Hypothyroid women have persistently higher oxidative stress compared to healthy controls

Abstract

Objective: Some studies suggest that hypothyroidism is associated with increased oxidative stress. Urinary excretion of 8-oxo-7,8-dihydroguanosine (8-oxoGuo) and 8-oxo-7,8-dihydro-2’-deoxyguanosine (8-oxodG) represent whole-body RNA and DNA oxidation, respectively. These biomarkers have only been explored sparsely in patients with thyroid disorders. Methods: In forty-five Danish women with newly diagnosed hypothyroidism, we compared 8-oxoGuo and 8-oxodG before or shortly after initiating levothyroxine with the excretion rates at euthyroidism. Also, we compared the excretion of 8-oxoGuo and 8-oxodG in the patients after restored euthyroidism with eighteen healthy control subjects. Results: Compared with baseline, none of the biomarkers changed significantly in the patients after becoming euthyroid. The geometric mean of 8-oxoGuo was 1.63 (95%CI:1.49-1.78) nmol/mmol creatinine at baseline and 1.67 nmol/mmol (95%CI:1.53-1.83) at euthyroidism (p=0.39), while 8-oxodG was 1.28 nmol/mmol creatinine (95%CI:1.14-1.44) and 1.32 nmol/mmol (95%CI:1.18-1.48), respectively (p=0.47). The relative mean differences were 0.97 (95%CI:0.91-1.04) for 8-oxoGuo and 0.97 (95%CI:0.88-1.06) for 8-oxodG. At baseline, multiple linear regression revealed a positive association between free thyroxine and both biomarkers (8-oxoGuo, p<0.001; 8-oxodG, p=0.04). Furthermore, 8-oxoGuo was positively associated with age (p=0.04) and negatively associated with thyrotropin (p=0.02). In the control group, the geometric mean of 8-oxoGuo was 1.23 nmol/mmol creatinine (95%CI:1.07-1.42), while 8-oxodG was 1.04 nmol/mmol creatinine (95%CI:0.88-1.23). Thus, compared with control subjects, euthyroid patients showed a significantly higher level of both 8-oxoGuo (p<0.001) and 8-oxodG (p=0.03). Conclusion: In hypothyroid women, no significant effect of levothyroxine treatment on the oxidative stress biomarkers 8-oxoGuo and 8-oxodG could be demonstrated. However, the excretion of these biomarkers was significantly higher than in healthy controls.