Objective: To evaluate whether subclinical hypothyroidism is associated with hyperhomocysteinemia, in an attempt to determine whether hyperhomocysteinemia may explain the observed increased risk of coronary artery disease in patients with subclinical hypothyroidism, as has been shown in patients with overt hypothyroidism.
Methods: We prospectively enrolled consecutive patients with newly diagnosed subclinical hypothyroidism and a parallel group of euthyroid control subjects in this study. Subclinical hypothyroidism was defined as high thyrotropin and normal free thyroxine levels. Fasting plasma total homocysteine, thyrotropin, and free thyroxine levels were measured in all participants, and persistent subclinical hypothyroidism was confirmed at least once.
Results: Forty-seven patients (42 women and 5 men; mean age, 38 +/- 15 years) with subclinical hypothyroidism and 50 control subjects (46 women and 4 men; mean age, 34 +/- 10 years) were enrolled in the study. The manufacturer's reference range for the total homocysteine assay was 5 to 15 micromol/L, and we defined our own reference range as 3.9 to 10.8 micromol/L. The mean values (+/-SE) for total homocysteine in patients and control subjects were 7.44 +/- 0.5 micromol/L and 7.22 +/- 0.2 micromol/L, respectively (P = 0.68).
Conclusion: In this study, we found no association between subclinical hypothyroidism and hyperhomocysteinemia. Other contributing factors, such as associated hyperlipidemia, may explain the observed increased risk of coronary artery disease in patients with subclinical hypothyroidism.