title: Plasma levels of adiponectin and soluble thrombomodulin in hypothyroid patients with normal thyroid function following levothyroxine replacement therapy.
abstract: Hypothyroidism is associated with increased morbidity from cardiovascular disease, and adiponectin (ApN) is a newly-identified adipocytokine, which is expressed in human adipose cells and may have a protective effect against the development of coronary artery disease. The aim of the study was to evaluate the involvement of ApN secretion in hypothyroid patients with normal thyroid function following levothyroxine (L-T(4)) replacement therapy, and to associate plasma ApN levels with intima-media thickness (IMT) in the common carotid artery (CCA), an indicator of early atherosclerosis, and cardiovascular parameters including soluble thrombomodulin (sTM), a plasma endothelial injury marker. The CCA IMT and plasma levels of ApN and sTM were measured in 52 hypothyroid patients and in age-, sex- and body mass index (BMI)-matched normal control subjects. Thirty-six of the hypothyroid patients were further monitored for changes in these markers during 1 year in a euthyroid state induced by L-T(4) replacement therapy. Although the basal CCA IMT was significantly higher in hypothyroid patients [0.633 +/- 0.018 mm (mean +/- S.E.)] than in control subjects (0.552 +/- 0.022 mm, P < 0.005), both groups had similar baseline ApN and sTM levels [10.23 +/- 0.76 vs. 10.10 +/- 0.93 microg/ml: NS; and 2.58 +/- 0.14 vs. 2.68 +/- 0.20 ng/ml: NS, respectively]. Simple regression analysis revealed that plasma ApN was significantly correlated in a positive manner with age (r = 0.339, P = 0.015), HDL-cholesterol (r = 0.295, P = 0.048), and sTM (r = 0.490, P = 0.0005), but not with CCA IMT (r = 0.059, P = 0.742). In multivariate analysis, the plasma ApN level was significantly associated with that of sTM (r = 0.546, P = 0.0001) and with serum high-density lipoprotein (HDL)-cholesterol levels (r = 0.291, P = 0.029) in hypothyroid patients. During 1 year of L-T(4) replacement therapy, hypothyroid patients showed a significant decrease in CCA IMT, to 0.553 +/- 0.016 mm (P < 0.0001), a level comparable to normal controls, but no significant change in ApN (from 10.79 +/- 1.07 to 10.6 9+/- 1.14 microg/ml, NS) or sTM (from 2.59 +/- 0.15 to 2.74 +/- 0.18 ng/ml, NS). Hence, we provide evidence that ApN and sTM might not contribute to enhanced atherosclerosis, as reflected by increased CCA IMT in hypothyroid patients. However, this is the first report to demonstrate a positive and significant association of sTM with ApN. These data support the hypothesis that sTM is one of the determinant of ApN and thus suggest the presence of an sTM-associated regulatory mechanism for ApN secretion in hypothyroid patients.
authors.affiliation: Department of Metabolism, Endocrinology and Molecular Medicine, Internal Medicine, 1-4-3, Asahi-machi, Osaka 545-8585, Japan.
authors.forename: Toshiki
authors.initials: T
authors.lastname: Nagasaki
authors.forename: Masaaki
authors.initials: M
authors.lastname: Inaba
authors.forename: Yoshikazu
authors.initials: Y
authors.lastname: Hiura
authors.forename: Hideki
authors.initials: H
authors.lastname: Tahara
authors.forename: Yasuro
authors.initials: Y
authors.lastname: Kumeda
authors.forename: Kumi
authors.initials: K
authors.lastname: Shirakawa
authors.forename: Naoyoshi
authors.initials: N
authors.lastname: Onoda
authors.forename: Tetsuro
authors.initials: T
authors.lastname: Ishikawa
authors.forename: Eiji
authors.initials: E
authors.lastname: Ishimura
authors.forename: Yoshiki
authors.initials: Y
authors.lastname: Nishizawa
mesh_terms: D052242:Adiponectin / Q000097:blood; D002340:Carotid Artery Diseases / Q000097:blood / Q000000981:diagnostic imaging / Q000517:prevention & control; D017536:Carotid Artery, Common / Q000000981:diagnostic imaging; D005260:Female; D020249:Hormone Replacement Therapy; D006801:Humans; D007037:Hypothyroidism / Q000097:blood / Q000000981:diagnostic imaging / Q000188:drug therapy*; D008297:Male; D011446:Prospective Studies; D012044:Regression Analysis; D018180:Thrombomodulin / Q000097:blood*; D013974:Thyroxine / Q000627:therapeutic use*; D017539:Tunica Intima / Q000000981:diagnostic imaging; D017540:Tunica Media / Q000000981:diagnostic imaging; D014463:Ultrasonography
chemical_list: C499918:ADIPOQ protein, human; D052242:Adiponectin; D018180:Thrombomodulin; D013974:Thyroxine