Silent central nervoussystem affectionincasesofsubclinical hypothyroidism

Silent central nervoussystem ffection incases of sub clinical hypothyroidism

By

Hossam Abd Elmonem Ali

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

ABSTRACT

Background: Hypothyroidism is one of the greatest endocrinal disorders that can affect the central nervous system

Objective: To assess silent affection of central nervous system among cases of subclinical hypothyroidism.

Patients and methods: A group of Fifty cases of sub clinical hypothyroidismreferredfrom outpatients’ clinic of Internal Medicine Department to Neurophysiology unit of Neurology Department of Al-Azhar University hospital in new Damietta, and  another euthyroid  group of fifty, age and gender matched healthy persons. The electrophysiological study of both groups was done including Electroencephalography and evoked potentials (auditory and visual).

Results: As regard to EEG, Eighteen patients (36%) had EEG abnormalities. thir teen patients (26%) had diffuse slowness of background activity formed mainly of theta wave activity with or without paroxysmal high voltage theta or delta wave activity (16%).Auditory evoked potentials (ABR)showed significant prolongation, of  III &V wave latencies ,  and inter peak latencies of

I-V, & III-V among the subclinical group on comparison with the control group, and  also of significant prolonged latency  of  wave  I of left ear  and without correlation with thyroid stimulating hormone serum level.  Visual evoked potentials (VEP) showed a significant prolongation of P100 latency in-group of sub clinical hypothyroidism on comparison with control group. There was no correlation between the TSH serum level and evoked potential latencies (ABR and VEP)

Conclusion: The central nervous system can be early affected in sub clinical hypothyroidism and the follow up electrophysiological assessment is recommended

Keywords: subclinical hypothyroidism, Auditory brainstem evoked response (ABR), Visual evoked potential (VEP), and Electroencephalograph (EEG).

Introduction

 Thyroid disorders are the most common disorder among the endocrinal disorders that can affect the nervous system. Hypothyroidism is one of the insidious diseases, and has significant comorbidity. Subclinical hypothyroidism ((SCH) is defined when Thyroid Stimulating Hormone (TSH) exceeds the upper normal serum level with normal serum free T4 level (Silva and Costa, 2013).

The sub clinical hypothyroidism prevalence is 4-10% (Al Eidanet al., 2018). The subclinical hypothrodism commonly affecting the elderly and more among females than males (Silva and Costa, 2013). Central nervous system  is frequently affected in hypothyroidism with documentation of central delays as abnormal auditory brainstem evoked potential delayed latencies. And abnormal delayed visual evoked potentials latency and short amplitude (Gupta et al.,  2016) , and (Gupta et al., 2017).

Thyroxin deficiency affects the brain function, and the first and prominent manifestations is impairment of vision and slow thinking (Davis and Tremont, 2007)

Hearing affection iscommon  in cases of hypothyroidism, but the actual incidence is uncertain. It may affect 25% in cases of acquired and 35-50 % of cases  with congenital hypothyroidism (Kowsalya et al.,2011).

The evoked potentials is an objective and reliable measurements of the related sensory function and tracts. In addition,it is sensitive to detect silent lesion in these tracts. The Visual Evoked Potential (VEP) can assess the visual pathway up to visual cortex (Dubey et al., 2022).

Thyroid hormones have essential roles in neurotransmission,axonal transportation, and myelin formation. Thyroid hormone deficiency cause disturbance in impulse conduction and perception (Jayanthi and Vinodha, 2016).

Evoked potentials are principally appropriate for a noninvasive assessment of a numeral of afferent paths in nervous system(Dubey et al., 2022).

The furthermost prevalent disorder forgoing the manifest hypothyroidism is subclinical hypothyroidism. This can be identified when normal titraiodothyroxin (T3) and free thyroxin (T4) serum levels but thyroid stimulating hormone of high serum level. The thyroid hormonesare essential in development, growth of neurons and myelination(Jaiswal and Dhankad, 2020).

      The neurophysiological studies showed abnormal measurements in cases of   subclinical hypothyroidism, and the studies in valuation of  nervous system ( central and peripheral) in patients with sub clinical hypothyroidism is insufficient and contra- versed (Jaiswal and Dhankad,  2020).Sub clinical hypothyroidism representation is common in outpatient clinic by a symptoms like sexual dysfunction, paresthesia, chronic fatigue, myalgia, psychiatric symptoms, and mild cognitive impairment or asymptomatic (Silva and Costa, 2013).

