title: Normalization of hyperhomocysteinemia with L-thyroxine in hypothyroidism.
abstract: BACKGROUND
  Hyperhomocysteinemia is an independent risk factor for coronary, peripheral, and cerebrovascular disease. Elevated plasma homocysteine levels were described in a preliminary report on primary hypothyroidism.
  
  
  OBJECTIVE
  To determine whether restoration of euthyroidism by L-thyroxine replacement therapy would reduce or normalize plasma homocysteine levels.
  
  
  METHODS
  Prospective cohort study.
  
  
  METHODS
  Outpatient endocrinology department of a tertiary center.
  
  
  METHODS
  14 patients (10 women and 4 men; 25 to 77 years of age): 4 with newly diagnosed chronic (Hashimoto) hypothyroidism and 10 who had been rendered acutely hypothyroid (thyroid-stimulating hormone level > 25 mU/L) by total thyroidectomy for thyroid carcinoma.
  
  
  METHODS
  Total plasma homocysteine levels were measured at baseline and 3 to 9 months later, after euthyroidism had been attained by L-thyroxine replacement therapy.
  
  
  RESULTS
  Median baseline plasma homocysteine levels in both sexes (women, 11.65 micromol/L [range, 7.2 to 26.5 micromol/L]; men, 15.1 micromol/L [range, 14.1 to 16.3 micromol/L]) were higher (P = 0.002) than those in healthy female (n = 35) and male (n = 36) volunteers (women, 7.52 micromol/L [range, 4.3 to 14.0 micromol/L]; men, 8.72 micromol/L [range, 5.94 to 14.98 micromol/L]). Eight patients (57%) had baseline plasma homocysteine levels that exceeded the upper limit of sex-specific reference ranges. Upon attainment of euthyroidism, all patients had a diminution in plasma homocysteine levels. The median overall change of -5.5 micromol/L (range, -15.4 to -1.8 micromol/L) corresponds to a difference of -44% (range, -58% to -13%) (P < 0.001). Homocysteine levels returned to normal in 7 of the 8 patients with elevated pretreatment values.
  
  
  CONCLUSIONS
  Hypothyroidism may be a treatable cause of hyperhomocysteinemia, and elevated plasma homocysteine levels may be an independent risk factor for the accelerated atherosclerosis seen in primary hypothyroidism.
authors.affiliation: The Cleveland Clinic Foundation, Ohio 44195, USA.
authors.forename: W I
authors.initials: WI
authors.lastname: Hussein
authors.forename: R
authors.initials: R
authors.lastname: Green
authors.forename: D W
authors.initials: DW
authors.lastname: Jacobsen
authors.forename: C
authors.initials: C
authors.lastname: Faiman
mesh_terms: D000328:Adult; D000368:Aged; D005260:Female; D006710:Homocysteine / Q000097:blood*; D006801:Humans; D020138:Hyperhomocysteinemia / Q000150:complications* / Q000378:metabolism; D007037:Hypothyroidism / Q000097:blood / Q000150:complications* / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D013974:Thyroxine / Q000627:therapeutic use*
chemical_list: D006710:Homocysteine; D013974:Thyroxine