Gender disparities in screening for congenital hypothyroidism using thyroxine as a primary screen

in European Journal of Endocrinology
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Newborn screening for congenital hypothyroidism (CH) is based on testing for the markers thyroxine (T4) and/or thyroid-stimulating hormone (TSH). Diagnosis of CH is complicated because many factors affect the levels of these hormones including infant birth weight, prematurity and age at specimen collection. We investigated whether the sex of the newborn affected the levels of T4 and TSH and consequently the outcome of newborn screening.


In New York State, the Newborn Screening program initially tests all infants for T4 and any baby with a result in the lowest 10% is triaged for TSH screening. We analyzed data from 2008 to 2016 to determine mean and median T4 and TSH values and how these results correlate with the sex of infants who are reported as borderline, referred and confirmed with CH.


T4 and TSH concentrations in dried blood spots were measured using commercially available fluoroimmunoassays.


From 2008 to 2016, of the 2.4 million specimens tested for thyroxine, 51.5% were from male and 48.5% were from female infants. Male infants constituted 60% of specimens triaged for TSH testing, 64.9% of repeat requests and 59.6% of referrals, but only 49% of confirmed CH cases. The mean and median T4 values were lower (a difference of approximately 0.8–1.1 μg/dL each year) and the median TSH values were higher in male compared to female infants.


Natural differences in thyroid hormone levels in male and female infants leads to male infants being disproportionately represented in the false-positive category.


     European Society of Endocrinology

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    Current NYS screening algorithm for CH. *A repeat specimen is requested when a specimen collected on day of birth (DOB) is received but the specimen is nevertheless tested. If the TSH value of a DOB specimen is ≥150 μU/mL, the infant is immediately referred for CH. For a non-DOB specimen, an infant with a TSH value ≥100 μU/mL is immediately referred. T4, thyroxine; TSH, thyroid-stimulating hormone.

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    Yearly mean T4 values for male and female infants. (A) Yearly mean T4 values are lower in male than female infants (P < 0.0000001). A similar pattern was observed for yearly median T4 values (data not shown). Normal distribution curve for T4 values for male and female infants in 2014. (B) The normal distribution of T4 for male infants is represented by a black line, for female infants it is represented by a dashed black line. The normal distribution curve of T4 values for male infants are shifted to the left compared to female infants. This data represents 2014. A similar shift is seen for all other years from 2008 to 2016. Yearly median TSH values for male and female infants. (C) Yearly median TSH values are higher in male than female infants.



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