J Am Acad Orthop Surg. 2026 Mar 15;34(6):e841-e849. doi: 10.5435/JAAOS-D-25-00325. Epub 2025 Sep 4.
ABSTRACT
OBJECTIVES: There is a burgeoning body of research suggesting a possible relationship between thyroid function and carpal tunnel syndrome (CTS). This study aimed to investigate the potential causal relationship between various aspects of thyroid function and CTS using a two-sample mendelian randomization (MR) approach. However, their causal relationship has yet to be conclusively determined.
METHODS: Using summary data from extensive genome-wide association studies, we conducted a two-sample MR analysis to investigate the potential genetic causal relationship between thyroid function-encompassing hyperthyroidism, hypothyroidism, thyroid-stimulating hormone, free thyroxine (FT4), free triiodothyronine, total triiodothyronine, and their ratios (free triiodothyronine/FT4 and total triiodothyronine/FT4)-and CTS. Our analytical strategy included the inverse-variance weighted (IVW) method, supplemented by MR-Egger regression, weighted median, and weighted mode analyses, with the IVW method regarded the primary analytical approach. Sensitivity analyses were done using Cochran Q test, the MR pleiotropy residual sum and outlier test, MR-Egger regression, and the leave-one-out method.
RESULTS: Robust sets of genetic instrumental variables were identified for different aspects of thyroid function using stringent selection criteria (including F-statistics >10). The IVW method, relying on genome-wide association studies summary data for thyroid function, did not provide evidence a supporting causal effect of genetically predicted thyroid function on CTS (all P > 0.05). Despite observed heterogeneity and pleiotropy in some relationships, the overall findings were consistent and robust across all sensitivity analyses.
CONCLUSION: Our two-sample MR analysis did not establish a potential causal relationship between thyroid function and CTS, highlighting the necessity for further studies to clarify the complex interplay between these two entities.
PMID:41793772 | DOI:10.5435/JAAOS-D-25-00325
