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Rethinking Normal Thyroid-Stimulating Hormone (TSH): Stroke Risk and Metabolic Implications in High-Risk
Lia Cals1, Maria Zanella2, Simone Matsuda1
1Endocrinology, Diabetes, and Metabolism, Universidade Federal de Medicina de São Paulo, São Paulo, BRA.
Abstract:
Objective This study aimed to evaluate whether variations in normal-range thyroid-stimulating hormone (TSH) levels affect cardiovascular outcomes in patients at high cardiovascular (CV) risk. Methods A cross-sectional study was conducted involving 463 middle-aged euthyroid patients (354 women, 109 men) under treatment for hypertension and dyslipidemia (TSH range: 0.5-5.2 mIU/L). Patients were grouped by TSH tertiles: lower (0.5-1.3 mIU/L), middle (>1.3-2.16 mIU/L), and upper (>2.16-5.2 mIU/L). For statistical analysis, we compared individuals with TSH ≤2.16 mIU/L (n=310) versus those with TSH >2.16 mIU/L (n=153). Results Anthropometric and laboratory parameters were comparable between groups, except for higher triglycerides (Tg) (151.9 ±74.9 vs. 136.0 ±72.7 mg/dL) and Tg-to-high-density lipoprotein (HDL) ratio (3.17 ±2.05 vs. 2.92 ±2.07) in those with upper-normal TSH (p<0.05). Positive correlations emerged between TSH and BMI (r=0.099, p=0.033) as well as between TSH and the Tg-to-HDL ratio (r=0.149, p=0.001). Interestingly, stroke prevalence was higher in patients whose TSH levels were in the lower-normal range (6.1% vs. 2.0%, p=0.047). Multivariate regression, adjusting for age, sex, BMI, and Tg-to-HDL ratio, showed that patients with lower-normal TSH were five times more likely to experience stroke (odds ratio (OR): 5.08; 95% confidence interval (CI): 1.15-22.25; p=0.031). Conclusions Within normal TSH ranges, lower-normal TSH levels were associated with a higher risk of stroke, while upper-normal TSH was linked to higher Tg levels and insulin resistance markers. These findings underscore the importance of carefully evaluating TSH levels in high-risk patients. Further prospective studies are needed to confirm these results and elucidate underlying mechanisms.
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