Obesity as a Predictor of Hypothyroidism: A Mendelian Randomization Perspective

Dr Nitin Kapoor, Professor and Head(Unit 1), Dept. of Endocrinology, Diabetes and Metabolism, Christian Medical College, Vellore (TN) India.

“A study published in the Critical Public Health reported that excess adiposity drives thyroid dysfunction through metabolic and inflammatory pathways, highlighting the essential role of weight management.”

Hypothyroidism is caused by reduced thyroid hormone production and is more prevalent in women. It contributes to metabolic slowing and increases cardiovascular risks through its effects on lipid levels, blood pressure, and systemic inflammation. Obesity has been increasingly recognized as both a consequence and a potential driver of thyroid dysfunction. Excess body fat promotes chronic low-grade inflammation and elevates leptin levels, which may disrupt the hypothalamic–pituitary–thyroid axis and impair hormone regulation.

To clarify whether obesity directly increases the risk of hypothyroidism, a two-sample Mendelian randomization (MR) study was conducted using genome-wide significant genetic variants associated with body fat percentage from the IEU Open GWAS database. The hypothyroidism dataset included 22,687 cases and 440,246 controls. Out of the the 395 single Nucleotide Polymorphisms (sNPs)  initially identified, 394 were retained after excluding variants with direct associations with the outcome. Ethical approval for the study was obtained from the Second Xiangya Hospital ethics committee.

Across multiple MR approaches—including inverse-variance weighted, MR-Egger, and weighted median—higher body fat percentage showed a significant causal effect on increased hypothyroidism risk. Although some heterogeneity and pleiotropy were present, correction and sensitivity analyses confirmed that the causal estimates remained robust.

Together these results conclude that excess adiposity contributes to thyroid dysfunction through metabolic and inflammatory pathways and emphasize the importance of weight management in thyroid health assessments.

(Source: Zhang S, Zhang Z, Xiao Y, Chen M, Hu L, Tang H, Li X. Causal link between obesity and the risk of hypothyroidism: a two-sample Mendelian randomization study. Crit Public Health. 2025;35(1). doi:10.1080/09581596.2025.2571874; https://www.tandfonline.com/doi/epdf/10.1080/09581596.2025.2571874?needAccess=true)