Hypothyroid women have persistently higher oxidative stress compared to healthy controls

Kamilla R Riis; Camilla B Larsen; Bjarke R Medici; Christian Z Jensen; Kristian H Winther; Emil L Larsen; Christina Ellervik; Jeppe L la Cour; Laszlo Hegedüs; Thomas H Brix; Henrik E Poulsen; Filip K Knop; Birte Nygaard; Steen J Bonnema

doi:10.1530/ETJ-23-0167

Hypothyroid women have persistently higher oxidative stress compared to healthy controls

Eur Thyroid J. 2023 Nov 3;12(6):e230167. doi: 10.1530/ETJ-23-0167. Print 2023 Dec 1.

Authors

Kamilla R Riis^{1

2}, Camilla B Larsen^{1

2}, Bjarke R Medici³, Christian Z Jensen³, Kristian H Winther¹, Emil L Larsen⁴, Christina Ellervik^{5

6

7}, Jeppe L la Cour³, Laszlo Hegedüs^{1

2}, Thomas H Brix¹, Henrik E Poulsen^{8

9

10}, Filip K Knop^{3

6

11

12}, Birte Nygaard^{3

6}, Steen J Bonnema^{1

2}

Affiliations

¹ Department of Endocrinology, Odense University Hospital, Odense, Denmark.
² Department of Clinical Research, University of Southern Denmark, Odense, Denmark.
³ Department of Medicine, Copenhagen University Hospital - Herlev and Gentofte, Denmark.
⁴ Department of Clinical Pharmacology, Bispebjerg-Frederiksberg Hospital, Copenhagen, Denmark.
⁵ Department of Laboratory Medicine, Boston Children's Hospital, Harvard Medical School, Boston, United States of America.
⁶ Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
⁷ Department of Data and Data Support, Region Zealand, Sorø, Denmark.
⁸ Department of Endocrinology, Copenhagen University Hospital, Bispebjerg-Frederiksberg Hospital, Denmark.
⁹ Faculty of Health Science, University of Copenhagen, Copenhagen, Denmark.
¹⁰ Department of Cardiology, University Hospital Nordsjælland, Hillerød, Denmark.
¹¹ Steno Diabetes Center Copenhagen, Herlev, Denmark.
¹² Center for Clinical Metabolic Research, Gentofte Hospital, University of Copenhagen, Hellerup, Denmark.

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) represents whole-body RNA and DNA oxidation, respectively. These biomarkers have only been explored sparsely in patients with thyroid disorders.

Methods: In 45 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. We also compared the excretion of 8-oxoGuo and 8-oxodG in the patients after restored euthyroidism with 18 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 at euthyroidism (95% CI: 1.53-1.83) (P = 0.39), while that of 8-oxodG was 1.28 nmol/mmol creatinine at baseline (95% CI: 1.14-1.44) and 1.32 nmol/mmol at euthyroidism (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 that of 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.

Keywords: 8-oxo-7,8-dihydro-2′-deoxyguanosine; 8-oxo-7,8-dihydroguanosine; 8-oxoGuo; 8-oxodG; hypothyroidism; oxidative stress.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

8-Hydroxy-2'-Deoxyguanosine / urine
Biomarkers / urine
Creatinine / urine
Female
Humans
Hypothyroidism* / drug therapy
Oxidative Stress / genetics
Thyroxine*

Substances

8-Hydroxy-2'-Deoxyguanosine
Thyroxine
Creatinine
Biomarkers