Homocysteine, Hypothyroidism, and Effect of Thyroid Hormone Replacement

Abstract

Elevation of total plasma concentration of homocysteine (t-Hcy) is an important and independent risk factor for cardiovascular disease. Hypothyroidism is possibly also associated with an increased risk for coronary artery disease, which may be related to atherogenic changes in lipid profile. Because hypothyroidism decreases hepatic levels of enzymes involved in the remethylation pathway of homocysteine, we prospectively evaluated fasting and postload t-Hcy in patients before and after recovery of euthyroidism. Fasting and postload t-Hcy levels were higher in 40 patients with peripheral hypothyroidism (14 with autoimmune thyroiditis and 26 treated for thyroid cancer) in comparison with those of 26 controls (13.0 +/- 7.5 vs. 8.5 +/- 2.6 micromol/L, p < .01, respectively, and 49.9 +/- 37.3 vs. 29.6 +/- 8.4 micromol/L p < .001, respectively). On univariate analysis, fasting Hcy was positively related to thyrotropin (TSH) and inversely related to folates. Multivariate analysis confirmed TSH as the strongest predictor of t-Hcy independent of age, folate, vitamin B12, and creatinine. Thyroid hormone replacement significantly decreased fasting but not postload t-Hcy. We conclude that t-Hcy is elevated in hypothyroidism. The association of hyperhomocysteinemia and lipid abnormalities occurring in hypothyroidism may represent a dynamic atherogenic state. Thyroid hormone failed to completely normalize t-Hcy. Potential benefit of treatment with folic acid in combination with thyroid hormone replacement has to be tested given that hypothyroid patients were found to have lower levels of folate.

Homocysteine, Folate and Cobalamin Levels in Hypothyroid Women before and after Treatment

“…In univariate analysis the serum levels of thyroid hormones and TSH were significant determinants of plasma tHcy. These observations are consistent with the results of other authors [5,22,23]. Nedrebo et al demonstrated that tHcy level was significantly higher in patients with hypothyroidism, than in the group with hyperthyroidism.…”

“…This observation is not in agreement with other authors [23,26]. Catargi et al found lower levels of folate in hypothyroid patients and in univariate analysis tHcy was significantly negatively associated with folate levels [22]. Recently, Ozmen et al reported low folate levels in hypothyroidism and concluded that hyperhomocysteinemia in hypothyroidism is associated with an altered folate status [34].…”

Correlation of serum homocysteine levels and pregnancy outcome: the dilemma continues

“…Against our study Catarqi et al in 1999 found that homocysteine level to be elevated in hypothyroid cases. 16 They postulated that hypothyroidism decreases hepatic levels of enzymes involved in remethylation pathway of homocysteine. Similarly Diekman et al concluded that plasma homocysteine levels increased in hypothyroidism.…”

Plasma Homocysteine Levels in Hyperthyroid Patients

“…Homocysteine is metabolized by one of the two pathways: remethylation and trans-sulphuration [1,2]. Hyperhomocysteinemia is an independent risk factor for atherosclerosis and atherothrombosis [3][4][5][6][7]. Although the molecular mechanism by which homocysteine or a related metabolite promotes atherothrombosis is unknown, the epidemiologic evidence of the association of hyperhomocysteinemia with atherothrombotic vascular disease is convincing [1].…”