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Table of Contents
ORIGINAL ARTICLE
Year : 2021  |  Volume : 9  |  Issue : 1  |  Page : 14-18

Prognostic significance of thyroid dysfunction in acute stroke


1 Department of General Medicine, Kasturba Medical College, Manipal Academy of Higher Education, Manipal, Karnataka, India
2 Department of Physiotherapy, Kasturba Medical College, Manipal Academy of Higher Education, Mangalore, Karnataka, India

Date of Submission10-Mar-2020
Date of Decision11-Apr-2020
Date of Acceptance24-May-2020
Date of Web Publication03-Feb-2021

Correspondence Address:
Dr. Shivashankara Kaniyoor Nagri
Department of General Medicine, Kasturba Medical College, Manipal Academy of Higher Education, Manipal - 576 104, Karnataka
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/AJIM.AJIM_15_20

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  Abstract 


Background: Cerebrovascular accidents (CVAs) are the leading cause of morbidity and mortality. Several comorbidities have been associated with increased mortality in acute stroke patients. Conditions such as hypertension, dyslipidemia, diabetes mellitus, and thyroid dysfunction are identified as risk factors in the etiology of stroke. Methods: This is a prospective study involving 40 patients admitted with acute stroke between October 2010 and July 2012 in Kasturba Hospital, Manipal, under the Departments of Medicine and Neurology. Results: Thyroid dysfunction has been associated with CVAs and is an area of active research in the present times. Conclusion: Low T3 level was associated with unfavorable outcome and with posterior circulation stroke as accessed using the National Institutes of Health Stroke Scale.

Keywords: Cerebrovascular accident, hypertension, stroke, thyroid dysfunction


How to cite this article:
Nagri SK, Kudru CU, Amaravadi SK, Prasad L. Prognostic significance of thyroid dysfunction in acute stroke. APIK J Int Med 2021;9:14-8

How to cite this URL:
Nagri SK, Kudru CU, Amaravadi SK, Prasad L. Prognostic significance of thyroid dysfunction in acute stroke. APIK J Int Med [serial online] 2021 [cited 2021 May 14];9:14-8. Available from: https://www.ajim.in/text.asp?2021/9/1/14/308646




  Introduction Top


In acute stroke, several factors such as C-reactive protein, glucose levels on admission, fibrinogen concentration, erythrocyte sedimentation rate, and leukocyte count have been examined as prognostic factors for stroke outcome and have been found to be associated with increased morbidity and mortality.[1],[2],[3] Similarly, thyroid hormones also vary in the serum of patients with acute stroke. Thus far, there were three studies that have been published to address the importance of serum thyroid hormone levels after acute stroke. Hama et al. from Japan reported malnutrition and nonthyroidal illness syndrome after stroke in 2005;[4] another one by Alevizaki et al. described that a low T3 level is associated with the outcome in acute stroke patients from Greece in 2007;[5] the third one was done by Zhang and Meyer from New York in 2010.[6]

Critical illness is often associated with alterations in thyroid hormone concentrations in patients with no previous intrinsic thyroid disease.[7],[8],[9] This is known as nonthyroidal illness syndrome (NTIS or euthyroid sick syndrome or “low-T3 syndrome”). The most common hormone pattern in NTIS is a decrease in T3 level with normal levels of thyroxine (T4) and thyroid-stimulating hormone (TSH).[10],[11] The alterations in the thyroid hormones can be due to euthyroid sick syndrome as cited above or can be due to disturbance in hypothalamic–pituitary–thyroid axis.[6]

The objective of this prospective study is to investigate (1) possible associations of thyroid hormone status with clinical severity using the National Institutes of Health Stroke Scale (NIHSS) and outcome in the patients admitted for acute stroke and (2) whether there is association between the pituitary axis abnormality and the anterior or posterior circulation involvement.


  Methods Top


This is a prospective study involving 40 patients admitted with acute stroke between October 2010 and July 2012 in Kasturba Hospital, Manipal, under the Departments of Medicine and Neurology.

