The development of thyroid autoimmunity is potentially associated with the deficiency of vitamin D3 rather than vitamin D2 in euthyroid men.

Objective: Vitamin D(VitD) deficiency has been found prevalent among patients with thyroid autoimmunity (TAI). This study aimed to investigate whether low VitD2 or VitD3 potentially contributed to the development of TAI in euthyroid male patients, which had not been reported before.

Methods: A total of 2882 euthyroid male petroleum workers were recruited from those participants in the healthcare program at the second affiliated hospital of Dalian Medical University in 2021, whose serum VitD levels, thyroid functions, and autoantibody titers were all examined at the same time. Among them, 2587 (89.8%) individuals received the second health follow-up in 2022. Serum VitD including 25(OH)D2 (VitD2) and 25(OH)D3 (VitD3) levels were detected by liquid chromatography-tandem mass spectrometry. Thyroid functions and autoantibody titers were quantified using chemiluminescent immunoassays.

Results: The serum levels of VitD and VitD3 were pronouncedly lower in the male euthyroid subjects with TAI (n = 195) than those non-TAI men (n = 2687, P < 0.05), whereas serum VitD2 was not significantly different based on the data from the initial investigation in 2021. The prevalence of subjects with TAI among the total male euthyroid subjects with TAI population was markedly increased with the decreasing levels of serum VitD and VitD3, respectively (P for trend < 0.05), but not significantly changed with that of serum VitD2. The binary logistic regression analysis revealed that either the deficiency of VitD (serum VitD < 20 ng/mL, VDD) or low VitD3 level was an independent risk factor for the development of TAI, which had been further demonstrated by the follow-up observation in 2022. Among the non-TAI men in 2021, 6.52% (n = 157) individuals became TAI patients after a one-year follow-up, and their serum VitD and VitD3 levels both exhibited significantly more reduction as compared with those of the remained non-TAI ones in 2022. More of those with VDD developed TAI than the non-VDD ones did in 2022 (8.5% vs. 5.6%, P<0.05). Additionally, the change in serum VitD over the two years was more strongly correlated with serum VitD3 (rs = 0.971, P < 0.001) when compared with that of VitD2 (rs = 0.085, P < 0.001) in the whole euthyroid male population.

Conclusion: Based on the cross-sectional and prospective investigations, our findings further indicate that VDD may be an independent risk factor for TAI development. Moreover, the latter is potentially associated with the deficiency of VitD3 rather than VitD2 in the euthyroid male population although the related mechanisms await in-depth exploration. Our findings also suggest that VitD3 supplementation might provide more potential benefits than VitD2 among VDD men in terms of preventing TAI development.

Study Registration: the Dalian Health Management Cohort (DHMC) ChiCTR2300073363.