Biochemical aspects of congenital adrenal hyperplasia

Abstract

The assay of 17 alpha-hydroxyprogesterone in blood spots on filter paper forms the basis of neonatal screening programmes to detect congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency. The blood concentrations of this hormone in the neonate varies with gestation age (term v preterm), age after birth, time of day and illness. Broad reference ranges for blood spot 17 alpha-hydroxyprogesterone concentrations are therefore quoted for healthy term infants and these ranges are not appropriate for the interpretation of values in preterm and sick newborns. There is a risk of a false-negative or of a false-positive diagnosis. Many of the above difficulties may result from variations in assay performance due to changes in the pattern of steroids produced by the adrenal gland which in turn relate to morphological changes in the adrenal cortex at this age. The purpose of this presentation is to define the complex steroid milieu of the newborn human and briefly to review the factors which determine the function of the adrenal gland, since these influence the extent to which an assay for this steroid needs to be evaluated before application to neonatal screening for CAH. The data to be presented derive from the capillary column gas chromatographic analysis (GC) of steroids in urine since this provides the best method to display the overall steroid production of the organism. The GC method has itself been refined so that CAH can now be reliably diagnosed using this method, but the information from this work will also be judged for its relevance to the problems encountered in the neonatal screening for CAH by blood spot analysis.