Inclusion criteria

  1. Patients aged above 18 years
  2. All acute stroke patients who present within 48 h of onset
  3. Patients without previous thyroid dysfunction
  4. Patients on hospital stay of at least 1 week.


Exclusion criteria

  1. Patients with hepatic and renal impairment at presentation
  2. Patients with sepsis
  3. Patients with Transient ischemic attacks
  4. Patients on medication that can alter thyroid function.


Basic and clinical characteristics including demographic data such as sex, age, cigarette smoking, concurrent illness, medications, and whether the stroke involves the anterior or posterior circulation from brain imaging were collected and categorized. We divided all patients into two groups with one low-T3 group and other normal-T3 group based on initial thyroid functions. Thyroid function was evaluated by measuring serum total T3, T4, and TSH within 48 h of onset of stroke. T3, T4, and TSH were measured by chemiluminescence. Normal range in our laboratory for T3 is 0.8–2 ng/mL; normal range for T4 is 5.56–12.2 mcg/dL; normal range for TSH is 0.7–7 μIU/mL. The severity of stroke was assessed using NIHSS; the severity distribution of NIHSS scores on admission was divided into three categories, mild: NIHSS <8; moderate: NIHSS 8–14; and severe: =14. Neurological impairment and improvement were assessed using the NIHSS at admission and after 1 week. Statistical analysis was performed to compare the patients with normal T3 levels and low T3 levels. Independent sample t-test (for continuous variables), Chi-square test (for categorical variables), and correlative analysis were used to determine the significance. Differences were considered statistically significant at P < 0.05. The Statistical Package for the Social Sciences (SPSS version 16, IBM Company, Chicago, Illinois) was used for analysis.


  Results Top


A total number of 40 patients who met all the above-mentioned inclusion criteria were taken into study. It included a total of 27 males and 13 females with a mean age of 55.7 years [Figure 1]. Of the total 40 strokes, 37 were ischemic and 3 were hemorrhagic. Of 40 patients, 23 were smokers, 10 were alcoholics, 26 were hypertensives, 11 were diabetics, 12 had dyslipidemia, and 6 had ischemic heart disease. Ten patients (25%) had low T3 level (<0.8 ng/ml) while 30 patients (75%) had normal T3 levels. There was no significant difference between the low-T3 and normal-T3 group in the above traits. Patients with low T3 levels had significantly high mean and median NIHSS score compared to those with normal T3 values (P = 0.02) [Figure 2]. The distribution pattern showed that much higher portion of the patients in low-T3 group belonged to moderate-to-severe category (NIHSS 8–14 or > 14) while majority of the patients in normal-T3 group fell into mild category [Table 1] and [Table 2]. There was significant difference between the normal-T3 group and low-T3 group in terms of territory of stroke [Table 3]. Majority of the patients in low-T3 group belong to posterior circulation stroke (P = 0.007) [Figure 3]. There was a significant negative correlation between T3 levels and NIHSS scores, which implied that, after acute stroke, the lower the T3 values were worse was the neurological impairment (P = 0.001) [Figure 4]. There was no significant difference about the improvement of neurological function between low-T3 group and normal-T3 group (after 1 week) (P = 0.3) [Table 4]. Two patients had low T4 out of which one patient had severe form of euthyroid sick syndrome, with all the three hormones being low. The other patient showed improvement during hospital stay and was discharged. The patient with severe form of euthyroid sick syndrome had an NIHSS score of 34. He was in persistent vegetative state and was discharged at request.
Figure 1: Sex distribution

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Figure 2: Distribution of stroke

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Figure 3: Territory of stroke

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Figure 4: Scatter plot distribution

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Table 1: NIHS score

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Table 2: Distribution of NIH score

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Table 3: Levels of T3 with Territory Of Stroke

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Table 4: Change in NIHS Score

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  Discussion Top


This short-term, prospective study showed the association of low T3, with severity of stroke and its outcome. This is the second study that used NIHSS scale to assess the stroke severity and prognosis; the other was done by Zhang and Meyer.[6] The previous study was a retrospective study done from the data available from Kaleida Health InfoClique Electronic Record System, whereas the present study was a prospective study on the patients who were admitted in the hospital. The present study included hemorrhagic strokes, while the above-mentioned study was only done on ischemic stroke. The above-mentioned study showed a significantly high NIHSS score in patients in low-T3 group and also worse prognosis in patients in low -3 group.

