Causal role of thyroid function in functional outcome after ischemic stroke: A Mendelian randomization study

Background

Previous observational studies have suggested that thyroid function may be associated with functional outcome after ischemic stroke (IS). Nevertheless, the causal relationship remains unclear. This study aimed to explore the causal effect of thyroid function [thyroid-stimulating hormone (TSH), free thyroxine (FT4), hyperthyroidism, and hypothyroidism] on functional outcome (based on the modified Rankin scale) after IS by two-sample Mendelian randomization (MR) analysis.

Methods

Inverse variance weighted (IVW) was the primary method for evaluating causal associations. In addition, six additional MR methods (MR-Egger regression, weighted median, maximum likelihood, simple mode, weighted mode, and MR-PRESSO) were employed to supplement IVW. Furthermore, various sensitivity tests were conducted to assess the reliability: (i) Cochrane's Q test for assessing heterogeneity; (ii) MR-Egger intercept test and MR-PRESSO global test for evaluating horizontal pleiotropy; (iii) leave-one-out sensitivity test for determining stability.

Results

The results of IVW indicated that elevated TSH levels significantly improved functional outcome after IS (OR = 0.74, 95 % CI: 0.57-0.97, P = 0.028). In addition, six additional MR methods suggested parallel results. However, no causal effect of FT4, hyperthyroidism, and hypothyroidism on functional outcome after IS was identified. In addition, sensitivity tests demonstrated the reliability of the MR analyses, suggesting that the MR analysis was not influenced by significant heterogeneity and horizontal pleiotropy.

Conclusions

Our MR study supported that elevated TSH levels might improve functional outcome after IS. Therefore, regular monitoring and maintenance of stable TSH levels may benefit patients recovering from IS.