The aim of the present study was to assess objectively the silent changes of central nervous system function  among cases of subclinical hypothyroidism.

Patients and Methods

Fifty consecutivesrecently diagnosed subclinical hypothyroid patients referred from outpatients’ clinic of Internal Medicine Department to Neurophysiology unit of Neurology Departmentof Al-Azhar University Hospitalin new Damietta, and 50age and gender matchedeuthyroid healthy persons attended to the out patients as relatives to our stuffand 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: (a) Other systemic sicknesses like: renalimpairment, diabetes, obstructive lung disease, liverimpairment, rheumatoidarthritis, dyslipidemia, malignancy, vitamin deficiency, historyofalcoholism,and manifest thyroid disease. (b) Patients with hearing problems as detected on history and examination, which interfere with auditory brain stem evoked potential (like  multiple sclerosis, cerebellopontine angle lesions, brainstem stroke, or hearing loss). (c) Patients with visual diminishing as noticed on the  history and  examination, which affect the visual evoked potential (like glaucoma, cataract, marked visual impairment, vitreous opacities,  multiple sclerosis, or any cerebral causes affecting the visual pathway).

Biochemical analysis of thyroid function included  quantity TSH, free T3, and free T4 serum level. Subclinical hypothyroidism (SCH) was demarcated when serum level of thyroid stimulating hormone (TSH) beyond the  high level  of normal even with normal serum level of free thyroxine(Silva and Costa, 2013).  The subclinical hypothyroidism was diagnosed when TSH level outdid the normal range) 0.27-4.5 uIU/ mL), and FT4 within normal range (0.93-1.7ng/dL). 

Evoked potentials (auditory and visual) Studies were piloted via Nihon Kohden machine, Model UT- 0800 J. Box BOARD (2CH) For JB-942BK, (made in Japan).  Subjects scalp were washed with soap and water on the day of the record. We placed the disc electrodes according the 10-20 standard system using adhesive  conducting paste.

Auditory brainstem evoked potentials (ABR):

 The electrodes were placed as followed: Reference electrode on vertex(Cz), the active on mastoid of each stimulated ear, and  the ground on forehead. 

The earphone stimulators: The  click stimulus at rate of 11 HZ of 90 dB intensity delivered to the stimulated ear,  and  on other non stimulated ear masking sound of 40 dB.  The  filter setting  ranged from  low cut (100 Hz) to high cut (3000 Hz). The  sweep speed: 1 ms/division, and sensitivity at 0.5 μv/division.1000 auditory responses were summated and analyzed  and displayed as ABR latencies and inter peak latencies (I,III,V,I-III,III-V, and I-V) measurements(Karl etal., 2003 , and Ali & Al-Adl, 2021).

Visual evoked potential (VEP):

 VEPs were recorded by using a pattern reversing checkerboard. The filter frequency was 1–100 Hz, analysis time 300 ms, sensitivity 20 uV/division, rate of stimulation 1 Hz and averaging 200. The electrode placements: The reference electrode on the vertex (Cz),  the active on occiput (Oz), and the ground on forehead. Stimulator:  A pattern reversing checker board presented on a monitor 1 meter from a tested eye in semi dark room at rate 1-2 Hz , the subject instructed to fix the examined eye at fixation point and cover the other eye. The visual response were summated and analyzed and displayed as P100 latency  among VEP response witch including  negative wave latencies ( N 75 and N 145) and positive wave latency (P100)(Karl et al., 2003 , and Ali & Al-Adl, 2021).

Conventional watchfulness EEGs were recorded consuming an 20-channel EEG system - Medicom MTD using scalp electrodes Placed according  to the international 10-20 system with referential  and bipolar montages.  Photic and hyperventilation stimulation were done as provoking tests.

Statistical analysis: The collected data were analyzed using the SPSS version 25. The data were expressed as means and standard deviation. Numerical data were compared by student t test for means. Pearson Correlation Coefficient test was used for study the correlation between TSH level and parameters of evoked potentials (visual and auditory) within the subclinical hypothyroidism group. P< 0.05 was considered significant.

