Prenatal Diagnosis and Treatment of Congenital Adrenal Hyperplasia

Abstract

Congenital adrenal hyperplasia is a group of inherited disorders caused by an enzyme deficiency in steroid biosynthesis. The most common form of congenital adrenal hyperplasia is 21-hydroxylase deficiency, which in its severe form can cause genital ambiguity in females. Steroid 21-hydroxylase deficiency can be diagnosed in utero through molecular genetic analysis of fetal DNA. Prenatal treatment successfully reduces genital ambiguity, and the subsequent problems of sex misassignment and gender confusion. Data from current studies show that prenatal diagnosis and treatment are safe for the mother and the fetus. The evidence also suggests that it is safe over the long term, but all subjects exposed to dexamethasone treatment during embryonic and fetal life should have their physical, cognitive and emotional developments recorded.

Development of Adrenal Cortex Zonation

“…The most common form of CAH is the 21-hydroxylase deficiency ( CYP21A2 ), accounting for more than 95% of the cases 152 . More than 100 mutations have been described in this disease and a strong genotype-phenotype correlation is observed 153 . The classical form is characterized by the presence of virilization at birth with genital ambiguity on the female fetuses (due do androgen precursor accumulation) and severe adrenal insufficiency, that might be aggravated by mineralocorticoid deficiency in the salt-wasting forms 154 .…”

Prenatal Dexamethasone for Congenital Adrenal Hyperplasia

“…Because “the period during which the genitalia of a female fetus may become virilized begins only 6 [weeks] after conception, treatment must be instituted as soon as the woman knows she is pregnant” (Speiser et al 2010a, 4137; cf. Nimkarn and New 2007). Although this intervention is sometimes termed “low-dose therapy” (New 2010c), researchers estimate that “the effective glucocorticoid doses reaching the fetus are 60–100 times physiologic” (Miller 2008, 17), meaning this intervention exposes the developing fetus to 60 to 100 times the normal level of glucocorticoids.…”

Congenital Adrenal Hyperplasia

“…130 Under normal circumstances, the human fetal adrenal cortex does not synthesize significant quantities of cortisol during early pregnancy. 131 The fetus is protected from maternal glucocorticoids by placental expression of the 11β-hydroxysteroid dehydrogenase type 2 (HSD11B2) enzyme that inactivates maternal cortisol by converting it to inactive cortisone.…”