The present study showed a significantly high NIHSS in low-T3 group but failed to show significant difference in outcome between low-T3 and normal-T3 groups. This difference of finding can be explained by the time of reassessment. In the present study, patients were reassessed after 1 week, whereas in the previous study, data were obtained from the first clinical follow-up, i.e., after 2–4 weeks. The previous study concluded that alteration in the T3 levels did not relate to the region of stroke, suggesting that alteration of thyroid hormones is more related to metabolism rather than blood supply. In contrast, the present study showed a significant difference in the territory of stroke in the low-T3 and normal-T3 groups; in that, most of the patients with low T3 are in the posterior circulation stroke group. There was no scientific explanation for this observation, but it may suggest the role of involvement of hypothalamic–pituitary–thyroid axis.

A similar study was done by Alevizaki et al. from Greece in 2007.[5] They studied the association of low T3 levels with outcome in acute stroke patients using Scandinavian stroke scale. It too was a prospective study involving 737 patients who were followed up for 1 year. This study concluded that low-T3 syndrome was an independent predictor of early and late survival in patients with acute stroke. The similarity of this study with the present study was that it also included patients with hemorrhagic stroke. The relationship of low T3 and territory of stroke was not studied.

Another study was done by Hama et al. from Japan in 2005.[4] They reported malnutrition and nonthyroidal illness after stroke. This was a different study which concluded that nonthyroidal illness was common after stroke and was provoked by protein-energy malnutrition. Like in other systemic severe illness, a reduction of serum T3 without elevation of TSH appears to be associated with the severity of stroke and worse clinical outcome.[4],[5] Possible mechanisms include, but not limited to, the following:

Peripheral thyroid hormone metabolism changes due to alterations in the activity of the enzymes responsible for peripheral conversion of T4 to T3.[12],[13] Proinflammatory cytokine action involvement,[14] A disturbed shift in the distribution of thyroid hormones or an alteration in binding proteins,[15],[16] Excessive glucocorticoids releases in severe illness which produce inhibition of activities from hypothalamic–pituitary–thyroid axis and the conversion of T4 to T3.[17]

It has been generally accepted that low T3 accompanying severe illness is considered as an adoptive response to stress to spare energy.[5] Whether to treat or not to treat with thyroxin replacement is controversial,[10] while true hypothyroidismhas been interestingly reported that a preexisting conditionmay actually be protective in acute stroke.[11] There were no conclusive studies whether treatment of low T3 is beneficial in stroke patients. There were contradictory studies regarding the same issue. Some studies reported advantage of brain “being preconditioned” with hypothyroidism when a stroke occurs,[18] whereas one animal study showed a neuroprotective effect defined by reduction of infarct size and improvement of neurological deficit with administration of T3.[19] Further studies were required to conclude this aspect.


  Conclusions Top


  • Patients of acute stroke who present with severe neurological impairment tend to have low T3 levels in their blood
  • Alteration in T3 levels appeared to be related to the territory of stroke. Patients with posterior circulation stroke tend to have low T3 values
  • Neurological improvement is better in patients with normal T3 levels compared to patients with low T3 levels but was not statistically significant in this study.


