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Recent advances in the diagnosis and management of congenital adrenal hyperplasia due to 21-hydroxylase deficiency.
Hum Reprod Update. 2004 Nov-Dec; 10(6):469-85.HR

Abstract

Congenital adrenal hyperplasias (CAH) are inherited defects of cortisol biosynthesis. More than 90% of CAH are caused by 21-hydroxylase deficiency (21-OHD), found in 1:10 000 to 1:15 000 live births. Females with 'classical' 21-OHD, being exposed to excess androgens prenatally, are born with virilized external genitalia. Potentially lethal adrenal insufficiency is characteristic of two-thirds to three-quarters of patients with the classical salt wasting (SW) form of 21-OHD. Non-SW 21-OHD may be diagnosed on genital ambiguity in affected females, and/or later on the occurrence of androgen excess in both sexes. Non-classical 21-OHD, detected in > or =1:100 of certain populations, may present as precocious pubarche in children or polycystic ovarian syndrome in young women. 21-OHD is caused by mutations in the CYP21 gene encoding the steroid 21-hydroxylase enzyme. More than 90% of these mutations result from intergenic recombination between CYP21 and the closely linked CYP21P pseudogene. The degree to which each mutation compromises enzymatic activity is strongly correlated with the clinical severity of the disorder. This close association between genotype and phenotype makes it possible to predict clinical outcome in affected subjects. The risk of SW and prenatal virilization can be estimated, and overtreatment can be avoided in mildly affected cases. Glucocorticoid and mineralocorticoid replacement therapies are the mainstays of treatment, but additional therapies are being developed. A first trimester prenatal diagnosis should be proposed in families in whom molecular studies have been performed previously. The state of heterozygotism can be predicted by hormonal testing and confirmed by molecular studies. Prenatal diagnosis by direct mutation detection in previously genotyped families permits prenatal treatment of affected females in order to avoid or minimize genital virilization. Neonatal screening by hormonal methods identifies affected children before SW crises develop, reducing mortality in this disorder.

Authors+Show Affiliations

Biologie Endocrinienne et Moléculaire, EA 3739 Hôpital Debrousse, 29 rue Soeur Bouvier, 69322 Lyon Cedex 05, France. forest@lyon.inserm.fr

Pub Type(s)

Journal Article
Review

Language

eng

PubMed ID

15514016

Citation

Forest, Maguelone G.. "Recent Advances in the Diagnosis and Management of Congenital Adrenal Hyperplasia Due to 21-hydroxylase Deficiency." Human Reproduction Update, vol. 10, no. 6, 2004, pp. 469-85.
Forest MG. Recent advances in the diagnosis and management of congenital adrenal hyperplasia due to 21-hydroxylase deficiency. Hum Reprod Update. 2004;10(6):469-85.
Forest, M. G. (2004). Recent advances in the diagnosis and management of congenital adrenal hyperplasia due to 21-hydroxylase deficiency. Human Reproduction Update, 10(6), 469-85.
Forest MG. Recent Advances in the Diagnosis and Management of Congenital Adrenal Hyperplasia Due to 21-hydroxylase Deficiency. Hum Reprod Update. 2004 Nov-Dec;10(6):469-85. PubMed PMID: 15514016.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Recent advances in the diagnosis and management of congenital adrenal hyperplasia due to 21-hydroxylase deficiency. A1 - Forest,Maguelone G, PY - 2004/10/30/pubmed PY - 2005/3/24/medline PY - 2004/10/30/entrez SP - 469 EP - 85 JF - Human reproduction update JO - Hum Reprod Update VL - 10 IS - 6 N2 - Congenital adrenal hyperplasias (CAH) are inherited defects of cortisol biosynthesis. More than 90% of CAH are caused by 21-hydroxylase deficiency (21-OHD), found in 1:10 000 to 1:15 000 live births. Females with 'classical' 21-OHD, being exposed to excess androgens prenatally, are born with virilized external genitalia. Potentially lethal adrenal insufficiency is characteristic of two-thirds to three-quarters of patients with the classical salt wasting (SW) form of 21-OHD. Non-SW 21-OHD may be diagnosed on genital ambiguity in affected females, and/or later on the occurrence of androgen excess in both sexes. Non-classical 21-OHD, detected in > or =1:100 of certain populations, may present as precocious pubarche in children or polycystic ovarian syndrome in young women. 21-OHD is caused by mutations in the CYP21 gene encoding the steroid 21-hydroxylase enzyme. More than 90% of these mutations result from intergenic recombination between CYP21 and the closely linked CYP21P pseudogene. The degree to which each mutation compromises enzymatic activity is strongly correlated with the clinical severity of the disorder. This close association between genotype and phenotype makes it possible to predict clinical outcome in affected subjects. The risk of SW and prenatal virilization can be estimated, and overtreatment can be avoided in mildly affected cases. Glucocorticoid and mineralocorticoid replacement therapies are the mainstays of treatment, but additional therapies are being developed. A first trimester prenatal diagnosis should be proposed in families in whom molecular studies have been performed previously. The state of heterozygotism can be predicted by hormonal testing and confirmed by molecular studies. Prenatal diagnosis by direct mutation detection in previously genotyped families permits prenatal treatment of affected females in order to avoid or minimize genital virilization. Neonatal screening by hormonal methods identifies affected children before SW crises develop, reducing mortality in this disorder. SN - 1355-4786 UR - https://www.unboundmedicine.com/medline/citation/15514016/Recent_advances_in_the_diagnosis_and_management_of_congenital_adrenal_hyperplasia_due_to_21_hydroxylase_deficiency_ L2 - https://academic.oup.com/humupd/article-lookup/doi/10.1093/humupd/dmh047 DB - PRIME DP - Unbound Medicine ER -