Treatment of Hyperthyroidism Reduces Systemic Oxidative Stress, as Measured by Markers of RNA and DNA Damage.

Abstract

BACKGROUND:

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.

OBJECTIVE:

We aimed to determine whether treatment of hyperthyroid patients affects the levels of these oxidative stress markers.

METHODS:

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.

RESULTS:

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.

CONCLUSION:

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.

• Authors: Camilla B Larsen, Kamilla R Riis, Kristian H Winther, Emil L Larsen, Christina Ellervik, Laszlo Hegedüs, Thomas H Brix, Henrik E Poulsen, Steen J Bonnema
• Journal: The Journal of clinical endocrinology and metabolism (J Clin Endocrinol Metab) Vol. 106 Issue 7 Pg. e2512-e2520 (06 16 2021) ISSN: 1945-7197 [Electronic] United States
• PMID: 33901280 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © The Author(s) 2021. Published by Oxford University Press on behalf of the Endocrine Society. All rights reserved. For permissions, please e-mail: [email protected].

Chemical References

• Antithyroid Agents
• Biomarkers
• Guanosine
• 8-hydroxyguanosine
• 8-Hydroxy-2'-Deoxyguanosine
• Thyroxine

Topics

• 8-Hydroxy-2'-Deoxyguanosine (urine)
• Adult
• Aged
• Aged, 80 and over
• Antithyroid Agents (therapeutic use)
• Biomarkers (urine)
• DNA Damage
• Female
• Guanosine (analogs & derivatives, urine)
• Humans
• Hyperthyroidism (blood, drug therapy, urine)
• Middle Aged
• Oxidative Stress
• Prospective Studies
• Thyroxine (blood)
• Treatment Outcome
• Young Adult