Limitations in the present study include small sample size, single baseline measurement of the thyroid function, lack of long-term follow-up, and estimation of total T3 and T4, instead of free T3 and free T4.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
  References Top

1.
Capes SE, Hunt D, Malmberg K, Pathak P, Gerstein HC. Stress hyperglycemia and prognosis of stroke in nondiabetic and diabetic patients: A systematic overview. Stroke 2001;32:2426-32.  Back to cited text no. 1
    
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Rundek T, Sacco RL. Outcome following stroke. In Stroke: Pathophysiology, diagnosis, and management. Elsevier Inc.; 2004. p. 35-57.  Back to cited text no. 3
    
4.
Hama S, Kitaoka T, Shigenobu M, Watanabe A, Imura I, Seno H, et al. Malnutrition and nonthyroidal illness syndrome after stroke. Metabolism 2005;54:699-704.  Back to cited text no. 4
    
5.
Alevizaki M, Synetou M, Xynos K, Pappa T, Vemmos KN. Low triiodothyronine: A strong predictor of outcome in acute stroke patients. Eur J Clin Invest 2007;37:651-7.  Back to cited text no. 5
    
6.
Zhang Y, Meyer MA. Clinical analysis on alteration of thyroid hormones in the serum of patients with acute ischemic stroke. Stroke Res Treat 2010;2010:290678.  Back to cited text no. 6
    
7.
Farwell AP. Sick euthyroid syndrome in the intensive care unit. In: Irwin and Rippe's Intensive Care Medicine. Philadelphia, PA: Lippincott Williams & Wilkins; 2003. p. 1205-16.  Back to cited text no. 7
    
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DeGroot LJ. Non-thyroidal illness syndrome is functional central hypothyroidism, and if severe, hormone replacement is appropriate in light of present knowledge. J Endocrinol Invest 2003;26:1163-70.  Back to cited text no. 8
    
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Adler SM, Wartofsky L. The nonthyroidal illness syndrome. Endocrinol Metab Clin N Am 2007;36:657-72.  Back to cited text no. 9
    
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De Groot LJ. Dangerous dogmas in medicine: The nonthyroidal illness syndrome. J Clin Endocrinol Metab 1999;84:151-64.  Back to cited text no. 10
    
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Jameson JL, Weetman AP. Disorders of the thyroid gland. Harrisons principles of internal medicine. 2001;2:2060-83.  Back to cited text no. 11
    
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Bianco AC, Salvatore D, Gereben B, Berry MJ, Larsen PR. Biochemistry, cellular and molecular biology, and physiological roles of the iodothyronine selenodeiodinases. Endocr Rev 2002;23:38-89.  Back to cited text no. 12
    
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Peeters RP, Wouters PJ, Kaptein E, van Toor H, Visser TJ, Van den Berghe G. Reduced activation and increased inactivation of thyroid hormone in tissues of critically ill patients. J Clin Endocrinol Metab 2003;88:3202-11.  Back to cited text no. 13
    
14.
McIver B, Gorman CA. Euthyroid sick syndrome: An overview. Thyroid 1997;7:125-32.  Back to cited text no. 14
    
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Boelen A, Schiphorst MC, Wiersinga WM. Association between serum interleukin-6 and serum 3,5,3'-triiodothyronine in nonthyroidal illness. J Clin Endocrinol Metab 1993;77:1695-9.  Back to cited text no. 15
    
16.
Nagaya T, Fujieda M, Otsuka G, Yang JP, Okamoto T, Seo H. A potential role of activated NF-κB in the pathogenesis of euthyroid sick syndrome. J Clin Invest 2000;106:393-402.  Back to cited text no. 16
    
17.
Faber J, Kirkegaard C, Rasmussen B, Westh H, Busch-Sørensen M, Jensen IW. Pituitary-thyroid axis in critical illness. J Clin Endocrinol Metab 1987;65:315-20.  Back to cited text no. 17
    
18.
Baek JH, Chung PW, Kim YB, Moon HS, Suh BC, Jin DK, et al. Favorable influence of subclinical hypothyroidism on the functional outcomes in stroke patients. Endocr J 2010;57:23-9.  Back to cited text no. 18
    
19.
Hiroi Y, Kim HH, Ying H, Furuya F, Huang Z, Simoncini T, et al. Rapid nongenomic actions of thyroid hormone. Proc Natl Acad Sci U S A 2006;103:14104-9.  Back to cited text no. 19
    


    Figures

  [Figure 1], [Figure 2], [Figure 3], [Figure 4]
 
 
    Tables

  [Table 1], [Table 2], [Table 3], [Table 4]



 

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