L-Arginine Derivatives Are Associated with the Hyperthyroid State in the General Population

BACKGROUND: Arginine (ARG) derivatives and thyroid function independently influence atherosclerotic processes. Since thyroid hormones may mediate the association between ARG derivatives and atherosclerosis, this study investigated whether asymmetric and symmetric dimethylarginines (ADMA and SDMA, respectively) as well as homoarginine (hARG) are associated with parameters of thyroid function in the general population.

METHODS: Cross-sectional data from 3689 individuals aged 20-81 years from the population-based Study of Health in Pomerania (SHIP-0) were analyzed. Thyroid function was defined according to serum concentrations of thyrotropin (TSH), free triiodothyronine (fT3), and free thyroxine (fT4). Low and high serum TSH were defined by the cutoffs 0.3 mIU/L and 3 mIU/L, respectively. Serum concentrations of ARG, ADMA, SDMA, and hARG were measured using liquid chromatography-tandem mass spectrometry. ARG, ADMA, SDMA, and hARG were associated with serum concentrations of TSH, fT3, and fT4 by median regression and with categorized TSH values by multinomial logistic regression adjusted for age, sex, smoking status, physical activity, body mass index, and estimated glomerular filtration rate.

RESULTS: Levels of ADMA (relative risk [RR] = 5.40 [confidence interval (CI) 1.96-14.86]) and SDMA (RR = 3.55 [CI 1.01-12.70]) were associated with low TSH. In addition, ADMA (β = 0.38 [CI 0.23-0.45]) was positively associated with fT3, while both ADMA (β = 0.98 [CI 0.43-1.54]) and SDMA (β = 1.19 [CI 0.50-1.88]) were positively associated with fT4. No consistent associations of ARG and hARG with thyroid function were detected.

CONCLUSIONS: The positive associations of ADMA and SDMA with low TSH, fT3, and fT4 argue for a relationship of arginine derivatives with increased thyroid function. This suggests that the atherogenic properties of ADMA and SDMA may be partially mediated by thyroid function.