Prenatal and postnatal development of the adrenal glands and adrenal steroid synthesis: effect on newborn screening for congenital adrenal hyperplasia
Abstract
The adrenal glands consist of the medulla producing adrenaline and noradrenaline and the adrenal cortex producing glucocorticoids, mineralocortocoids and androgens. The hormonal secretion of the adrenal cortex affects prenatal development of individual and maintains homeostasis of the organism during the postnatal period.
The initial structure of the adrenal cortex hormones is cholesterol which is metabolized with the participation of various enzymes to individual hormones. The enzyme defects cause diseases known as congenital adrenal hyperplasia.
Congenital adrenal hyperplasia (CAH) is a group of autosomale recessive disorders accompanied by impaired synthesis of mineralocorticoids, glucocorticoids and androgens. Clinical presentation is variable from severe, life-treating salt wasting crisis to mild, often unrecognized androgen overproduction.
Approximately 95% of CAH is caused by 21-hydroxylase deficiency. The neonatal screening was established to detect early and effectively the severe form of 21-hydroxylase deficiency.
The neonatal screening for CAH is based on the detection increased levels of 17-hydroxyprogesterone (17-OHP) from dried blood spots that is accumulated due to impaired activity of 21-hydroxylase. The level of 17-hydroxyprogesterone might be increased not only due to lower 21-hydroxylase activity, but also because of prematurity, hypoxia, sepsis of the newborns or the cross-reactivity with several other steroids.
All these aspects result in a low positive predictive value (1.6%). Improving the positive predictive value of the neonatal screening for CAH is possible by the other analytic tiers in the original dried blood spots with unclearly elevated 17-OHP.