Association of Serum Uric Acid with Thyroid Function in Health Check-up Participants
Thyroid hormones (THs) play critical roles in various physiological processes, including development, growth, metabolism, and reproduction. Recent attention has been drawn to THs due to their association with metabolic diseases, as they enhance energy metabolism in the body. Research has focused on the roles of THs in glucose oxidation, oxidative phosphorylation, fat degradation, and other metabolic activities. Additionally, TH mimetics have been proposed for managing diabetes and obesity. Understanding the population-based distribution of thyroid dysfunction is crucial, as it is a potential risk factor for cardiovascular disease, hypercholesterolemia, arrhythmia, osteoporosis, and neuropsychiatric disorders. While the adverse effects of thyroid dysfunction on the metabolic system are well-recognized, the association between TH levels and hyperuricemia risk in euthyroid individuals remains unclear.
Uric acid (UA) is the final oxidation product of purine metabolism in the human body, exhibiting both pro-oxidant and antioxidant activities. Although UA does not directly contribute to metabolic syndrome, elevated serum UA levels are commonly observed in patients with metabolic disorders. Serum UA levels are considered an independent predictor of metabolic syndrome risk. This has led to the suggestion that UA might be related to thyroid function. Previous studies have explored this association in patients with overt thyroid dysfunction, but the relationship between UA and thyroid function in healthy individuals remains unclear. This cross-sectional study aimed to evaluate the association between serum UA levels and thyroid function in healthy Chinese individuals.
The study included 1186 Chinese adults (736 men and 450 women) who underwent health check-ups at Huadong Hospital Affiliated to Fudan University in Shanghai, China, between January 1, 2010, and July 31, 2018. Participants were divided into different UA groups based on their serum UA levels. For men and postmenopausal women, the groups were MG1: UA < 5 mg/dL; MG2: 5 mg/dL ≤ UA < 7 mg/dL; and MG3: UA ≥ 7 mg/dL. For premenopausal women, the groups were FG1: UA < 4 mg/dL; FG2: 4 mg/dL ≤ UA < 6 mg/dL; and FG3: UA ≥ 6 mg/dL. Clinical and thyroid hormone levels were compared across these groups. Natural cubic spline regression and Pearson correlation analysis were used to investigate the correlation between UA and thyroid hormones.
After adjusting for confounding factors, low levels of UA (UA < 5.30 mg/dL for men and UA < 4.05 mg/dL for women) were negatively correlated with free triiodothyronine (FT3) in both men and women. In women, UA levels between 4.83 and 6.06 mg/dL were associated with a protective effect on FT3, while in men, UA levels between 6.39 and 7.09 mg/dL had a similar protective effect. FT3 levels were significantly lower in the low-range UA groups compared to the mid-range and high-range UA groups in both men and women. These findings suggest that low serum UA levels may serve as a risk factor for poor thyroid function in the Chinese Han population.
The study also examined the relationship between UA and other clinical parameters. In men, UA was positively correlated with triglycerides (TG) and body mass index (BMI) but negatively correlated with estimated glomerular filtration rate (eGFR) and age. In women, UA was positively associated with age, BMI, fasting blood glucose (FBG), and TG, but inversely related to eGFR. These parameters were identified as confounding factors in the relationship between UA and thyroid function.
Natural cubic spline regression analysis revealed that in men, UA had a negative effect on FT3 when levels were below 5.30 mg/dL, and this negative effect increased as UA levels decreased. Conversely, UA had a positive effect on FT3 in the range of 6.39 to 7.09 mg/dL. In women, UA negatively affected FT3 at levels below 4.05 mg/dL, with the negative effect increasing as UA levels decreased. UA had a positive effect on FT3 in the range of 4.83 to 6.06 mg/dL. In postmenopausal women, UA negatively affected FT3 at levels below 4.02 mg/dL, with a positive effect observed in the range of 4.75 to 5.76 mg/dL.
The study’s findings provide epidemiological evidence supporting the negative correlation between low UA levels and FT3 in the Chinese Han population. This suggests that reduced UA levels may serve as a risk factor for predicting poor thyroid function. The study also highlights the potential protective effects of moderate UA levels on thyroid function, particularly in the ranges of 4.83 to 6.06 mg/dL for women and 6.39 to 7.09 mg/dL for men.
Several factors may explain the observed relationship between UA and thyroid function. Thyroid hormones are associated with oxidative stress (OS) and antioxidant status, as they influence mitochondrial respiration and basal metabolism. Changes in TH levels can regulate cellular OS in vivo. Low levels of free radicals are generated in hypothyroidism due to suppressed metabolism, while hyperthyroidism increases OS. UA, as a potent antioxidant, may influence TH levels through its ability to scavenge free radicals. Moderate elevations in plasma UA levels may protect thyroid function by reducing OS.
BMI and renal function are also important considerations in the relationship between UA and thyroid function. BMI has been shown to correlate with thyroid function, with higher BMI associated with increased thyroid cancer risk. In this study, low UA levels remained inversely related to FT3 after adjusting for BMI, suggesting that BMI may not significantly influence the observed relationship. Similarly, THs are associated with renal dysfunction, with higher FT4 levels linked to increased chronic kidney disease risk. The study adjusted for eGFR, confirming that the relationship between UA and FT3 is independent of renal function.
The study has several strengths, including the separate analysis of data from men and women, rigorous exclusion criteria to minimize bias, and the identification of different effects of low and high UA levels on FT3. However, there are limitations to consider. The cross-sectional nature of the study precludes the establishment of causal relationships between UA and thyroid dysfunction. The study population consisted of individuals visiting a physical examination center, which may limit the generalizability of the findings. Additionally, smoking history, which can influence thyroid function, was not recorded.
In conclusion, this study demonstrates that low serum UA levels are negatively correlated with FT3 in both men and women, while moderate UA levels may protect thyroid function. These findings suggest that UA, as a natural antioxidant, may serve as a risk factor for thyroid disease at low levels. Further research is needed to explore the underlying mechanisms and to determine the optimal UA target levels for the prevention and treatment of thyroid dysfunction.
doi.org/10.1097/CM9.0000000000000840
Was this helpful?
0 / 0