Newborn screening for congenital adrenal hyperplasia: Utility of liquid chromatography with tandem mass spectrometry as a secondary test

• Published in: Clinical Pediatric Endocrinology Vol. 34; no. 1; pp. 13 - 18
• Main Author: Tajima, Toshihiro
• Format: Journal Article
• Language: English
• Published: Japan The Japanese Society for Pediatric Endocrinology 2025
• Subjects: 11-deoxycortisol; congenital adrenal hyperplasia; false positive; liquid chromatography with tandem mass spectrometry; recall rate; Review; 11-deoxycortisol; recall rate; liquid chromatography with tandem mass spectrometry; false positive; congenital adrenal hyperplasia
• ISSN: 0918-5739; 1347-7358
• DOI: 10.1297/cpe.2024-0069

In Japan, newborn screening (NBS) for congenital adrenal hyperplasia (CAH) began in 1989. NBS is useful for early diagnosis and preventing gender misidentification, however, it has a higher false positive rate for CAH compared to other diseases detected by neonatal screening. Recently, it has become clear that using liquid chromatography with tandem mass spectrometry (LC-MS/MS) for second-tier testing reduces false positive rates and repeat blood sampling. LC-MS/MS commonly measures cortisol (F), androstenedione (A4), 11-deoxycortsiol (11DOF), 21-deoxycortisol (21DOF), and 17-hydroxyprogesterone (17OHP) levels. The ratios for (21DOF+17OHP)/F and (17OHP+A4)/F have been used to establish cut-off values for the second-tier test. In Japan, the recall rate is reduced using the 11DOF/17OHP ratio as well as the ratios for (21DOF+17OHP)/F and (17OHP+A4)/F for the second-tier test. Currently, second-tier testing using LC-MS/MS for CAH neonatal screening is unfeasible in all regions of Japan due to equipment costs, however, it will hopefully be available nationwide in the future.