From the Guidelines
Testing for Congenital Adrenal Hyperplasia (CAH) should be done immediately in newborns with bilateral nonpalpable testes or ambiguous genitalia, as failure to diagnose CAH can result in serious harm, including shock, hyponatremia, and hyperkalemia. This is because a newborn with a male phallus and bilateral nonpalpable gonads is potentially a genetic female (46 XX) with congenital adrenal hyperplasia until proven otherwise 1. Additionally, testing is recommended when infants present with signs of precocious puberty or when children show symptoms of adrenal insufficiency, such as fatigue, weight loss, and low blood pressure, or if there's unexplained hirsutism in females.
Key Considerations
- Newborns with bilateral nonpalpable testes should be evaluated for disorder of sexual development and should not be circumcised until after the workup is complete, even if a completely normal phenotypic penis is documented on examination 1.
- A 46 XX individual with severe congenital adrenal hyperplasia can be mistaken for a boy with bilateral cryptorchidism, highlighting the importance of prompt evaluation and testing 1.
- Early detection and treatment of CAH are crucial for proper management of the condition and prevention of potential complications, including adrenal crisis and incorrect gender assignment 1.
Recommendations for Testing
- Testing for CAH should be considered in the following scenarios:
- Newborns with bilateral nonpalpable testes or ambiguous genitalia
- Infants with signs of precocious puberty
- Children with symptoms of adrenal insufficiency, such as fatigue, weight loss, and low blood pressure
- Females with unexplained hirsutism
- Individuals with a family history of CAH It's essential to note that there are classic and non-classic forms of CAH, with the classic form typically identified in infancy and the non-classic form potentially diagnosed later in childhood or adulthood 1.
From the Research
When to Test for Congenital Adrenal Hyperplasia (CAH)
- Newborn screening for CAH is recommended as it can identify the majority of classical cases, including salt-wasting and simple-virilizing forms, during the first days of life 2, 3, 4.
- Screening is particularly important for affected boys who may not exhibit obvious symptoms at birth, and for affected girls with mild genital ambiguity 2, 4.
- The initial screening test typically involves a dissociation-enhanced lanthanide fluorescence immunoassay, which measures the level of 17-hydroxyprogesterone, the preferred substrate for steroid 21-hydroxylase 4.
- A two-tier protocol, including an initial immunoassay or time-resolved fluoroimmunoassay followed by liquid chromatography tandem mass spectrometry, is recommended for confirmation of screen-positive babies 2.
- Molecular and genetic testing can be useful in prenatal diagnosis and genetic counseling for future pregnancies, but is not essential for establishing the diagnosis in all screen-positive babies 2, 3, 5, 6.
- Long-read sequencing-based approaches, such as comprehensive analysis of CAH (CACAH), have shown promise in accurately and reliably determining CAH genotypes, including the detection of pathogenic variants and the determination of cis-trans configuration 5, 6.