BMI, ethnicity independent predictors of TSH reference values for children
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Thyroid-stimulating hormone reference values for children are affected by BMI and ethnicity, and reference values should be individualized accordingly to improve clinical decision-making and reduce unnecessary treatments, study data show.
“Thyroid hormones are of crucial importance during childhood and adolescence, affecting all aspects of growth and development,” Joseph Meyerovitch MD, professor at Sackler Faculty of Medicine of Tel Aviv University in Israel, told Healio. “Primary care physicians tend to evaluate thyroid function as a screening test in children and adolescents presenting with a wide range of nonspecific complaints. The most sensitive index of thyroid function in the absence of a hypothalamic-pituitary disease is serum TSH. Using a unified upper reference limit that does not consider the anticipated TSH elevation caused by excessive weight would misclassify these children as having thyroid disease, leading to further unnecessary thyroid testing and even treatment.”
In an observational study, Meyerovitch and colleagues used the Clalit Health Services database to analyze data of 75,549 healthy children aged at least 5 years (mean age, 12 years; 83% Jewish; 17% Israeli Arab) who had undergone at least one thyroid function test between December 2012 and December 2014. All children had free thyroxine (FT4) levels in the normal range and TSH levels below 10 mIU/L. Researchers used logistic regression analyses to examine the variables affecting the 2.5 and 97.5 percentiles, thereby refining the TSH reference interval.
Researchers found that the 2.5 percentile was affected by sex (P < .01), as well as overweight status (P < .005) and obesity (P < .001), whereas the 97.5 percentile was affected by ethnic origin and elevated BMI (P < .001 for both). Age was not associated with TSH levels.
“Our model implies that the decline in TSH levels with age might be due to changes in BMI, gender and ethnicity, but not to age itself,” the researchers wrote. “These results are in line with other studies showing that anthropometric features and ethnicity might be the major determinants in the variation of TSH and FT4 throughout a child’s life rather than age itself.”
Comparing the current and suggested reference intervals for TSH levels, researchers found that 25.1% of the children with TSH levels above the reference limit according to current values are in the reference interval according to the suggested values, whereas 2.3% of the children in the reference interval according to the current values are below the reference limit according to the suggested values.
“The traditional approach of ‘one size fits all’ leads to misclassification of millions of children with either raised or decreased TSH, governing the additional unnecessary and costly evaluation of the thyroid, and occasionally unwarranted treatment,” the researchers wrote. “It is therefore of crucial importance to provide clinicians with population-specific thyroid function test reference intervals. Our study of data from a very large pediatric cohort in Israel, which showed that ethnicity and BMI were the major determinants of TSH reference values, has permitted the establishment of more accurate, personalized thyroid function references values for this population, and suggests the importance of taking such factors into account when dealing with other populations elsewhere.”
For more information:
Joseph Meyerovitch MD, can be reached at josephm1@outlook.com.
Perspective
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John P. Walsh, MBBS, FRACP, PhD
This study confirms previous studies demonstrating that TSH levels show minor differences between ethnic groups, and that obesity is associated with higher TSH levels. The authors advocate the use of ethnicity- and BMI-adjusted reference intervals for TSH; however, in practice this would be very difficult, as ethnicity and BMI data are rarely available to laboratories performing routine testing. This study will be useful to clinicians who interpret thyroid function tests, providing further reassurance that minor deviations in TSH from the reference range are rarely important, and that mild elevations in TSH can be caused by obesity, rather than the other way around.
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