Introduction
Introduction
Congenital adrenal hyperplasia (CAH) is a genetic disorder caused by an enzyme deficiency that leads to impaired cortisol synthesis and an excess of androgen production. The most common form of CAH is due to 21-hydroxylase deficiency, which accounts for over 95% of cases. Newborn screening for CAH due to 21-hydroxylase deficiency is recommended by the Endocrine Society as part of routine newborn screening programs.
First-tier screening uses 17-hydroxyprogesterone (17-OHP) assays, which should be standardized to a common technology with norms stratified by gestational age. Clinicians should be aware that immunoassays are still in use and may result in false-positive results. Specificity may be improved with organic extraction to remove cross-reacting substances.
If the first-tier screen is positive, a second-tier screen by liquid chromatography-tandem mass spectrometry (LC-MS/MS) is recommended to improve the positive predictive value of screening. Laboratories utilizing LC-MS/MS should participate in an appropriate quality assurance program. Clinicians should realize that immunoassays lead to more false-positive results. Thus, if laboratory resources do not include LC-MS/MS, a cosyntropin stimulation test should be performed to confirm diagnosis prior to initiation of corticosteroid treatment.
In summary, CAH due to 21-hydroxylase deficiency is a genetic disorder that can be detected by newborn screening programs. First-tier screening should use 17-OHP assays with norms stratified by gestational age, and second-tier screening should use LC-MS/MS to improve the positive predictive value of screening. Clinicians should be aware of the limitations of immunoassays and consider confirmation with a cosyntropin stimulation test prior to initiating corticosteroid treatment.
