From the Guidelines
Congenital adrenal hyperplasia (CAH) should be tested for in newborns with genital ambiguity as early as possible, preferentially within the first few weeks of life, to evaluate the chromosomal gonadal sex, hormonal environment, and anatomy of the external and internal genital organs. This is crucial for early gender assignment and to prevent potential complications associated with delayed diagnosis. According to 1, rapid detailed investigations must be performed in newborns with genital ambiguity to clarify the type of anomaly.
In addition to newborns with genital ambiguity, testing for CAH should also be considered in individuals with a family history of the condition, as well as those presenting with symptoms such as hirsutism, menstrual irregularities, or infertility. However, the most recent and highest quality study 2 does not provide direct evidence for the testing of CAH in these populations.
Key points to consider when testing for CAH include:
- Newborn screening is essential for early detection and prevention of complications
- Infants or children with signs of ambiguous genitalia, precocious puberty, or unexplained electrolyte imbalances should be tested for CAH
- Individuals with a family history of CAH should be considered for testing, particularly if they are considering having children
- Early detection and treatment of CAH can significantly improve morbidity, mortality, and quality of life outcomes.
It is essential to prioritize the testing of CAH in newborns with genital ambiguity, as early diagnosis and treatment can significantly impact the individual's quality of life and prevent potential complications. As stated in 1, female gender assignment is warranted in newborns with ambiguous genitalia secondary to congenital adrenal hyperplasia, and feminizing genitoplasty should be performed within the first 2 months of life to ensure consistency with the female sex of rearing.
From the Research
When to Test for Congenital Adrenal Hyperplasia (CAH)
- Testing for CAH can be done prenatally, as early as 10 weeks of gestation, to identify affected female fetuses and prevent virilization 3.
- Newborn screening for CAH is also recommended, as it can detect severe forms of the disease and reduce mortality, particularly among affected boys 4, 5.
- Screening can be done using a two-tier protocol, with initial immunoassay or time-resolved fluoroimmunoassay followed by liquid chromatography tandem mass spectrometry for confirmation of screen-positive babies 6.
- Antenatal diagnosis and treatment of CAH due to 21-hydroxylase deficiency can be considered, but it is still experimental and controversial, and should only be performed in experienced centers 7.
- Neonatal screening for 21-OHD CAH is effective in detecting severe forms and reducing mortality, and is instrumental in the correct sex assignment of female cases 7.
Timing of Testing
- Prenatal testing: as early as 10 weeks of gestation 3.
- Newborn screening: typically done in the first few days of life 6, 4, 5.
- Antenatal diagnosis and treatment: should be considered before the onset of genital organogenesis, typically before 10 weeks of gestation 7.
Methods of Testing
- Prenatal testing: can be done using amniocentesis or chorionic villus sampling 3.
- Newborn screening: can be done using a two-tier protocol, with initial immunoassay or time-resolved fluoroimmunoassay followed by liquid chromatography tandem mass spectrometry for confirmation of screen-positive babies 6.
- Antenatal diagnosis and treatment: can be done using molecular and genetic testing, but is still experimental and controversial 7.