Elevated Thyroid Autoantibodies and Intracranial Stenosis in Stroke at an Early Age

Abstract

Background

Previous studies have shown that hyperthyroidism was related to Moyamoya disease and intracranial artery stenosis. However, it is not clear whether thyroid hormone or thyroid autoantibodies was associated with them.

Aims and/or hypothesis

Thyroid autoimmunity was previously shown to be associated with Moyamoya disease. Our study aimed to investigate the association between thyroid autoantibodies and intracranial large artery stenosis in young ischemic stroke patients with apparent euthyroid states.

Methods

We retrospectively reviewed first-onset ischemic stroke patients (age ≤55 years old) consecutively admitted to a single academic center. Intracranial large artery stenosis was defined as ≤50% luminal diameter narrowing. We compared demographic profiles, risk factors (age, hypertension, diabetes, current smoker, atrial fibrillation, hyperlipidemia), thyroid function test, and thyroid autoantibodies including antithyroperoxidase antibody and antithyroglobulin antibody between patients with and without intracranial large artery stenosis. We also performed multivariate logistic regression analysis to evaluate the association between thyroid autoantibodies and intracranial large artery stenosis.

Results

A total of 351 patients were analyzed. The mean age of the patients was 47·0 ±7·7 (range, 10–55 years), and 252 (71·8%) patients were male. We identified intracranial large artery stenosis in 121 (34·5%) patients. Patients with intracranial large artery stenosis showed a higher frequency of elevated antithyroperpxidase antibody levels in comparison with nonintracranial large artery stenosis group (16·5% vs. 3·9%, P < 0·001). After adjusting for covariates, the presence of elevated antithyroperpxidase antibody levels (odds ratio: 5·318; 95% confidence interval: 2·157–13·110, P <0·001), age (odds ratio: 1·037; 95% confidence interval: 1·002–1·073, P = 0·039), and atrial fibrillation (odds ratio: 0·091; 95% confidence interval: 0·011–0·756, P = 0·027) was independently associated with intracranial large artery stenosis.

Conclusions

Thyroid autoantibodies may be associated with the presence of intracranial large artery stenosis in young stroke patients, potentially providing insight on immune pathogenesis of intracranial large artery stenosis.

Keywords

age antithyroperoxidase antibody stenosis stroke thyroid

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References

Scott

Smith

. Moyamoya disease and moyamoya syndrome. N Engl J Med 2009; 360: 1226–37.

Zhang

Dong

. Increased thyroid function and elevated thyroid autoantibodies in pediatric patients with moyamoya disease. Stroke 2011; 42: 1138–9.

Kim

Heo

Shin

. Association of thyroid autoantibodies with moyamoya-type cerebrovascular disease: A prospective study. Stroke 2009; 41: 173–6.

Zhang

Chen

Shi

. Correlation between thyroid autoantibodies and intracranial arterial stenosis in stroke patients with hyperthyroidism. J Neurol Sci 2012; 318: 82–4.

Chimowitz

Kokkinos

Strong

. The warfarin-aspirin symptomatic intracranial disease study. Neurology 1995; 45: 1488–93.

Burke

Sherma

. Moyamoya disease: A summary. Neurosurg Focus. 2009; 26: E11.

You

McNeil

O'Malley

. Risk factors for stroke due to cerebral infarction in young adults. Stroke 1997; 28: 1913–8.

Gao

Wang

. Chinese ischemic stroke subclassification. Front Neurol 2011; 2: 6–11.

Kabelitz

Liesenkotter

Stach

. The prevalence of antithyroid peroxidase antibodies and autoimmune thyroiditis in children and adolescents in an iodine replete area. Eur J Endocrinol 2003; 148: 301–7.

10.

Hollowell

Staehling

Flanders

. Serum TSH, t4, and thyroid antibodies in the United States population (1988 to 1994): National Health and Nutrition Examination Survey (NHANES iii). J Clin Endocrinol Metab 2002; 87: 489–99.

