High TSH, Low FT4 Within Reference Ranges Linked to Cardiometabolic Risk in Youth

Blood sample tube with laboratory requisition form for thyroid hormone test
In children, low-normal thyroid function test results, even within reference ranges, may indicate increased cardiometabolic risk.

Higher thyroid-stimulating hormone (TSH) and lower free thyroxine (FT4) levels may be related to increased cardiometabolic risk factors in youth, even when within reference ranges, according to results of a population-based study published in Scientific Reports. Identifying and treating such risk factors may decrease the risk for cardiovascular disease and type 2 diabetes in adulthood.

A cohort of 250 euthyroid youths aged 10 to 18 years was selected using data from the 2015 Korea National Health and Nutrition Examination Survey (KNHANES). Researchers evaluated the differences in TSH and FT4 according to the presence of the 5 mandatory components of metabolic syndrome: reduced high-density lipoprotein cholesterol and elevated weight circumference, blood pressure, glucose level, and triglyceride level.

In unadjusted correlation analyses, TSH was positively correlated with glucose level (r=0.172; P =.006), hemoglobin A1c (HbA1c; r=0.149; P =.018), insulin (r=0.144; P =.023), homeostatic model assessment for insulin resistance (HOMA-IR; r=0.163; P =.010), and triglyceride level (r=0.155; P =.014). FT4 was negatively associated with waist circumference standard deviation score (r=-0.134; P =.035), insulin (r=-0.219; P <.001), and HOMA-IR (r =-0.211; P <.001).

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In multiple linear regression analysis adjusted for confounders, TSH was positively associated with glucose (β=1.179; P =.021), HbA1c (β=0.044; P =.039), and triglyceride level (β=8.158; P =.041). FT4 was negatively associated with serum fasting insulin (β=-5.884; P =.017) and HOMA-IR (β=-1.364; P =.023). Researchers also noted that youths without elevated glucose levels had lower adjusted mean TSH levels compared with youths with elevated glucose levels (2.16 mIU/L vs 3.88 mIU/L; P =.005).

Researchers acknowledged that puberty’s potential impact on thyroid hormone levels and insulin resistance may have influenced the study results. In addition, they did not have access to information about familial thyroid and cardiometabolic diseases.

“[H]igh TSH within the reference range was significantly associated with increases in serum fasting glucose, HbA1c and TG, whereas low FT4 within the reference range was related to increases in serum fasting insulin and an insulin resistance index,” the researchers wrote. “Our results suggest that low-normal thyroid function test results, even within the reference ranges, may be related to increased cardiometabolic risk factors.”

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Ma CG, Shim YS. Association of thyroid-stimulating hormone and thyroid hormones with cardiometabolic risk factors in euthyroid children and adolescents aged 10-18 years: a population-based study. Sci Rep. 2019;9(1):15476.