Identification and characterization of two groups of congenital hypothyroid infants: implications for newborn screening

A retrospective analysis of 400 newborns diagnosed with congenital primary hypothyroidism between 1983 and 1987 was conducted. Two distinct groups of cases were identified and characterized based on their newborn screening TSH value. The two groups are separated at a TSH concentration of 50 mU/1 of serum by a normal probability plot. This finding is in agreement with the 1993 recommendation from the American Academy of Pediatrics that infants with a low T4 level and a TSH concentration greater than 40 mU/1 be considered to have primary hypothyroidism until proven otherwise. The group of infants with TSH less than 50 mU/1 have a higher proportion of males and low birthweight infants. For this group, T4 increases with increasing TSH. We find that screening TSH, T4, and birthweight are predictive of follow-up serum TSH level for the cases with TSH > 50 mU/1 but not for cases with TSH < 50 mU/1. An optimal rule for selecting screening cutoff levels is presented based on only T4, TSH and their interaction. Adjustments for sex, birthweight or age at which sample was taken did not aid in distinguishing cases from controls for newborns whose age of sample is 2 days or greater.