Endocrine Abstracts

Background: Hyperthyroidism as well as hypothyroidism have been associated with oxidative stress, caused by an imbalance between pro-oxidants and antioxidants. Oxidative stress may damage the genomic apparatus and other cellular structures. Urinary excretion of 8-oxo-7.8-dihydroguanosine (8-oxoGuo) and 8-oxo-7.8-dihydro-2’-deoxyguanosine (8-oxodG), respectively, represent global RNA and DNA oxidation, thus reflecting oxidatively generated modification of nucleic acids in the entire organism. While these biomarkers have been associated with increased morbidity and mortality in various diseases, they have only sparsely been explored in patients with thyroid disorders.

Method: Twenty-eight hypothyroid women (overt: n = 6; subclinical: n = 22) were included in a prospective cohort study. Mean age was 48.4 ± 10.8(S.D.) years at diagnosis. Urinary excretion of 8-oxoGuo and 8-oxodG, corrected for creatinine, were measured shortly after initiation of levothyroxine (LT4) supplementation [mean 38 ± 26 days between start of treatment and first study visit], and after a minimum 12 months of stable euthyroidism.

Results: Before treatment, TSH was 9.40 ± 4.97 mIU/l and total T4 was 75.0 ± 18.4 nmol/l. Mean follow-up time was 604 ± 251 days. When euthyroid, the mean LT4 dose was 112 ± 36 µg, and TSH had decreased to 2.48 ± 2.08 mIU/l. As 8-oxoGuo and 8-oxodG were not normally distributed, a logarithmic transformation was applied. Compared to baseline, none of the biomarkers changed significantly after 12 months of euthyroidism. 8-oxoGuo: geometric mean (GM) 1.82 (95% CI: 1.62–2.03) nmol/mmol creatinine at baseline and GM 1.88 nmol/mmol creatinine (95% CI: 1.67–2.11) at euthyroidism, P = 0.51. 8-oxodG: GM 1.37 nmol/mmol creatinine (95% CI: 1.15–1.64) at baseline and GM 1.45 nmol/mmol creatinine (95% CI: 1.23–1.70) at euthyroidism, P = 0.44.

Conclusions: To the best of our knowledge this is the first study to evaluate the impact of LT4 treatment in hypothyroid patients on the excretion of the nucleic acid metabolites 8-oxoGuo and 8-oxodG. We found no significant effect of restoration of euthyroidism on these biomarkers of whole-body oxidative stress. However, the negative finding may be explained by most of our patients having subclinical rather than overt hypothyroidism. Thus, larger studies of patients with more severe thyroid failure are needed to further explore the relationship between hypothyroidism, its treatment, and whole-body oxidative stress.