Diagnosis
3
Newborn Screening
➤ Endocrine Society (ES) recommends that all newborn screening programs
incorporate screening for congenital adrenal hyperplasia due to
21-hydroxylase deficiency. (1|⊕⊕⊕
)
➤ ES recommends that first-tier screens use 17-hydroxyprogesterone assays
standardized to a common technology with norms stratified by gestational
age. (1|⊕⊕⊕
)
Technical remark: Clinicians should be aware that immunoassays are still in use and
remain a source of false-positive results. Specificity may be improved with organic
extraction to remove cross-reacting substances.
➤ ES recommends that screening laboratories employ a second-tier screen
by liquid chromatography–tandem mass spectrometry in preference to all
other methods (e.g., genotyping) to improve the positive predictive value of
congenital adrenal hyperplasia screening. (1|⊕⊕
)
Technical remark: Laboratories utilizing liquid chromatography–tandem mass
spectrometry should participate in an appropriate quality assurance program.
Additionally, clinicians should realize that immunoassays lead to more false-positive
results. Thus, if laboratory resources do not include liquid chromatography–tandem
mass spectrometry, a cosyntropin stimulation test should be performed to confirm
diagnosis prior to initiation of corticosteroid treatment.
Diagnosis of Congenital Adrenal Hyperplasia
➤ In infants with positive newborn screens for congenital adrenal
hyperplasia, ES recommends referral to pediatric endocrinologists (if
regionally available) and evaluation by cosyntropin stimulation testing as
needed. (1|⊕⊕⊕
)
➤ In symptomatic individuals past infancy, ES recommends screening with
an early-morning (before 8 AM) baseline serum 17-hydroxyprogesterone
measurement by liquid chromatography–tandem mass spectrometry.
(1|⊕⊕⊕
)
➤ In individuals with borderline 17-hydroxyprogesterone levels, ES
recommends obtaining a complete adrenocortical profile after a
cosyntropin stimulation test to differentiate 21-hydroxylase deficiency
from other enzyme defects. (1|⊕⊕⊕
)
➤ In individuals with congenital adrenal hyperplasia, ES suggests genotyping
only when results of the adrenocortical profile after a cosyntropin
stimulation test are equivocal, or cosyntropin stimulation cannot be
accurately performed (i.e., patient receiving glucocorticoid), or for
purposes of genetic counseling. (2|⊕⊕⊕
)
Technical remark: Genotyping at least one parent aids in the interpretation of genetic
test results because of the complexity of the CYP21A2 locus.
