Pre-diagnostic vitamin D deficiency and subsequent thyroid cancer risk: a propensity-matched cohort study

Background: Vitamin D deficiency (VDD) has been implicated as a potential risk factor for thyroid cancer; however, existing evidence is derived primarily from case-control or cross-sectional studies. This study aimed to examine the association between pre-diagnostic VDD and the risk of incident thyroid cancer over a 10-year follow-up period. Methods: This retrospective propensity score-matched cohort study used the TriNetX Global Collaborative Network. Adults aged ≥ 18 y with serum 25-hydroxyvitamin D [25(OH)D] measurements between 2010 and 2023 were classified as having VDD (<20 ng/mL) or vitamin D sufficiency (≥30 ng/mL). One-to-one propensity score matching was performed on demographics, comorbidities, thyroid-related disorders, laboratory values, and vitamin D supplementation. The primary outcome was incident thyroid cancer ascertained ≥ 180 day after the index date (landmark approach) over 10 y of follow-up. Positive (osteoporotic fracture) and negative (appendicitis, goiter) control outcomes and thyroid procedure utilization were evaluated to assess detection bias. Results: After matching, 571,669 pairs were analyzed over a median follow-up of 6.8 y. VDD was associated with an increased risk of incident thyroid cancer (HR: 1.41; 95% CI: 1.32, 1.50), and this risk was attenuated among patients with vitamin D insufficiency (25[OH]D 20-30 ng/mL; HR: 1.27; 95% CI: 1.20, 1.34), demonstrating a dose-dependent relationship. Thyroid biopsy and ultrasonography utilization were lower in the VDD cohort (HR: 0.95), arguing against detection bias. The positive control outcome (osteoporotic fracture; HR: 1.53) confirmed the validity of the exposure classification, whereas the negative control (appendicitis; HR: 1.02) showed no association. Findings were robust across all sensitivity and subgroup analyses. Conclusion: Pre-diagnostic VDD was associated with increased thyroid cancer risk in a dose-dependent manner. These findings support further investigation of vitamin D status as a potentially modifiable risk factor for thyroid cancer.