Significant evolution of adrenal steroid production occurs over the first days and months of life as the adrenal cortex plays a major role in the newborn infant’s postnatal adaptation. New, in Avery's Diseases of the Newborn (Ninth Edition), 2012 Assessing Adrenal Function in the Newborn However, because 21-hydroxylase deficiency is variable depending on the nature of the genetic mutation, and because minimal activity is required in the mineralocorticoid pathway, salt loss associated with mineralocorticoid deficiency usually only results in the more severe form of the condition ( New et al., 2013c). The accumulation of 17-OHP due to chronic elevation of ACTH leads to excess production of adrenal androgens which are converted to testosterone in the liver. Therefore, in 21OHD, the inhibited cortisol production leads to increased ACTH production, which in turn stimulates excessive synthesis of adrenal products in pathways unimpaired by enzymatic deficiency as well as buildup of precursors, mainly 17-OHP in pathways blocked by the enzymatic deficiency ( Azziz et al., 1990 White and Speiser, 2000). This HPA feedback system is mediated via the circulating level of plasma cortisol in negative feedback on CRH and ACTH.

Hypothalamic corticotropin-releasing hormone (CRH) regulates the release of adrenocorticotropic hormone (ACTH) from the pituitary, thereby activating the HPA axis and glucocorticoid release.

Within the adrenal, the zona glomerulosa, zona fasciculata, and zona reticularis act as separate glands producing glucocorticoids, mineralocorticoids, and sex hormones ( Ganong, 1963 Guillemin and Schally, 1963), as depicted in Figure 1. Adrenal steroid production occurs in three major pathways within the hypothalamic–pituitary–adrenal (HPA) axis.

Adrenal production