Results

On comparison of both groups as regard of age distribution and mean serum level of  T4  no significant difference, and significant difference as regard of TSH mean serum level (Table1).

Table (1): comparison between group I(control) and group II (subclinical hypothyroidism) as regard of age, T4 and TSH serum level.

FT4:free thyroxin . TSH: thyroid-stimulating hormone

Auditory brain stem evoked potential (ABR):Latencies and inter peak latencies of both ears showed  significant prolongation  of  III&V wave latencies ,  and inter peak latencies of I-V, & III-Vamong the subclinical group on comparison with the control group, and  also of significant prolonged latency of  wave  I of left ear.(Tables2&3).

Table (2): Comparison of absolute latencies and inter‑peak latencies of  group I (control) and  group II(sub clinical hypothyroid patients) of right ear ABR

*P value<0.05. BAEP: Brainstem auditory evoked potential

Table (3): Comparison of left ear ABR absolute latencies and inter‑peak latencies of control (group I) and sub clinical hypothyroid patients (group II)

*P value<0.05.

Visual evoked potential (VEP):  There was a significant prolongation of P100 latency in group of sub clinical hypothyroidism on comparison with control group (Table4).

Table (4): Comparison of visual evoked potential (VEP) P100 latency of group I and group II

The  correlation between mean serum level of TSH and  evoked potential latencies (ABR & VEP):  There was no significant correlation between TSH  serum levels and various latencies of ABR and VEP waves (Table 5).

Table (5): correlation between TSH serum level and various latencies of evoked potentials (ABR and VEP)

Electroencephalography EEG:Eighteen patients (36%) had EEG changes. Thirteen patients (26%) had diffuse slowness of background formed mainly of theta wave activity with or without paroxysmalhigh voltage theta or delta wave activity (16%) (Table 6).

Table (6): EEG changes among patients of sub clinical hypothyroidism::

Discussion

 In our  study, ABR and VEP  results were  suggestive of central nervous system affection in cases of subclinical hypothyroidism. P100 latency showed significant prolongation on comparison with control group and withoutsignificant correlation with thyroid stimulating hormone,and this co agreed with Gupta  et al. (2016)  and Sankareswari  et al. (2016) who observed prolonged P 100 latency in patients with early stage of hypothyroidism which also reported improvement of P100 latency on treatment.Tamburini et al. (1989) noted that 3 patients of 9 recently diagnosed hypothyroid patients had aberrantly increased latencies, while 7 had a lesser than ordinary amplitude,and  attribute these changes to metabolic derangement and not to structural abnormalities,where thyroid hormones have essential role in neurotransmission, axonal transportation and myelin formation. Thyroid hormone deficiency causes disturbance in impulse conduction, and perception lack of thyroid hormones affect the mitochondrial oxidation leading to lack of ATP and lack of proteins synthesisthat causing oxidative damage of myelin sheath and oligodendroglial cells resulting demyelination and  latency prolongation of P100, and ABR wave latencies (Jayanthi & Vinodha, 2015 and  Jayanthi & Vinodha, 2016). .

Khedr  et al. (2000) also found a significant increased  P100 latency and decrease of VEP amplitudes in hypothyroid cases on comparison with the healthy group. However, there wasno correlation between these findings and thyroid stimulating and thyroid hormonal serum levels. The ABR waves have different sources, and so each wave represented activity of its generator source. Wave I signify peripheral nerve but other waves II.III.IV  and V signify cochlearnucleus,superior olivary nucleus, lateral lemniscus and inferior colliculus,correspondingly. I-III interpeak latency represent the conduction across the acoustic nerve throughsubarachnoidspace into the lower pons. I-V interpeak latency representsconduction across proximal acoustic nerve over pons to midbrain. III-V inter peak latency represent neural conduction across the lower pons to mid brain. Thus, ABR is useful for testing the hearing pathway in cases of subclinical hypothyroidism (Sharma et al., 2015)

