Normalization of Hyperhomocysteinemia with l-thyroxine in Hypothyroidism

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Abstract
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. To determine whether restoration of euthyroidism by l-thyroxine replacement therapy would reduce or normalize plasma homocysteine levels. Prospective cohort study. Outpatient endocrinology department of a tertiary center. 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. Total plasma homocysteine levels were measured at baseline and 3 to 9 months later, after euthyroidism had been attained by l-thyroxine replacement therapy. Median baseline plasma homocysteine levels in both sexes (women, 11.65 µmol/L [range, 7.2 to 26.5 µmol/L]; men, 15.1 µmol/L [range, 14.1 to 16.3 µmol/L]) were higher (P = 0.002) than those in healthy female (n = 35) and male (n = 36) volunteers (women, 7.52 µmol/L [range, 4.3 to 14.0 µmol/L]; men, 8.72 µmol/L [range, 5.94 to 14.98 µmol/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 µmol/L (range, −15.4 to −1.8 µmol/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. 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.