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.
Design: Prospective cohort study.
Setting: Outpatient endocrinology department of a tertiary center.
Patients: 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 levelÂ >Â 25 mU/L) by total thyroidectomy for thyroid carcinoma.
Measurements: 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 Âµmol/L [range, 7.2 to 26.5 Âµmol/L]; men, 15.1 Âµmol/L [range, 14.1 to 16.3 Âµmol/L]) were higher (PÂ =Â 0.002) than those in healthy female (nÂ =Â 35) and male (nÂ =Â 36) volunteers (women, 7.52 Âµmol/L [range, 4.3 to 14.0 Âµmol/L]; men, 8.72 Âµmol/L [range, 5.94 to 14.98 Âµmol/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 âˆ’5.5 Âµmol/L (range, âˆ’15.4 to âˆ’1.8 Âµmol/L) corresponds to a difference of âˆ’44% (range, âˆ’58% to âˆ’13%) (PÂ <Â 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.