Increased Thyroid Function and Elevated Thyroid Autoantibodies in Pediatric Patients With Moyamoya Disease
A Case-Control Study
Background and Purpose—The purpose of this study was to investigate whether thyroid function and thyroid autoantibodies were associated with the risk of moyamoya disease in pediatric subjects.
Methods—Thyroid function and thyroid autoantibodies were evaluated in patients with moyamoya disease and control subjects, and their associations with moyamoya disease were estimated using multivariate analysis.
Results—We included 114 pediatric patients and 114 healthy control subjects. The patients displayed higher prevalence of increased thyroid function and elevated thyroid autoantibodies in comparison with control subjects. These remained significant after multivariate adjustment; the ORs (95% CI) for increased thyroid function and evaluated thyroid autoantibodies were evaluated as 12.47 (1.55 to 100.51) and 4.33 (1.29 to 14.59), respectively.
Conclusions—Increased thyroid function and elevated thyroid autoantibodies are associated with moyamoya disease and therefore monitoring of thyroid function and thyroid autoantibodies in patients with moyamoya disease is suggested, which might help to guide subsequent clinical management.
Moyamoya disease (MMD) as well as several other cerebrovascular diseases has been demonstrated for their associations with thyroid disease.1,–,3 Recently a high prevalence of thyroid autoantibodies was observed in patients with adult-type MMD,4 indicating the potential role of thyroid autoantibodies in adult-type MMD, which role, however, remains largely unknown in pediatric MMD. Using a case–control design, we investigated the contribution of abnormal thyroid function and thyroid autoantibodies to the risk of MMD in Chinese pediatric subjects.
Materials and Methods
We prospectively recruited pediatric patients (<16 years) with MMD at the Department of Neurosurgery, 307 Hospital, from May 2007 to June 2010. Age-matched healthy individuals confirmed by physical examination were selected as control subjects. Patients' inclusion and exclusion criteria are provided in the online supplement (http://stroke.ahajournals.org).
Routine clinical and laboratory tests were performed in all subjects with additional details in the online supplement. Briefly, free-triiodothyronine, free-thyroxine, thyroid-stimulating hormone, antithyroperoxidase, and antithyroglobulin were measured by ADVIA Centaur (Siemens Healthcare Diagnostics).
All subjects were grouped into 3 grades: increased thyroid function (overt and subclinical hyperthyroidism), decreased thyroid function (overt and subclinical hypothyroidism), and euthyroidism according to the criteria in the online supplement. Elevated thyroid autoantibodies were determined as either antithyroperoxidase or antithyroglobulin >60 U/mL in accordance with the manufacturer's reference.
Data were analyzed using SPSS 15.0. Continuous data were compared by paired t test or Wilcoxon test where appropriate, whereas categorical data were compared by McNemar test. The effects of increased thyroid function and elevated thyroid autoantibodies on MMD risk were estimated by forward stepwise conditional logistic regression analysis in Model A and Model B, respectively. Any variable with a probability value <0.15 in univariate analysis was considered for inclusion in the multivariate model.
We included 114 patients with MMD and 114 healthy control subjects. Clinical and laboratory characteristics are presented in the Table and Supplemental Table 1. In comparison with control subjects, patients with MMD demonstrated with higher levels of total cholesterol, homocysteine, and family history of cerebrovascular disease (P<0.5 for all). Increased thyroid function and elevated thyroid autoantibodies were observed more frequently in patients than in control subjects (10.5% versus 0.9%, P=0.003; 13.2% versus 3.5%, P=0.019, respectively).
In Model A in which thyroid function was evaluated, we observed a significant association between increased thyroid function and higher risk of MMD (OR, 12.47; 95% CI, 1.55 to 100.51; P=0.018) after adjustment for covariables, including total cholesterol, triglyceride, homocysteine, glucose, creatinine, white blood cell count, and family history of cerebrovascular disease, although in Model B in which thyroid autoantibodies were included, elevated thyroid autoantibodies were significantly correlated with an increased risk of MMD (OR, 4.33; 95% CI, 1.29 to 14.59; P=0.018). All variables finally included in the models are given in Supplemental Table II.
In the present study, we demonstrated that the risk of MMD was substantially augmented for increased thyroid function and elevated thyroid autoantibodies with statistical significance. To our knowledge, this is the first study to describe the prevalence of thyroid function abnormalities and thyroid autoantibodies in a large population of pediatric patients with MMD. It is worth noting that the significantly higher prevalence of overt plus subclinical hyperthyroidism in the patients with MMD than in control subjects provided strong evidence that thyroid function abnormalities might play roles in MMD development.
The study design does not allow elucidation of the mechanism whereby thyroid function and thyroid autoantibodies are associated with MMD. Previous studies used to suggest several arguments for the association between thyroid disease and MMD.1,2 First, excessive thyroid hormones are thought to augment cerebral metabolism and oxygen consumption and be harmful to arterial walls.5 Second, sympathic nervous activity could be enhanced in thyrotoxicosis and thereby may contribute to the stenosis of cerebral arteries.5,6 Finally, T-cell dysfunction related to immunologic stimulation of the thyroid in thyroid disease may be involved in cellular proliferation and vascular dysregulation.1,7
Several limitations should be addressed. First, selection bias cannot be completely excluded when our patients came from all over the country, whereas the majority of control subjects resided locally. However, the prevalence of overt plus subclinical hyperthyroidism in our control subjects is comparable with that reported by Teng et al,8 which provided partial evidence that our control subjects might be well representative of the general population. Second, due to the incapability of following up these patients, the clinical significance of increased thyroid function and elevated thyroid autoantibodies remains unknown in the current stage.
Based on the results from the present study, monitoring of thyroid function and thyroid autoantibodies in patients with MMD is suggested, which might help to guide subsequent clinical management.
Sources of Funding
This study was supported by grants from the National Science Fund for Distinguished Young Scholars (30725032) and the Capital Medical Science Development (ZD199908).
The online-only Data Supplement is available at http://stroke.ahajournals.org/cgi/content/full/STROKEAHA.110.608471/DC1.
- Received November 11, 2010.
- Accepted November 23, 2010.
- © 2011 American Heart Association, Inc.
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- Gerdes VE,
- Brandjes DP,
- Buller HR,
- Stam J
- Kim SJ,
- Heo KG,
- Shin HY,
- Bang OY,
- Kim GM,
- Chung CS,
- Kim KH,
- Jeon P,
- Kim JS,
- Hong SC,
- Lee KH