Manganese Exposure in Occupational Settings: Disruptions in Endothelial Function and Thyroid Regulation

Background: Manganese (Mn) exposure is common in welding and metal-processing occupations and has been implicated in both thyroid disruption and endothelial dysfunction through oxidative and nitric-oxide-related pathways. However, endocrine and vascular biomarkers have rarely been examined together in occupational settings. Methods: In this cross-sectional study, 95 Mn-exposed workers and 95 non-exposed controls were evaluated. Whole-blood Mn, triiodothyronine (T3), thyroxine (T4), thyroid-stimulating hormone (TSH), asymmetric dimethylarginine (ADMA), symmetric dimethylarginine (SDMA), arginine and citrulline were measured using validated Inductively Coupled Plasma-Mass Spectrometer and chemiluminescent immunoassays. Group differences were assessed using independent samples t-tests, and exposure-biomarker associations were evaluated using Pearson correlations (p < 0.05). Results: Mn-exposed workers had significantly higher blood Mn levels than controls (19.82 ± 4.54 vs. 10.22 ± 3.07 µg/L; p < 0.001). Thyroid hormones (T3, T4, and TSH) were significantly lower among Mn workers, representing a non-classical hormonal pattern, including T3 (2.47 ± 0.31 vs. 3.14 ± 0.42 ng/L; p < 0.001), T4 (1.02 ± 0.13 vs. 1.21 ± 0.18 ng/L; p < 0.001), and TSH (1.75 ± 0.53 vs. 2.88 ± 0.37 mIU/L; p < 0.001). Endothelial biomarkers also differed: ADMA (0.26 ± 0.14 vs. 0.19 ± 0.08 µmol/L; p < 0.001) and SDMA (0.24 ± 0.06 vs. 0.20 ± 0.03 µmol/L; p < 0.001) were higher, while citrulline was lower (18.77 ± 10.23 vs. 22.82 ± 6.70 µmol/L; p = 0.002). In Mn workers, blood Mn showed negative correlations with T3 (r = -0.535, p < 0.01), T4 (r = -0.331, p < 0.01), and TSH (r = -0.652, p < 0.01), and positive correlations with ADMA (r = 0.205, p < 0.05) and SDMA (r = 0.193, p < 0.05). Conclusions: These findings indicate measurable differences in thyroid hormones and dimethylarginine-related endothelial markers among Mn-exposed workers. While the cross-sectional design precludes causal inference, the combined pattern suggests a possible unusual biological response involving both endocrine regulation and nitric-oxide-related pathways. Further longitudinal studies incorporating oxidative stress markers, co-exposure assessment, and functional endothelial testing are needed to clarify the biological relevance of these associations.