In our study, latencies and inter peak latencies of both ears showed  significant prolongation   of  III &V wave latencies ,  and inter peak latencies of I-V, & III-V among the subclinical group on comparison with the control group, and  also of significant prolonged latency  of  wave  I of left ear  and without correlation with thyroid stimulating hormone serum level.This reach agreement with Sharma et al. (2015) where they concluded that   cases of subclinical hypothyroidism  with normal hearing showed prolonged V wave latency in ABR of both ears that mean central auditory pathway was significantly affected in subclinical hypothyroid cases.Gupta etal. (2016)reported prolonged  all ABR latencies and inter peak latencies of hypothyroid group on comparison with  control group.Ozata et al.  (1995) reported in their study no significant changes in BAEP in group of subclinical hypothyroidism on comparison with the control group.

In our study,the common EEG abnormality was diffuse slowness of background with and without  paroxysmal high voltage activity that can be interpreted  by cerebral  hypoperfusion and this co agreed with Frochetti et al. (1997) and Khedr  et al. (2000) who studied patients with rapidly progressive dementia, and using EEG and  single photon emission tomography subclinical hypothyrodism which were reversed with treatment.

Conclusion:The subclinicalhypothyroidism can affect the central nervous system sub clinically and so the electrophysiological examination must be done for all cases of subclinical hypothyroidism for early diagnosis and early treatment.

References

Al Eidan ,  Ur Rahmana S, Al Qahtani S, Al Farhan AI and Abdulmajeed I (2018): Prevalence of subclinical hypothyroidism in adult visiting primary health care setting in Riyadh, Journal of Community Hospital Internal Medicine Perspectives,8(1):11-15.

Ali HA and Al-Adl AS (2021): Electrophysiological biomarkers of central nervous system affection in cases of chronic obstructive pulmonary disease (COPD), The Egyptian Journal of Neurology, Psychiatry and Neurosurgery, 57(1):1-8

Davis JD and Tremont G (2007): Neuropsychiatric aspects of hypothyroidism and Treatment reversibility, Minerva Endocrinol,  32(1):49–65.

Dubey, N., Rai, P., Arora, J., Rai, N.and Budholia, P. K. (2022): A comparative study on visual evoked potential (VEP) wave P100 latency in hypothyroid and euthyroid individuals,  International Journal of Health Sciences, 6(S3), 3800–3810.

Forchetti CM, Katsamakis G and Garron DC (1997): Autoimmune thyroiditis and a rapidly progressive dementia: Global hypo perfusion on SPECT scanning suggests a possible mechanism. Neurology, 49:623–626.

Gupta N,Arora M, Sharma R and Arora KS (2016): Peripheral and central nervous system involvement in recently diagnosed cases of hypothyroidism: an electrophysiological study, Ann Med Health Sci Res, 6: 261-6.

Gupta S, Kaiti R, and Gupta G (2017): Evaluation of the Female Patients with Subclinical Hypothyroidism, Journal of Clinical and Diagnostic Research, 11(6): 13-16

Jaiswal D and Dhankad PR (2020): Motor nerve conduction studies in newly diagnosed subclinical hypothyroidism patients, International Journal of Science and research(INJSR) 9(7):700-703.

Jayanthi M and Vinodha R. (2015): Prolongation of VEP P100 latency in hypothyroidism. Int J Curr Res. 7:19645‑8.

Jayanthi, M and Vinodha, R.  (2016): Prolongation of interpeak latency of brainstem auditory evoked potential in hypothyroidism, Int J Med Res Health Sci., 5(3):22–27.

Karl E. Misulis and Thomas C. Head (2003): Brainstem auditory evoked potentials, Visual evoked potentials. Part II: Electroencephalography. In: Karl E. Misulis and Thomas C. Essential of clinical neurophysiology; 3rd edition. Garland Science, 191-208, 37-83.

Khedr EM, El Toonyb LF, Tarkhana MN and Abdella G (2000): Peripheral and Central Nervous System Alterations in Hypothyroidism: Electrophysiological Findings, Neuropsychobiology, 41:88–94.

Kowsalya V, Chanderasekhar and Vijavalakshmi (2011):  Electrophysiological changes on brainstem auditory evoked potentials in hypothyroid patients. Journal of Pharmacy Research, 4(8):2856-2859

Sankareswari A, Affiya Shreen L, Vigil TD, Naveen Sand Chandrasekhar M. (2016): Evaluation of peripheral nerve conduction and visual evoked potential in newly diagnosed hypothyroid females, Int J Med Res Health Sci., 5:43‑6.

