title: L-Arginine Derivatives Are Associated with the Hyperthyroid State in the General Population.
abstract: 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.
authors.affiliation: 1 Institute for Community Medicine, University Medicine Greifswald , Germany .|2 Department of Internal Medicine B-Cardiology, Intensive Care, Pulmonary Medicine, and Infectious Diseases, University Medicine Greifswald , Germany .
authors.forename: Till
authors.initials: T
authors.lastname: Ittermann
authors.affiliation: 2 Department of Internal Medicine B-Cardiology, Intensive Care, Pulmonary Medicine, and Infectious Diseases, University Medicine Greifswald , Germany .|3 Division of Cardiovascular Medicine, Radcliffe Department of Medicine, University of Oxford , United Kingdom .
authors.forename: Martin
authors.initials: M
authors.lastname: Bahls
authors.affiliation: 4 Institute for Clinical Chemistry and Laboratory Medicine, University Medicine Greifswald , Germany .|5 DZHK (German Center for Cardiovascular Research) , partner site Greifswald, Germany .|6 Department of Clinical Pharmacology and Toxicology, University Medical Center Hamburg-Eppendorf , Germany .
authors.forename: Dorothee
authors.initials: D
authors.lastname: Atzler
authors.affiliation: 2 Department of Internal Medicine B-Cardiology, Intensive Care, Pulmonary Medicine, and Infectious Diseases, University Medicine Greifswald , Germany .|7 DZHK (German Center for Cardiovascular Research) , partner site Hamburg/Kiel/Lübeck, Germany .
authors.forename: Nele
authors.initials: N
authors.lastname: Friedrich
authors.affiliation: 5 DZHK (German Center for Cardiovascular Research) , partner site Greifswald, Germany .|6 Department of Clinical Pharmacology and Toxicology, University Medical Center Hamburg-Eppendorf , Germany .
authors.forename: Edzard
authors.initials: E
authors.lastname: Schwedhelm
authors.affiliation: 5 DZHK (German Center for Cardiovascular Research) , partner site Greifswald, Germany .|6 Department of Clinical Pharmacology and Toxicology, University Medical Center Hamburg-Eppendorf , Germany .
authors.forename: Rainer H
authors.initials: RH
authors.lastname: Böger
authors.affiliation: 2 Department of Internal Medicine B-Cardiology, Intensive Care, Pulmonary Medicine, and Infectious Diseases, University Medicine Greifswald , Germany .|3 Division of Cardiovascular Medicine, Radcliffe Department of Medicine, University of Oxford , United Kingdom .
authors.forename: Stephan B
authors.initials: SB
authors.lastname: Felix
authors.affiliation: 1 Institute for Community Medicine, University Medicine Greifswald , Germany .|2 Department of Internal Medicine B-Cardiology, Intensive Care, Pulmonary Medicine, and Infectious Diseases, University Medicine Greifswald , Germany .
authors.forename: Henry
authors.initials: H
authors.lastname: Völzke
authors.affiliation: 2 Department of Internal Medicine B-Cardiology, Intensive Care, Pulmonary Medicine, and Infectious Diseases, University Medicine Greifswald , Germany .|3 Division of Cardiovascular Medicine, Radcliffe Department of Medicine, University of Oxford , United Kingdom .
authors.forename: Marcus
authors.initials: M
authors.lastname: Dörr
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001120:Arginine / Q000008:administration & dosage* / Q000031:analogs & derivatives / Q000097:blood; D050197:Atherosclerosis / Q000097:blood*; D003430:Cross-Sectional Studies; D005260:Female; D005858:Germany; D006801:Humans; D006980:Hyperthyroidism / Q000097:blood*; D008297:Male; D008875:Middle Aged; D012044:Regression Analysis; D013960:Thyroid Function Tests; D013961:Thyroid Gland / Q000502:physiology; D013972:Thyrotropin / Q000097:blood; D013974:Thyroxine / Q000097:blood; D014284:Triiodothyronine / Q000097:blood; D055815:Young Adult
chemical_list: D014284:Triiodothyronine; C024917:symmetric dimethylarginine; C018524:N,N-dimethylarginine; D013972:Thyrotropin; D001120:Arginine; D013974:Thyroxine