Abstract
Immunoassay-based 17-hydroxyprogesterone measurement, still the most widely used first-line test for suspected congenital
adrenal hyperplasia (CAH), carries a well-documented false-positive rate driven by cross-reactivity with structurally related
steroids, particularly in the preterm and low-birth-weight neonates who make up a disproportionate share of positive newborn
screening results. This perspective sets out why liquid chromatography-tandem mass spectrometry (LC-MS/MS) steroid profiling,
measuring 17-hydroxyprogesterone alongside several other steroids in the same biosynthetic pathway, offers a materially more
specific second-tier test, and addresses the practical barriers -- capital cost, specialist staffing, and the smaller sample volume
tolerance of the typical dried blood spot screening specimen -- that have kept many laboratories from adopting it despite broad
professional endorsement of the second-tier approach.
References
Speiser PW, Arlt W, Auchus RJ, et al. "Congenital adrenal hyperplasia due to steroid 21-hydroxylase deficiency: an Endocrine Society clinical practice guideline". J Clin Endocrinol Metab 103(2018): 4043-4088.
Held PK, Bird IM, Heather NL. "Newborn screening for congenital adrenal hyperplasia: review of factors affecting screening accuracy". Int J Neonatal Screen 6(2020): 67.
Janzen N, Peter M, Sander S, et al. "Newborn screening for congenital adrenal hyperplasia: additional steroid profile using liquid chromatography-tandem mass spectrometry". J Clin Endocrinol Metab 92(2007): 2581-2589.
Minutti CZ, Lacey JM, Magera MJ, et al. "Steroid profiling by tandem mass spectrometry improves the positive predictive value of newborn screening for congenital adrenal hyperplasia". J Clin Endocrinol Metab 89(2004): 3687-3693.
Schwarz E, Liu A, Randall H, et al. "Use of steroid profiling by UPLC-MS/MS as a second tier test in newborn screening for congenital adrenal hyperplasia". Clin Chim Acta 405(2009): 106-112.
Rossi C, Calton L, Hammond G, et al. "Serum steroid profiling for congenital adrenal hyperplasia using liquid chromatography-tandem mass spectrometry". Clin Chim Acta 411(2010): 222-228.
Turpeinen U, Hamalainen E. "Determination of cortisol in serum, saliva and urine". Best Pract Res Clin Endocrinol Metab 27(2013): 795-801.
Kosicka K, Siemiatkowska A, Krzyscin M, et al. "Novel LC-MS/MS method for simultaneous quantification of six steroids in dried blood spots". J Pharm Biomed Anal 155(2018): 62-68.
Fingerhut R. "False positive rate in newborn screening for congenital adrenal hyperplasia (CAH)-ether extraction reveals two distinct reasons for elevated 17alpha-hydroxyprogesterone (17-OHP) values". Steroids 74(2009): 662-665.
Chan CL, McFann K, Taylor L, et al. "Congenital adrenal hyperplasia and the second newborn screen". J Pediatr 163(2013): 109-113.
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