title: Effect of thyroid hormone replacement on methionine-stimulated homocysteine levels in patients with subclinical hypothyroidism: a randomized, double-blind, placebo-controlled study.
abstract: OBJECTIVE
  To determine whether treatment of subclinical hypothyroidism with levothyroxine would improve homocysteine metabolism.
  
  
  METHODS
  Twenty-four patients with subclinical hypothyroidism who had thyrotropin (thyroid-stimulating hormone or TSH) levels between 5 and 10 microIU/mL and normal free thyroxine concentrations were recruited from a primary care clinic and were randomized to receive levothyroxine (N = 12) or placebo (N = 12) for a period of 6 months in a double-blind, placebo-controlled study. Homocysteine was measured during fasting and after methionine challenge at the beginning and the end of the study in all patients treated with levothyroxine or placebo.
  
  
  RESULTS
  The 12 patients treated with levothyroxine had normal TSH levels at the end of the study, with a median value of 1.8 microIU/mL. The 12 patients receiving placebo had a median TSH of 6.0 microIU/mL after the 6-month study period. The ratio of fasting homocysteine at 6 months in comparison with baseline was 1.16 (95% confidence interval, 0.90 to 1.63) for the levothyroxine-treated group and 1.00 (0.88 to 1.29) for the placebo group (P = 0.95). The ratio of post-methionine homocysteine at 6 months in comparison with baseline was 1.00 (95% confidence interval, 0.92 to 1.35) for the levothyroxine-treated group and 0.89 (0.68 to 1.05) for the placebo group (P = 0.081).
  
  
  CONCLUSIONS
  In this study, levothyroxine treatment of patients with subclinical hypothyroidism did not alter homocysteine levels in the fasting or post-methionine states.
authors.affiliation: Division of Endocrinology, Mayo Clinic College of Medicine, Jacksonville, Florida 32224-1865, USA.
authors.forename: Shon
authors.initials: S
authors.lastname: Meek
authors.forename: Robert C
authors.initials: RC
authors.lastname: Smallridge
mesh_terms: D000328:Adult; D000368:Aged; D003404:Creatinine / Q000097:blood; D004311:Double-Blind Method; D005215:Fasting / Q000097:blood; D005260:Female; D005492:Folic Acid / Q000097:blood; D006710:Homocysteine / Q000097:blood*; D020249:Hormone Replacement Therapy; D006801:Humans; D007037:Hypothyroidism / Q000097:blood* / Q000188:drug therapy*; D008297:Male; D008715:Methionine / Q000494:pharmacology*; D008875:Middle Aged; D015990:Placebo Effect; D013963:Thyroid Hormones / Q000494:pharmacology* / Q000627:therapeutic use*; D013972:Thyrotropin / Q000097:blood; D013974:Thyroxine / Q000097:blood / Q000627:therapeutic use; D014805:Vitamin B 12 / Q000097:blood
chemical_list: D013963:Thyroid Hormones; D006710:Homocysteine; D013972:Thyrotropin; D005492:Folic Acid; D008715:Methionine; D003404:Creatinine; D014805:Vitamin B 12; D013974:Thyroxine