latency of the ulnar and median nerves.

     Waghmar, et al (2016) reported that hormonal and metabolic changes that occur in early stages of hypothyroidism can cause the abnormal electrophysiological measurements of the peripheral nerves. Jaiswal and Dhankad (2020) stated that hypothyroidism affect the peripheral nerves and this also to some extent can be seen with cases of subclinical hypothyroidism using neurophysiologic measures. And the hormonal replacement therapy can alleviate the motor bundle and neuromuscular junction affection. and they recommend further studies to conduct clinical evaluation. Allam et al. (2021) concluded that the subclinical hypothyroidism is highly prevalent in diabetic polyneuropathy and is independently related to severity. The role of subclinical hypothyroidism in neuropathy can be explained by many mechanisms: The subclinical hypothyroidism increases the oxidative stress, association to pronounced inflammatory state. Rashdat et al. (2022) concluded that the severity of clinical symptoms and sings of neuropathy among diabetic patient is related to subclinical hypothyroidism and recommend further studies.

CONCLUSION

     The subclinical hypothyroidism has role in peripheral neuropathy as in cases of hypothyroidism so the electrophysiological examination must be done for all cases of subclinical hypothyroidism for early diagnosis of neuropathy and early treatment.

REFERENCES

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تاثر العصب الطرفى تحت الاكلينيكى في حالات قصور الغدة الدرقية تحت الإكلينيكي

حسام عبد المنعم علي

¹قسم الأمراض العصبية، كلية الطب، جامعة الأزهر، دمياط

الخلفية: أحد أكثر المسببات شيوعًا لاعتلال الأعصاب الغدد الصماء هو قصور الغدة الدرقية، والذي يمكن أن يسبب اعتلال الأعصاب الطرفية.

الهدف من البحث: تقييم التأثير اتحت الاكلينيكى للعصب الطرفى بين مرضى قصور الغدة الدرقية تحت الإكلينيكي.

المرضى وطرق البحت: تمت إحالة خمسين مريض من مرضى القصور السريرى للغدة الدرقية الذين تم تشخيصهم حديثًا من العيادة الخارجية لقسم الباطنية العامة إلى وحدة الفسيولوجيا العصبية في قسم المخ والأعصاب بمستشفى الأزهر الجامعى بدمياط الجديدة ومجموعة ضابطة من الاصحاء من نفس اعمار المرضى وكان عددهم خمسون. وتم إجراء الدراسة الكهربية لجميع المجموعات المدروسة بما في ذلك دراسات التوصيل العصبي الحركي والحسي لكل من الاعصاب التالية:الوسيط، والزندي، والشظوي، والربيلى.

نتائج البحث: كان هناك فرق ذو دلالة احصائية بين المجموعتين فيما يتعلق بسعة جهد العصب الحركى للعصب الشظوى، وكذلك سرعة التوصيل للعصب الاوسط ر و الشظوي. وكان هناك فرق ذو دلالة احصائية بين المجموعتين فيما يتعلق بزمن الكمون الطرفي الحسي و سعة جهد العصب الحسي لكلا من العصب الوسط والربيلي، و كان هناك ارتباط سلبي ذو دلالة احصائية بين مستوى الهرمون المنشط للغدة الدرقية فى الدم وكلا من سرعة التوصيل للعصب الاوسط، والشظوي، و الزندي اليسرى، و سعة جهد العصب الحركى للعصب الشظوى، و سعة جهد العصب الحسي للعصب الربلي الأيمن. وكان هناك ارتباط إيجابي كبير بين مستوى الهرمون المنشط للغدة الدرقية فى الدم و فترة الكمون الحركى لكل من العصب الشظوى بالساقين والعصب الربيلى للساق اليمنى.

الاستنتاج: يمكن اعتبار قصور الغدة الدرقية تحت الإكلينيكي عامل خطر لتأثر الأعصاب الطرفية كما هو الحال في حالات قصور الغدة الدرقية.

الكلمات الدالة: قصور الغدة الدرقية تحت الإكلينيكي، دراسة الفيزيولوجيا الكهربية، اعتلال الأعصاب الغدد الصماء.