Abstract
ImportanceTonsillectomy has long been scrutinized for its potential long-term impacts on health, with conflicting evidence linking it to increased risks of several diseases, such as cancer, psychiatric disorders, and immune dysfunctions.ObjectiveTo comprehensively analyze the effects of tonsillectomy on various disease outcomes.DesignLongitudinal cohort study, 2-sample Mendelian randomization (MR) analysis, and multivariable MR (MVMR) analysis.SettingThe UK Biobank.ParticipantsAll UK Biobank (UKB) participants who did not withdraw from the UKB were included. Individuals diagnosed with benign or malignant tonsil tumors, with conflicting information regarding the timing of tonsillectomy, a history of adenoidectomy without tonsillectomy, and incomplete data on birth year, sex, and ethnic background were excluded.Intervention or exposuresTonsillectomy.Main outcome measuresIncident diseases diagnosed based on International Classification of Diseases diagnostic codes and self-reported doctor-diagnosed disease histories.ResultsTonsillectomy was significantly associated with 17 primary core outcomes (incidence ≥ 1%, P < .001, hazards ratio [HR] ≥ 1.10 or HR ≤ 0.90) among the general population. Among individuals with tonsillitis, those who underwent tonsillectomy were at greater risk of developing 7 secondary core outcomes than those who did not have the surgery. To assess potential causal associations, we performed 2-sample MR analysis and observed that tonsillectomy was causally associated with asthma, depression, irritable bowel syndrome (IBS), and anxiety. Additionally, tonsillitis was causally associated with depression, IBS, and anxiety. However, when applying MVMR analysis to account for potential confounders, the causal relationship between tonsillectomy or tonsillitis and depression or anxiety were no longer observed. Notably, tonsillitis remained causally associated with IBS in the MVMR analysis.ConclusionsThese findings suggest that the observed associations between tonsillectomy and various disease outcomes may be more attributable to the underlying effects of tonsillitis, rather than causal effects of the surgery itself. This evidence supports the safety of tonsillectomy in clinical practice.RelevanceThe findings of this study addressed the concerns about the adverse effects of tonsillectomy, supporting the safety of tonsillectomy in clinical practice.