Utility of a precursor-to-product ratio in the evaluation of presumptive positives in newborn screening of congenital adrenal hyperplasia

Abstract

TitleUtility of a precursor-to-product ratio in the evaluation of presumptive positives in newborn screening of congenital adrenal hyperplasia.ObjectiveScreening for Congenital Adrenal hyperplasia (CAH) caused by 21-α hydroxylase deficiency is challenging because factors such as prematurity and stress increase intermediate steroid metabolite levels in newborn infants. The objective of this study was to explore the use of the 17-OHP/11-deoxycortisol ratio as an adjunct measure in the follow-up evaluation of infants with presumptive positive newborn screens for CAH to distinguish between infants with no disorder and those with CAH.Study DesignThis was a retrospective cohort study of infants with presumptive positive newborn screens for CAH. The precursor-to-product ratio of 17-OHP/11-deoxycortisol was compared between infants with no disorder (n=47) and infants with CAH (n=5).ResultsThe CAH infants had higher 17-OHP/11-deoxycortisol ratios than infants with no disorder, 26 (18-58) and 1.05 (0.69-1.46), respectively, p<0.05. Among infants with no disorder, higher levels of serum 17-OHP did not reflect higher ratios, indicating sufficient enzyme activity.ConclusionsThe results suggest that a low 17-OHP/11-deoxycortisol ratio represents 21-α hydroxylase sufficiency among presumptive positives in newborn screening of CAH.

Evaluation of a Two-Tier Screening Pathway for Congenital Adrenal Hyperplasia in the New South Wales Newborn Screening Programme

“…There have been various studies investigating the feasibility of increasing the number of analytes in the steroid panel to increase specificity and sensitivity [ 44 , 45 , 46 , 47 , 48 ]. There are studies that show that the inclusion of 21-deoxycortisol and 11-deoxycortisol is more specific for detecting SWCAH by excluding β-hydroxylase deficiency [ 47 , 48 , 49 , 50 ]. Investigation of additional ratios (i.e., 17OHP + 21-deoxycortisol/cortisol) has been shown to be specific for 21 hydroxylase deficiency [ 49 ].…”

Implementing steroid profiling by liquid chromatography‐tandem mass spectrometry improves newborn screening for congenital adrenal hyperplasia in New Zealand

“…Delayed expression of 11β-hydroxylase, leading to increases in 11DF and reduced F in premature babies, has been described in a number of studies. 17,20 The subsequent elevations in the ratio 17OHP/11DF are therefore to be expected, however our study has shown that many neonates have much higher ratios than those encountered in premature babies in another study, 21 indicating that a higher ratio cut-off may be appropriate. Additionally, there was no difference in 17OHP/11DF values between our two BW groups with a negative screening result although the range of ratios in both groups is much wider than other steroid ratios.…”

Utility of a commercially available blood steroid profile in endocrine practice

“…[18] Although initial studies suggested ratios comprising 21-deoxycortisol which is not part of the steroid profile used in this study, recent studies have demonstrated the utility of ratios using 11-deoxycortisol as well. [1920] However, at present, the laboratory is not offering measurement 17-OHP or 11-deoxycortisol by LC MS/MS in a filter paper sample.…”