Advances in congenital adrenal hyperplasia newborn screening: 11-ketotestosterone and 21-deoxycortisone as additional discriminatory biomarkers.

BACKGROUND: A major limitation of newborn screening (NBS) for congenital adrenal hyperplasia (CAH) is the lack of specificity of the fluoroimmunoassay (FIA) currently used for 17-hydroxyprogesterone (17OHP) determination. This issue is more pronounced in newborns, due to elevated levels of interfering compounds. Fluoroimmunoassay at our NBS centre in Ile-de-France has a false-positive rate of around 80% and a predictive positive value of 16% for first- and second-tier measurements from dried blood spots. Recently, tandem mass spectrometry (LC-MS/MS) has gained international recognition as a complementary tool to FIA testing. Currently, the most frequently used biomarkers are 17OHP and 21-deoxycortisol, used either alone or in combination with steroid ratios such as cortisol or 4-androstenedione. Concurrently, the class of 11-oxygenate-androgens-such as 11-ketotestosterone-and more recently 11-oxygenate pregnanes-such as 21-deoxycortisone-has attracted growing interest in the diagnosis of 21-hydroxylase deficiency. These derivatives result from the combined action of 11-beta hydroxysteroid dehydrogenase and 11-beta hydroxylase.

METHODS: We propose a revisited LC-MS/MS steroid profile, enriched with these classes of biomarkers, to be included in the CAH NBS algorithm. This combination could be used as a multi-steroid approach implemented using a machine learning model.

RESULTS: Our preliminary results suggest that these oxygenated androgen/pregnane steroids are significantly discriminative to streamline the NBS process for CAH. We have demonstrated this in 2 different NBS centres, in the greater Paris region and in Brittany, France.

CONCLUSION: This new algorithm could have an important impact on reducing the number of recall and family stress related to NBS.