TY - JOUR
T1 - Non-classic congenital adrenal hyperplasia due to 21-hydroxylase deficiency revisited
T2 - An update with a special focus on adolescent and adult women
AU - Carmina, Enrico
AU - Dewailly, Didier
AU - Escobar-Morreale, Héctor F.
AU - Kelestimur, Fahrettin
AU - Moran, Carlos
AU - Oberfield, Sharon
AU - Witchel, Selma F.
AU - Azziz, Ricardo
N1 - Publisher Copyright:
© The Author 2017.
PY - 2017/9/1
Y1 - 2017/9/1
N2 - BACKGROUND: Non-classic congenital hyperplasia (NCAH) due to 21-hydroxylase deficiency is a common autosomal recessive disorder characterized by androgen excess. OBJECTIVE AND RATIONALE: We conducted a systematic review and critical assessment of the available evidence pertaining to the epidemiology, pathophysiology, diagnosis and management of NCAH. A meta-analysis of epidemiological data was also performed. SEARCH METHODS: Peer-reviewed studies evaluating NCAH published up to October 2016 were reviewed. Multiple databases were searched including MEDLINE, EMBASE, Cochrane, ERIC, EBSCO, dissertation abstracts, and current contents. OUTCOMES: The worldwide prevalence of NCAH amongst women presenting with signs and symptoms of androgen excess is 4.2% (95% confidence interval: 3.2-5.4%). The clinical consequences of NCAH expand from infancy, i.e. accelerated growth, to adolescence and adulthood, i.e. premature pubarche, cutaneous symptoms and oligo-ovulation in a polycystic ovary syndrome (PCOS)-like clinical picture. The diagnosis of NCAH relies on serum 17-hydroxyprogesterone (17-OHP) concentrations. A basal 17-OHP concentration ≥2 ng/ml (6 nmol/l) should be used for screening if more appropriate in-house cut-offvalues are not available. Definitive diagnosis requires a 17-OHP concentration ≥10 ng/ml (30 nmol/l), either basally or after cosyntropin-stimulation. Molecular genetic analysis of the CYP21A2 gene, which is responsible for 21-hydroxylase activity, may be used for confirmation purposes and should be offered to all patients with NCAH along with genetic counseling because these patients frequently carry alleles that may result in classic CAH, the more severe form of the disease, in their progeny. Treatment must be individualized. Glucocorticoid replacement therapy may benefit pediatric patients with accelerated growth or advanced bone age or adult women seeking fertility, whereas adequate control of menstrual irregularity, hirsutism and other cutaneous symptoms is best served by the use of oral contraceptive pills and/or anti-androgens. Some women may need ovulation induction or assisted reproductive technology to achieve pregnancy. Patients with NCAH have a higher risk of miscarriage and may benefit from glucocorticoid treatment during pregnancy. WIDER IMPLICATIONS: Evidence-based diagnostic and treatment strategies are essential for the proper management of women with NCAH, especially considering that these patients may need different therapeutic strategies at different stages during their follow-up and that appropriate genetic counseling may prevent the occurrence of CAH in their children.
AB - BACKGROUND: Non-classic congenital hyperplasia (NCAH) due to 21-hydroxylase deficiency is a common autosomal recessive disorder characterized by androgen excess. OBJECTIVE AND RATIONALE: We conducted a systematic review and critical assessment of the available evidence pertaining to the epidemiology, pathophysiology, diagnosis and management of NCAH. A meta-analysis of epidemiological data was also performed. SEARCH METHODS: Peer-reviewed studies evaluating NCAH published up to October 2016 were reviewed. Multiple databases were searched including MEDLINE, EMBASE, Cochrane, ERIC, EBSCO, dissertation abstracts, and current contents. OUTCOMES: The worldwide prevalence of NCAH amongst women presenting with signs and symptoms of androgen excess is 4.2% (95% confidence interval: 3.2-5.4%). The clinical consequences of NCAH expand from infancy, i.e. accelerated growth, to adolescence and adulthood, i.e. premature pubarche, cutaneous symptoms and oligo-ovulation in a polycystic ovary syndrome (PCOS)-like clinical picture. The diagnosis of NCAH relies on serum 17-hydroxyprogesterone (17-OHP) concentrations. A basal 17-OHP concentration ≥2 ng/ml (6 nmol/l) should be used for screening if more appropriate in-house cut-offvalues are not available. Definitive diagnosis requires a 17-OHP concentration ≥10 ng/ml (30 nmol/l), either basally or after cosyntropin-stimulation. Molecular genetic analysis of the CYP21A2 gene, which is responsible for 21-hydroxylase activity, may be used for confirmation purposes and should be offered to all patients with NCAH along with genetic counseling because these patients frequently carry alleles that may result in classic CAH, the more severe form of the disease, in their progeny. Treatment must be individualized. Glucocorticoid replacement therapy may benefit pediatric patients with accelerated growth or advanced bone age or adult women seeking fertility, whereas adequate control of menstrual irregularity, hirsutism and other cutaneous symptoms is best served by the use of oral contraceptive pills and/or anti-androgens. Some women may need ovulation induction or assisted reproductive technology to achieve pregnancy. Patients with NCAH have a higher risk of miscarriage and may benefit from glucocorticoid treatment during pregnancy. WIDER IMPLICATIONS: Evidence-based diagnostic and treatment strategies are essential for the proper management of women with NCAH, especially considering that these patients may need different therapeutic strategies at different stages during their follow-up and that appropriate genetic counseling may prevent the occurrence of CAH in their children.
KW - 17-hydroxyprogesterone
KW - 21-hydroxylase deficiency
KW - Androgen excess
KW - Hirsutism
KW - Hyperandrogenism
KW - Miscarriage
KW - Non-classic congenital adrenal hyperplasia
KW - Polycystic ovary syndrome
KW - Pregnancy
KW - Prematurepubarche
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U2 - 10.1093/humupd/dmx014
DO - 10.1093/humupd/dmx014
M3 - Article
C2 - 28582566
AN - SCOPUS:85029418814
SN - 1355-4786
VL - 23
SP - 580
EP - 599
JO - Human Reproduction Update
JF - Human Reproduction Update
IS - 5
M1 - dmx014
ER -