Evaluation of thyroid function tests among children with neurological disorders

Abstract

Background: Thyroid hormones (THs) are essential for brain development. Numerous studies have identified significant links between thyroid dysfunction and cognitive function. However, research on the significance and necessity of thyroid function tests in diagnosis of neurological disorders is limited and subject to controversy.

Methods: Our study employed a combination of meta-analysis and case-control design. For the meta-analysis, we conducted a systematic search of online databases for studies that compared thyroid function tests in children with neurological disorders to controls. In our case-control study, we recruited a total of 11836 children, comprising 7035 cases and 4801 healthy controls. Wilcoxon Rank Sum Test was used to determine characteristics of thyroid function between the cases and healthy controls. In order to exclude the false discovery rate (FDR), the Benjamini-Hochberg (BH) procedure is applied.

Results: A total of 12 relevant literature sources were included in the meta-analysis. Compared with controls, free thyroxine (FT4) levels were significantly decreased in neurological disorders in meta-analysis (MD = -0.29, 95% CI: -0.50 to -0.09), whereas thyroid-stimulating hormone (TSH) levels showed no significant difference (MD = -0.07, 95% CI: -0.36 to 0.21). In our case-control study, levels of free thyroxine (FT4), total triiodothyronine (TT3), total thyroxine (TT4), and anti-thyroglobulin antibodies (TG-Ab) were notably reduced among individuals with neurological disorders, compared with healthy controls (P<0.001, P<0.001, P=0.036, P=0.006). However, thyroid-stimulating hormone (TSH) levels did not show any statistically significant differences among the cases and controls.

Conclusions: Our research demonstrates that, in comparison to controls, children with neurological disorders exhibited a significant decrease in FT4 levels, while TSH levels remained unchanged. This finding provides a reference for potential serum marker of neurological disorders in children. Replication in future studies with the assessment of THs is needed to determine whether thyroid function should be included as a routine screening in these children.

Keywords: attention deficit disorder with hyperactivity; autism spectrum disorder; children; neurological disorders; thyroid function tests.

Figure 1

Meta-Analysis Diagram of Included Studies. Figure 1 illustrates the process of the meta-analyses. We searched PubMed, Embase, Cochrane Library, and Web of Science for relevant literature. A total of 1,267 articles were retrieved, and after removing duplicates, 774 articles remained. After reviewing the titles and abstracts, 45 full-text articles were examined, and finally, 12 articles were included.

Figure 2

Meta-Analysis of FT4 levels in Children with Neurological Disorders compared to Healthy Controls. A total of 9 studies of FT4 comprising 837 cases and 8664 controls were included in the final meta-analysis. The heterogeneity was low (P=0.41>0.05, I²=4%<50%), so a common-effects model was used. Compared to the controls, the FT4 levels in the cases were significantly lower, with statistical significance (MD = -0.29, 95% CI: -0.50 to -0.09).

Figure 3

Meta-Analysis Comparing TSH Levels in Children with Neurological Disorders and Healthy Controls. 14 studies of TSH, involving 1191 cases and 8933 controls, were included in the final meta-analysis. Given the low heterogeneity (P<0.01, I²=81%>50%), a random-effects model was applied. When compared to the controls, there was no statistically significant difference in TSH levels in the cases (MD = -0.07, 95% CI: -0.36 to 0.21).

Figure 4

Sensitivity Analysis of FT4 Levels in Children with Neurological Disorders Compared to Healthy Controls. In the sensitivity analysis of the meta-analysis, the estimates from the 9 studies on FT4 levels remained within the 95% confidence intervals throughout all iterations.

Figure 5

Sensitivity Analysis of TSH Levels in Children with Neurological Disorders Compared to Healthy Controls. The estimates from the 14 studies, in the sensitivity analysis of the meta-analysis, on TSH levels remained within the 95% confidence intervals throughout all iterations.

Figure 6

Receiver Operating Characteristic (ROC) Analysis in FT4 between the Cases and the Controls. Following the implementation of a random forest model, the Area Under the Curve (AUC) was 0.76 and the 95% confidence interval for the AUC ranged from 0.75 to 0.77.