Thyroid disorders, thyroid autoimmunity, and anxiety—a systematic review and meta-analysis of population-based studies

Abstract

Objectives Previous studies, largely based on case–control samples, have suggested that hypothyroidism, hyperthyroidism, and thyroid autoimmunity may be associated with an increased risk of anxiety. However, whether a true association exists remains unclear, as population-based studies, which draw on more representative samples and are therefore less prone to selection bias, have yielded conflicting results. This study aimed to investigate the association between thyroid dysfunction and anxiety disorders in population-based cohort and cross-sectional studies. Methods We conducted a systematic literature search in PubMed, PsycINFO, and Embase databases from inception to March 2026. Two reviewers independently selected population-based cohort and cross-sectional studies reporting laboratory- or International Classification of Diseases (ICD)-based diagnoses of thyroid dysfunction or autoimmunity, and anxiety outcomes according to validated criteria or rating scales. Study quality was assessed using the Newcastle-Ottawa Scale. All meta-analyses were conducted using random-effects models, and heterogeneity was quantified using the I 2 statistic (pre-registration in Prospero: CRD42020164791) Results Out of 2,548 screened articles, 12 studies comprising 676,658 participants were included. Six studies dealt with hypothyroidism, seven with hyperthyroidism, and four with autoimmunity. Meta-analyses revealed small and mostly statistically non-significant positive summary estimates for hypothyroidism (OR 1.13, 95% CI [0.77–1.65]; I 2 = 86%), hyperthyroidism (OR 1.38, 95% CI [1.03–1.83]; I 2 = 86%), and thyroid peroxidase antibody (TPOAb) (OR 1.47, 95% CI [0.73–2.94]; I 2 = 65%). Sensitivity and subgroup analyses, as well as studies summarized qualitatively, showed patterns consistent with the main results. Limitations The number of studies is small, and thyroid pathology as well as anxiety are heterogeneously defined. Conclusion The evidence is inconclusive: Small positive associations seem likely, but confidence intervals are also in agreement with intermediate positive and even small protective effects, suggesting either limited data or the absence of relevant associations between thyroid pathology and anxiety. Further population-based studies based on established diagnostic criteria are warranted.