title: Increased levels of serum osteoprotegerin in hypothyroid patients and its normalization with restoration of normal thyroid function.
abstract: Hypothyroidism is associated with increased morbidity from cardiovascular disease, and an increase in serum osteoprotegerin (OPG) has recently been reported to be associated with the severity of coronary heart disease and cardiovascular mortality. The present study was designed to examine whether hypothyroidism causes an increase in serum OPG, and to determine whether levothyroxine (L-T4) replacement therapy might suppress serum OPG levels in hypothyroid patients. Fifty-three hypothyroid patients with chronic thyroiditis and age- and sex-matched normal control subjects were examined for the levels of serum OPG and plasma von Willebrand factor (vWF), a vascular injury marker. Thirty-seven of the hypothyroid patients were further monitored for changes in these markers during 1 year in a euthyroid state induced by L-T4 replacement therapy. Baseline OPG was significantly higher in hypothyroid patients than in normal controls (4.51 +/- 0.50 vs 3.72 +/- 0.23 pmol/l (mean +/- S.E.); P = 0.0182). In multivariate analysis, baseline OPG was significantly associated with baseline levels of TSH (r = 0.280, P = 0.0162) and vWF (r = 0.626, P < 0.0001). During one year of L-T4 replacement therapy, hypothyroid patients showed a significant decrease in OPG levels from 4.35 +/- 0.51 to 3.48 +/- 0.26 pmol/l (P = 0.0166), a level comparable to normal controls. The change in serum OPG levels during L-T4 replacement therapy was significantly and independently associated in a negative fashion with baseline vWF (r = -0.503, P = 0.0014). This study suggested that the severity of hypothyroidism and vascular injury might have important independent roles in increasing the serum OPG level in hypothyroid patients. Furthermore, it was demonstrated that a sustained euthyroid state might have the potential to decrease the serum OPG level in hypothyroid patients and that the degree of vascular injury in the hypothyroid state is independently associated with a decrease in serum OPG during a 1-year normalization of thyroid function.
authors.affiliation: Department of Metabolism, Endocrinology and Molecular Medicine, Osaka City University Graduate School of Medicine, 1-4-3, Asahi-machi, Abeno-ku, Osaka 545-8585, Japan.
authors.forename: Toshiki
authors.initials: T
authors.lastname: Nagasaki
authors.forename: Masaaki
authors.initials: M
authors.lastname: Inaba
authors.forename: Shuichi
authors.initials: S
authors.lastname: Jono
authors.forename: Yoshikazu
authors.initials: Y
authors.lastname: Hiura
authors.forename: Hideki
authors.initials: H
authors.lastname: Tahara
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: D005260:Female; D006023:Glycoproteins / Q000037:antagonists & inhibitors / Q000097:blood*; D020249:Hormone Replacement Therapy; D006801:Humans; D007037:Hypothyroidism / Q000097:blood* / Q000188:drug therapy* / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D053244:Osteoprotegerin; D018160:Receptors, Cytoplasmic and Nuclear / Q000037:antagonists & inhibitors / Q000097:blood*; D018124:Receptors, Tumor Necrosis Factor; D013972:Thyrotropin / Q000097:blood; D013974:Thyroxine / Q000627:therapeutic use*; D014841:von Willebrand Factor / Q000378:metabolism
chemical_list: D006023:Glycoproteins; D053244:Osteoprotegerin; D018160:Receptors, Cytoplasmic and Nuclear; D018124:Receptors, Tumor Necrosis Factor; C506030:TNFRSF11B protein, human; D014841:von Willebrand Factor; D013972:Thyrotropin; D013974:Thyroxine