Endocrine Abstracts

Background: Increased oxidative stress has been linked to both hypo- and hyperthyroidism. Whole-body oxidative stress can be estimated by the oxidized guanine nucleosides, 8-oxo-7.8-dihydroguanosine (8-oxoGuo) and 8-oxo-7.8-dihydro-2’-deoxyguanosine (8-oxodG), derived from RNA and DNA, respectively. These biomarkers have been associated with increased morbidity and mortality in several diseases but are not well explored in humans with thyroid disorders.

Methods: We measured urinary excretion of 8-oxoGuo and 8-oxodG in 51 hyperthyroid patients (toxic nodular goiter (TNG), n = 30; Graves’ disease (GD), n = 21) before, or shortly after, initiation of therapy and when stable euthyroidism had been achieved for at least 12 months. Patients with TNG were older (mean: 59 ± 12 s.d. years) than those with GD (50 ± 8 years). Mean follow-up time was 17.2 ± 4.6 and 22.9 ± 8.9 months for TNG and GD, respectively. All patients with TNG were treated with radioiodine, except for one who underwent thyroidectomy. GD patients were treated with methimazole andtwo of whom also received radioiodine.

Results: Both oxidative stress markers correlated positively with age (8-oxoGuo: P < 0.001; 8-oxodG: P = 0.003). After adjustment, the baseline urinary excretions correlated with the severity of the disease, reflected by the plasma levels ofthyroxine (8-oxoGuo: P = 0.002; 8-oxodG: P = 0.021), and were significantly higher in GD than in TNG (P = 0.001 for both biomarkers). Treatment significantly affected the excretions of the oxidative stress markers. In TNG, 8-oxoGuo decreased from geometric mean (GM) 2.11 nmol/mmol (95% CI : 1.85–2.39) to 1.91 nmol/mmol (95% CI : 1.67–2.19), P = 0.001, while 8-oxodG decreased from 1.65 nmol/mmol (95% CI : 1.41–1.93) to 1.48 nmol/mmol (95% CI : 1.27–1.74), P = 0.026. In GD, 8-oxoGuo decreased from 2.25 nmol/mmol (95% CI : 1.95–2.59) to 1.79 nmol/mmol (95% CI : 1.63–1.97), P = 0.0003, while 8-oxodG decreased from 2.02 nmol/mmol (95% CI : 1.73–2.38) to 1.54 nmol/mmol (95% CI : 1.63–1.97), P = 0.001. When euthyroid, no between-group differences were found.

Conclusion: Treatment of hyperthyroidism significantly decreased the systemic oxidative stress load by 10–25%, as measured by the urinary excretion of nucleic acid metabolites. The higher values in patients with GD could be due to the more severe hyperthyroidism seen in this condition. Our findings may signify a key factor, explaining the higher morbidity and mortality linked to patients with hyperthyroid diseases, as shown in observational studies.