title: Endocan, TGF-beta, and ADMA as Risk Factors for Endothelial Dysfunction and Possible Vascular Disease in Patients with Subclinical Hypothyroidism.
abstract: OBJECTIVE
  Although the relationship between atherosclerosis and overt hypothyroidism has been confirmed, it remains controversial in cases of subclinical hypothyroidism. Higher TSH and similar T4 suggest differences in set-points or differences due to diagnostic limitations regarding subclinical hypothyroidism. Endothelial dysfunction (ED) is a marker rather than a precursor of cardiovascular disease. Asymmetric dimethylarginine (ADMA) and endocan are known as novel markers of ED in various diseases. Transforming growth factor-beta (TGF-β) has a protective role against autoimmune diseases such as thyroiditis. This study aimed to determine the relationships between serum ADMA, endocan, TGF-β, and the high-sensitivity C-reactive protein (hs-CRP) levels, a proven indicator of ED, in patients with SH.
  
  
  METHODS
  Thirty-five patients with SH and 21 age- and sex-matched euthyroid subjects were included in the study. The levels of TSH, FT4, lipid parameters, endocan, ADMA, TGF-β, and hs-CRP were measured.
  
  
  RESULTS
  No significant differences in age or sex were found between the patient and control groups (p=0.294 and 0.881, respectively). Mean TSH level was higher in the patient group (p=0.005), whereas mean fT4 level was similar in two groups (p=0.455). The average hs-CRP, endocan, TGF-β l level in the patient group was higher than control group (p=0.001; P=0.012; P=0.025; P<0.01 respectively). A positive correlation was found between the endocan and ADMA levels (r=0.760, p=0.000). ADMA levels also were positively correlated with hs-CRP. Both the TSH and low-density lipoprotein cholesterol (LDL-C) levels were positively correlated with the hs-CRP level.
  
  
  CONCLUSIONS
  Subclinical hypothyroidism is associated with increased levels of serum endocan, ADMA, and TGF-β, which are new markers for ED. In particular, ADMA was correlated with both endocan and hs-CRP levels. These findings are suggestive for increased risk of ED and subsequent development of atherosclerosis in patients with SH.
authors.affiliation: Division of Endocrinology and Metabolism, Department of Internal Medicine, Faculty of Medicine, Bulent Ecevit University, Zonguldak, Turkey drarpaci@gmail.com.
authors.forename: Dilek
authors.initials: D
authors.lastname: Arpaci
authors.affiliation: Department of Microbiology, Faculty of Medicine, Sakarya University Education and Research Hospital, Sakarya, Turkey.
authors.forename: Engin
authors.initials: E
authors.lastname: Karakece
authors.affiliation: Department of Internal Medicine, Faculty of Medicine, Sakarya University Education and Research Hospital, Sakarya, Turkey.
authors.forename: Aysel Gurkan
authors.initials: AG
authors.lastname: Tocoglu
authors.affiliation: Department of Internal Medicine, Faculty of Medicine, Sakarya University Education and Research Hospital, Sakarya, Turkey.
authors.forename: Hasan
authors.initials: H
authors.lastname: Ergenc
authors.affiliation: Department of Physiology, Faculty of Medicine, Sakarya University Education and Research Hospital, Sakarya, Turkey.
authors.forename: Gonul
authors.initials: G
authors.lastname: Gurol
authors.affiliation: Department of Microbiology, Faculty of Medicine, Sakarya University Education and Research Hospital, Sakarya, Turkey.
authors.forename: Ihsan Hakki
authors.initials: IH
authors.lastname: Ciftci
authors.affiliation: Department of Internal Medicine, Faculty of Medicine, Sakarya University Education and Research Hospital, Sakarya, Turkey.
authors.forename: Ali
authors.initials: A
authors.lastname: Tamer
mesh_terms: D000328:Adult; D001120:Arginine / Q000031:analogs & derivatives* / Q000097:blood; D015415:Biomarkers / Q000097:blood; D003710:Demography; D004730:Endothelium, Vascular / Q000473:pathology / Q000503:physiopathology*; D005260:Female; D006801:Humans; D007037:Hypothyroidism / Q000097:blood* / Q000150:complications / Q000503:physiopathology*; D007249:Inflammation; D008297:Male; D009363:Neoplasm Proteins / Q000097:blood*; D011509:Proteoglycans / Q000097:blood*; D012307:Risk Factors; D013960:Thyroid Function Tests; D016212:Transforming Growth Factor beta / Q000097:blood*; D014652:Vascular Diseases / Q000097:blood* / Q000150:complications / Q000503:physiopathology*
chemical_list: D015415:Biomarkers; C101134:ESM1 protein, human; D009363:Neoplasm Proteins; D011509:Proteoglycans; D016212:Transforming Growth Factor beta; C018524:N,N-dimethylarginine; D001120:Arginine
keywords: ADMA; Endocan; Subclinical Hypothyroidism; TGF-beta