Health Consequences of Thymus Removal in Adults.
Level 3 - non-randomized controlled study
Retrospective matched cohort study comparing surgical patients with and without thymectomy
PubMed 37530823 · doi:10.1056/NEJMoa2302892
What was done
Researchers evaluated long-term health risks in adult patients who underwent thymectomy compared with demographically matched control patients who underwent cardiothoracic surgery without thymectomy. From an initial pool of 1,420 thymectomy patients and 6,021 controls, a primary matched cohort of 1,146 pairs was analyzed for all-cause mortality, cancer incidence, and autoimmune disease. A subgroup of 41 patients (22 thymectomy, 19 controls) with a mean follow-up of 14.2 years underwent biomarker testing for T-cell production (signal joint T-cell receptor excision circles, sjTREC) and circulating cytokine levels.
What was found
At 5 years post-surgery, all-cause mortality was significantly higher in the thymectomy group than in controls (8.1% vs. 2.8%; relative risk [RR] 2.9, 95% CI 1.7 to 4.8), as was the risk of developing cancer (7.4% vs. 3.7%; RR 2.0, 95% CI 1.3 to 3.2). Autoimmune disease risk did not differ significantly overall (RR 1.1, 95% CI 0.8 to 1.4), but was elevated among thymectomy patients when those with preoperative infection, cancer, or autoimmunity were excluded (12.3% vs. 7.9%; RR 1.5, 95% CI 1.02 to 2.2). In patients with over 5 years of follow-up, mortality exceeded general U.S. population rates (9.0% vs. 5.2% all-cause; 2.3% vs. 1.5% cancer mortality). Subgroup testing showed thymectomy patients had significantly lower sjTREC counts for CD4+ (526 vs. 1,451 per microgram DNA, P=0.009) and CD8+ lymphocytes (447 vs. 1,466 per microgram DNA, P<0.001), alongside higher proinflammatory cytokine levels.
Why it matters
Routine removal of the adult thymus during cardiothoracic surgery has long been considered immunologically inconsequential. These findings suggest the adult thymus remains critical for maintaining peripheral T-cell diversity and immune homeostasis, and its removal may carry substantial long-term health risks.
Limits
The study is observational and retrospective, leaving room for residual confounding by indication, underlying surgical pathology, or baseline health status despite demographic matching. The mechanistic subgroup assessing T-cell production and cytokines was small (n = 41). Specific surgical indications and direct cause-specific mortality details were not fully delineated in the abstract.