Sharma K, Behera J K, Kumar N, Sood S, MadanH S and Das S., (2015) : Brainstem Evoked Potential in Newly Diagnosed Patients of Subclinical Hypothyroidism,  North American Journal of Medical Sciences, 7 (4): 131-134.

Silva GAR and Costa TB(2013):Subclinical hypothyroidism : A review for the clinic physician, Rev Bras Clin Med. São Paulo,11(3):289-95.

Tamburini G, Tacconi P, Ferrigno P, Cannas A, Massa GM, Mastinu R Velluzzi F, Loviselli A and Giagheddu M (1998): Visual evoked potentials in hypothyroidism: A long-term evaluation. Electromyogr Clin Neurophysiol,   38:201–205.

Ozata M, Ozkardes A, Corakci A and Gundogan MA. (1995): Subclinical hypothyroidism does not lead to alterations either in peripheral nerves or in brainstem auditory evoked potentials (BAEPs), Thyroid,5:201-5.

تأثر الجهاز العصبي المركزي الصامت في حالات قصور الغدة الدرقية تحت الإكلينيكي

حسام عبد المنعم علي

قسم طب المخ والاعصاب ، كلية الطب ، جامعة الأزهر ، دمياط.

خلفية البحث : يعتبر قصور الغدة الدرقية أحد أكثر اضطرابات الغدد الصماء التي يمكن أن تؤثر على الجهاز العصبي المركزي

 الهدف من البحث: تقييم التأثير الصامت للعصب المركزي بين حالات قصور الغدة الدرقية تحت الإكلينيكي.

المرضى وطرق البحث : تمت إحالة خمسين مريض من مرضى القصور السريرى للغدة الدرقية الذين تم تشخيصهم حديثًا من العيادة الخارجية لقسم الباطنية العامة إلى وحدة الفسيولوجيا العصبية فيقسم المخ والأعصاب بمستشفى الأزهر الجامعى بدمياط الجديدة , ومجموعة ضابطة من الاصحاء من نفس اعمار المرضى وكان  عددهم خمسون. وتم إجراء الدراسة الفيسيولوجية الكهربية لكلتا المجموعتين بما في ذلك تخطيط كهربية الدماغ والجهود المستحثة للعصب  السمعى البصرى لجميع المجموعات المدروسة .

نتائج البحث: بالنسبة للتخطيط الكهربائي للدماغ ، كان 36٪لديهم نشاط غير طبيعى في مخطط كهربية الدماغ: (26 ٪) عانوا من تباطؤ منتشر في نشاط الخلفية يتكون أساسًا من نشاط موجة ثيتا مع أو بدون الانتيابي

نشاط موجة ثيتا أو دلتا ذات الجهد العالي ’ 16٪. أظهرت الإمكانات السمعية المحفزة إطالة كبيرة في زمن انتقال   V فقط بين المجموعة السريرية الفرعية بالمقارنة مع المجموعة الضابطة: وقد أظهرت الإمكانات المرئية المحرضة إطالة معنوية في زمن انتقال P100 في مجموعة قصور الغدة الدرقية السريري مقارنة بمجموعة التحكم’, لم يكن هناك ارتباطا بين مستوى  الهرمون المحفز للغدة الدرقية  فى الدم وزمن الكمون للموجات  III&V وايضا الزمن البينى بين المجات   V-III & V-Iو وزمن الكمون للموجة P100 وتغييرات التخطيط الكهربى للدماغ.

الاستنتاج:  يمكن أن يتأثر الجهاز العصبي المركزي مبكرًا بقصور الغدة الدرقية السريري ويوصى بالمتابعتة  المبكرة من خلال التقييم الفسيولوجي الكهربائي  (تخطيط كهربية الدماغ والجهود المستحثة للعصب  السمعى البصرى)  .

الكلمات الدالة: قصور الغدة الدرقية تحت الإكلينيكي ، الفيسيولوجيا الكهربية ، كهربية الدماغ والجهود المستحثة للعصب  السمعى والبصرى  .