11.

Kasagi

Takahashi

Inoue

. Thyroid function in Japanese adults as assessed by a general health checkup system in relation with thyroid-related antibodies and other clinical parameters. Thyroid 2009; 19: 937–44.

12.

Teng

Shan

. Antithyroperoxidase and antithyroglobulin antibodies in a five-year follow-up survey of populations with different iodine intakes. J Clin Endocrinol Metab 2008; 93: 1751–7.

13.

Bandaru

Boddu

Laxmi

. Seroprevalence of Chlamydia Pneumoniae antibodies in stroke in young. Can J Neurol 2009; 36: 725–30.

14.

Knoflach

Kiechl

Kind

. Cardiovascular risk factors and atherosclerosis in young males. ARMY study (atherosclerosis risk-factors in male youngsters). Circulation 2003; 108: 1064–9.

15.

Garlichs

Cicha

Raaz

. CD40/CD154 system and pro-inflammatory cytokines in young healthy male smokers without additional risk factors for atherosclerosis. Inflamm 2009; 58: 306–11.

16.

Utku

Asil

Celik

Tucer

. Reversible MR angiographic findings in a patient with autoimmune Graves Disease. AJNR Am J Neuroradiol 2004; 25: 1541–43.

17.

Malik

Russman

Katramados

. Moyamoya syndrome associated with Graves' Disease: A case report and review of the literature. J Stroke Cerebrovasc Dis 2011; 20: 528–36.

18.

Xiang

Zhao

. Impairment of endotheliumdependent arterial dilation in Hashimoto's thyroiditis patients with euthyroidism. Clin Endocrinol (Oxf) 2006; 64: 698–702.

19.

McLachlan

Rapoport

. Why measure thyroglobulin autoantibodies rather than thyroid peroxidase autoantibodies? Thyroid 2004; 14: 510–20.

20.

Laurat

Poirier

Tupin

. In vivo downregulation of T helper cell 1 immune responses reduces atherogenesis in apolipoprotein e-knockout mice. Circulation 2001; 104: 197–202.

21.

Karanikas

Schuetz

Wahl

. Relation of anti-TPO autoantibody titre and T-lymphocyte cytokine production patterns in Hashimoto's thyroiditis. Clin Endocrinol 2005; 63: 191–6.

22.

Haraba

Antohe

. T cells are active participants in the progression of atherosclerotic plaques. Dig J 2011; 6: 1529–34.

23.

Franklin

Gustin

Wong

. Hemodynamic patterns of age-related changes in blood pressure. Circulation 1997; 96: 308–15.

24.

Zhang

Wang

. Arterial stiffness and asymptomatic intracranial large arterial stenosis and calcification in hypertensive Chinese. Am J Hypertens 2011; 24: 304–9.

25.

National Collaborating Centre for Chronic Conditions (UK). Type 2 Diabetes: National Clinical Guideline for Management in Primary and Secondary Care (Update). London: Royal College of Physicians (UK); 2008. (NICE Clinical Guidelines, No. 66.) Available at http://www.ncbi.nlm.nih.gov/books/NBK53885/ (accessed 13 August 2013).

26.

Albucher

Ferrieres

Ruidavets

. Serum lipids in young patients with ischaemic stroke: A case-control study. J Neurol Neurosurg Psychiatry 2000; 69: 29–33.

27.

Tan

Venketasubramanian

Saw

. Hyperhomocystinemia and risk of ischemic stroke among young Asian adults. Stroke 2002; 33: 1956–62.

28.

Money

Muss

Thelmo

. Immunocytochemical localization of estrogen and progesterone receptors in human thyroid. Surgery 1989; 106: 975–8.

29.

Kim

Cha

Kim

. Increases in cerebral atherosclerosis according to chads2 scores in patients with stroke with nonvalvular atrial fibrillation. Stroke 2011; 42: 930–4.