What is the impact of stress on the onset and anti-thyroid drug therapy in patients with graves’ disease: a systematic review and meta-analysis

Background The effect of stress on Graves’ disease (GD) is controversial. Our purpose was to quantify the impacts of stress on patients with Graves’ disease. Methods Systematic searches of PubMed, MEDLINE, Embase, Web of Science, Scopus, Cochrane Library and PsycInfo were conducted from inception to 1 January 2023. Studies comparing the incidence of stressful life events (SLEs) that occurred before diagnosis and during drug therapy in cases diagnosed with GD and controls were included in the final analysis. Results Nine case-control studies and four cohort studies enrolling 2892 participants (1685 [58%] patients) were included. Meta-analysis revealed a high and significant effect-size index in a random effect model (d = 1.81, P = 0.01), indicating that stress is an important factor in the onset of GD. The relationship between SLEs and GD was stronger in studies with higher proportions of female patients (β = 0.22, P < 0.01) and weaker in studies with older patients with GD (β =−0.62, P < 0.01). However, stress did not significantly affect the outcome of antithyroid drug therapy for GD (d = 0.32, P = 0.09). Conclusions The results of this meta-analysis suggest that stress is one of the environmental triggers for the onset of GD. Therefore, we recommend stress management assistance for individuals genetically susceptible to GD, especially for young females.