Department of Endocrinology, Odense University Hospital, Denmark.
Department of Clinical Research, University of Southern Denmark, Denmark.
J Clin Endocrinol Metab. 2021 Jun 16;106(7):e2512-e2520. doi: 10.1210/clinem/dgab273.
Whole-body oxidative stress can be estimated by the urine excretion of oxidized guanosine species, 8-oxo-7,8-dihydroguanosine (8-oxoGuo) and 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodG), derived from RNA and DNA, respectively. These oxidative stress markers are not well explored in thyroid disorders.
We aimed to determine whether treatment of hyperthyroid patients affects the levels of these oxidative stress markers.
Urinary excretion of 8-oxoGuo and 8-oxodG was measured 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.
Adjusting for age, the baseline urinary excretion of oxidative stress markers correlated positively with plasma thyroxine (8-oxoGuo, P = 0.002; 8-oxodG, P = 0.021) and was significantly higher in GD than in TNG patients (P = 0.001 for both oxidative stress markers). Restoration of euthyroidism significantly affected the excretion of the oxidative stress markers. In TNG, 8-oxoGuo decreased from geometric mean 2.11 nmol/mmol creatinine (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, 1.31-1.81; P = 0.001). In the euthyroid state, there were no differences between groups.
Restoration of euthyroidism in patients with hyperthyroidism significantly decreased the systemic oxidative stress load by 10% to 25%. Our findings may help to explain the higher morbidity and mortality linked to hyperthyroid diseases, as shown in observational studies.
全身氧化应激可通过尿中氧化鸟嘌呤核苷的排泄来评估，分别来自 RNA 和 DNA 的 8-氧代-7,8-二氢鸟苷（8-oxoGuo）和 8-氧代-7,8-二氢-2'-脱氧鸟苷（8-oxodG）。这些氧化应激标志物在甲状腺疾病中尚未得到充分研究。
我们旨在确定治疗甲状腺功能亢进症患者是否会影响这些氧化应激标志物的水平。
测量了 51 例甲状腺功能亢进症患者（毒性结节性甲状腺肿[TNG]，n=30；格雷夫斯病[GD]，n=21）在开始治疗前或治疗后不久以及稳定的甲状腺功能正常状态至少 12 个月时的尿 8-oxoGuo 和 8-oxodG 排泄量。
调整年龄后，氧化应激标志物的基线尿排泄量与血浆甲状腺素呈正相关（8-oxoGuo，P=0.002；8-oxodG，P=0.021），并且 GD 患者的排泄量明显高于 TNG 患者（两种氧化应激标志物均为 P=0.001）。甲状腺功能正常状态的恢复显著影响了氧化应激标志物的排泄。在 TNG 中，8-oxoGuo 从几何均数 2.11 nmol/mmol 肌酐（95%CI，1.85-2.39）降至 1.91 nmol/mmol（95%CI，1.67-2.19；P=0.001），而 8-oxodG 从 1.65 nmol/mmol（95%CI，1.41-1.93）降至 1.48 nmol/mmol（95%CI，1.27-1.74；P=0.026）。在 GD 中，8-oxoGuo 从 2.25 nmol/mmol（95%CI，1.95-2.59）降至 1.79 nmol/mmol（95%CI，1.63-1.97；P=0.0003），而 8-oxodG 从 2.02 nmol/mmol（95%CI，1.73-2.38）降至 1.54 nmol/mmol（95%CI，1.31-1.81；P=0.001）。在甲状腺功能正常状态下，两组之间无差异。
甲状腺功能亢进症患者甲状腺功能正常状态的恢复使全身氧化应激负荷降低了 10%至 25%。我们的发现可能有助于解释观察性研究中与甲状腺功能亢进症相关的更高发病率和死亡率。
