Normalization of hyperhomocysteinemia with L-thyroxine in hypothyroidism

Wiam I. Hussein, Ralph Green, Donald W. Jacobsen, Charles Faiman

Research output: Contribution to journalArticlepeer-review

98 Scopus citations


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 level > 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 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. 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.

Original languageEnglish (US)
Pages (from-to)348-351
Number of pages4
JournalAnnals of Internal Medicine
Issue number5
StatePublished - Sep 7 1999

ASJC Scopus subject areas

  • Medicine(all)


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