Homocysteine, hypothyroidism, and effect of thyroid hormone replacement

Elevation of total plasma concentration of homocysteine (t-Hcy) is an impor tant and independent risk factor for cardiovascular disease. Hypothyroidism is possibly also associated with an increased risk for coronary artery dis ease, which may be related to atherogenic changes in lipid profile. Because hypothyroidism decreases hepatic levels of enzymes involved in the remethy lation pathway of homocysteine, we prospectively evaluated fasting and post load t-Hcy in patients before and after recovery of euthyroidism. Easting a nd postload t-Hcy levels were higher in 40 patients with peripheral hypothy roidism (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 mu mo l/L, P < .01, respectively, and 49.9 +/- 37.3 vs. 29.6 +/- 8.4 mu mol/L p < .001, respectively). On univariate analysis, fasting Hey was positively re lated to thyrotropin (TSH) and inversely related to folates. Multivariate a nalysis confirmed TSH as the strongest predictor of t-Hcy independent of ag e, folate, vitamin B-12, and creatinine. Thyroid hormone replacement signif icantly decreased fasting but not postload t-Hcy. We conclude that t-Hcy is elevated in hypothyroidism. The association of hyperhomocysteinemia and li pid abnormalities occurring in hypothyroidism may represent a dynamic ather ogenic state. Thyroid hormone failed to completely normalize t-Hcy. Potenti al 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.