Virilising 21-hydroxylase deficiency: timing of newborn screening and confirmatory tests can be crucial

Early diagnosis of congenital adrenal hyperplasia (CAH) can be lifesaving. With the advent of newborn screening programs employing blood 17-hydroxyprogesterone, fewer cases are missed. Because false positive results occur, especially in premature and low birth weight babies, infants with borderline elevations, although requiring follow-up, are often considered normal. We describe a newborn female that, despite severe virilization, only had a borderline elevation in 17-hydroxyprogesterone (17OHP) on newborn screening, as well as on initial confirmatory testing in our clinical laboratory. Our confirmatory method, which employs high performance liquid chromatography (HPLC) separation, because of its high specificity, yields steroid values from both normal children and those with CAH that are lower than found with older, less specific methods. Given the heterogeneity of phenotypes of CAH, less severe forms, especially in males, could result in marginally abnormal laboratory results early in life, with possible adverse effects later. Although in retrospect the diagnosis of the described patient was clear and not a novel entity, we consider it an important example for several reasons. It emphasizes the broad range of 17OHP levels in CAH, the lack of correlation of these levels with clinical phenotype and the importance of the timing of both screening and confirmatory tests. Due to the complexity of interpreting these tests, any screening program for CAH should be controlled by an experienced pediatric endocrinologist.