Prenatal and Early Postnatal Treatment of Congenital Adrenal Hyperplasia

Abstract

Congenital adrenal hyperplasia is a group of monogenic autosomal recessive disorders due to an enzyme deficiency in steroid biosynthesis. The most frequent form of congenital adrenal hyperplasia is 21-hydroxylase (21-OH) deficiency, which in its severe form can cause ambiguous genitalia in the female patient. Recent advances in molecular genetic analysis allow for prenatal diagnosis and treatment of at-risk fetuses. The objective of prenatal diagnosis and treatment of 21-OH deficiency is the prevention of prenatal virilization in affected female infants, reducing the risks of sex misassignment and gender confusion, and the need for corrective genital surgery. Prenatal treatment of 21-OH deficiency is effective in reducing genital ambiguity, and short-term outcome studies of children exposed to dexamethasone in utero indicate no significant adverse effects. However, more long-term studies of treated versus untreated pregnancies are warranted to monitor the safety of treatment and enhance our understanding of the effects of prenatal steroid exposure to the human brain. In the first year of life, optimization of medical treatment in salt-wasting patients is achieved by combining the lowest dose of glucocorticoid able to suppress androgen secretion with the normalization of sodium balance by giving appropriate sodium chloride supplementation.

Ambiguous External Genitalia in Childhood in Port Harcourt, Nigeria

“…In view of this, many affected children required mini-laparotomy for direct visualization and biopsy of gonads, this approach to confirm or assign gender was adopted and found helpful by earlier authors in low resource regions [12,14,20]. The direct visualization of internal genitalia in other cases is also important to ascertain their normalcy for the purpose of sexual functions and reproduction [21,22]. Though the acceptance of minilaparatomy by parents have posed a great problem which accounted for the low rate in this study, however in the study in Ile Ife, [14] in Western Nigeria laparotomy was the major tool of diagnosis and helped to determine sex of rearing and possibly determine the appropriate genital reconstruction surgery.…”

“…Although the lesions are benign, early detection is important so as to assign the correct gender at birth and prevent avoidable complications which may occur later in life. Early treatment in most cases of ambiguous external genitalia is associated with little or no sequalae [11].…”

Fetal Laboratory Medicine: On the Frontier of Maternal–Fetal Medicine

“…The most common etiology is 21-hydroxylase (21-OH) deficiency. The goal of prenatal diagnosis and treatment and of 21-OH deficiency is prevention of prenatal virilization in affected female fetuses, and avoidance of consequences such as risk of gender misassignment, gender confusion, and indications for possible corrective genital surgery (37 ). Early diagnosis (before the 15th gestational week) is desirable.…”

“…Early diagnosis (before the 15th gestational week) is desirable. Genotyping for the responsible CYP21 (cytochrome P450, family 21, subfamily A, polypeptide 2) 3 gene can be performed from chorionic villi sampled at 10-11 weeks gestation, although technical factors can lead to diagnostic mishaps (37). Amniotic 17-hydroxyprogesterone is the diagnostic biochemical marker for 21-hydroxylase deficiency, is unaffected by sex, and variation with gestational age is not significant (38 ).…”

Learned lessons, changing practice and cutting-edge research: how to reduce scientific uncertainty in neonatology pursuing the triple aim

“…Prenatal endocrine analysis is another area of fetal diagnostic impact. The goal of prenatal diagnosis and treatment of 21-OH deficiency, originating congenital adrenal hyperplasias, is prevention of prenatal virilization in affected female fetuses, and avoidance of consequences such as risk of gender misassignment, gender confusion, and indications for possible corrective genital surgery [10]. Early diagnosis, preferably before the 15th gestational week, is desirable.…”