Normalization of hyperhomocysteinemia with L-thyroxine in hypothyroidism.
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.
Hussein
W I
WI
The Cleveland Clinic Foundation, Ohio 44195, USA.
Green
R
R
Jacobsen
D W
DW
Faiman
C
C
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*
D006710:Homocysteine; D013974:Thyroxine