Thyroid cancer risk in systemic lupus erythematosus: A population-based retrospective cohort study.

e18043 Background: Systemic lupus erythematosus (SLE) is a chronic autoimmune disease marked by immune dysregulation and long-standing inflammation, factors that may contribute to an increased risk of malignancy. Although SLE has been linked to several cancers, population-level data specifically examining the risk of thyroid cancer in patients with SLE remain limited. Methods: We performed a retrospective cohort study using the TriNetX Global Collaborative Network, a federated electronic health record database comprising multiple international healthcare organizations. Adults aged 18–49 years between January 1, 2015, and December 31, 2025, were included. Patients with SLE were identified using the ICD-10 code M32, with the earliest recorded diagnosis serving as the index date. A comparator cohort without any recorded diagnosis of SLE was constructed from the same network. Patients with a history of thyroid cancer before cohort entry were excluded to ensure assessment of incident disease. The primary outcome was incident thyroid cancer, identified using ICD-O-3 code C73. Incidence proportions and incidence rates (cases per person-day) were calculated and stratified by age, sex, race, and ethnicity. Results: The analysis included 102,072 patients with SLE and 34,755,380 patients without SLE. Patients with SLE had a substantially higher incidence of thyroid cancer than those without SLE. The incidence proportion of thyroid cancer was 0.000098 in the SLE cohort compared with 0.00000471 in the non-SLE cohort, corresponding to an approximately 20-fold higher incidence among patients with SLE. The incidence rates were 0.0000000431 and 0.00000000377 cases per person-day, respectively. Thyroid cancer occurred almost exclusively among female patients in both cohorts, with the highest incidence observed in females with SLE. Age-stratified analyses showed that the excess risk in the SLE cohort was most pronounced among patients aged 25–39 years, while incidence remained consistently low across all age groups in the non-SLE cohort. Conclusions: In this large real-world cohort, systemic lupus erythematosus was associated with a markedly increased incidence of thyroid cancer, particularly among young and middle-aged women. These findings support a potential link between systemic autoimmunity and thyroid carcinogenesis and underscore the need for future adjusted analyses to better define underlying mechanisms and clinical implications.