Cortisol in dried blood screening specimens from newborns with raised 17-hydroxyprogesterone and congenital adrenal hyperplasia.

Abstract

Screening for congenital adrenal hyperplasia (CAH) in newborns has become a routine part of many programmes by measuring levels of 17 alpha-hydroxyprogesterone (17-OHP) in the newborn filter-paper blood specimen. Unfortunately, raised levels of 17-OHP, which are largely the consequence of cross-reacting metabolites, are also found in low birth weight, premature and ill neonates. We speculated that differences in concentrations of cortisol in the newborn screening specimen would aid in distinguishing between CAH positive and CAH negative infants among those with raised levels of 17-OHP. Comparison of cortisol concentrations was made between newborns with CAH and those without but with raised 17-OHP levels. Newborn filter-paper blood specimens from 31 infants with transient 17-OHP elevations and 16 infants with confirmed CAH were analysed for cortisol. In addition, assay performance was validated by comparing cortisol values obtained from dried whole blood on filter-paper with the corresponding plasma from 31 adults and six neonates. Cortisol in filter-paper blood specimens was determined by adapting a commercial radioimmunoassay kit that had been designed for the determination of cortisol in serum. The mean cortisol level in the CAH negative group was significantly higher than the mean value in the group with documented CAH (means 1190 +/- 795 nmol/l vs 627 +/- 210 nmol/l; P < 0.01). However, approximately half of the CAH negative infants had cortisol values that overlapped those from the CAH positive group. There was no relationship between the magnitude of the 17-OHP elevation and cortisol concentrations. The measurements of cortisol in dried blood on filter-paper using a commercial radioimmunoassay kit has been shown to be reliable and simple to carry out. The level of cortisol in newborn blood specimens can be used to exclude some infants with elevated 17 alpha-hydroxyprogesterone levels from further testing for CAH. However, overlapping cortisol values between CAH positive and negative infants precludes the assay of cortisol from being used routinely as a reliable means of decision making.