Newborn screening for congenital adrenal hyperplasia: additional steroid profile using liquid chromatography-tandem mass spectrometry.
J Clin Endocrinol Metab
; 92(7): 2581-9, 2007 Jul.
Article
in En
| MEDLINE
| ID: mdl-17456574
ABSTRACT
BACKGROUND:
Neonatal screening programs for congenital adrenal hyperplasia (21-CAH) using an immunoassay for 17alpha-hydroxyprogesterone (17-OHP) generate a high rate of positive results attributable to physiological reasons and to cross-reactions with steroids other than 17alpha-OHP, especially in preterm neonates and in critically ill newborns.METHODS:
To increase the specificity of the screening process, we applied a liquid chromatography-tandem mass spectrometry method quantifying 17alpha-OHP, 11-deoxycortisol, 21-deoxycortisol, cortisol, and androstenedione. The steroids were eluted in aqueous solution containing d8-17alpha-OHP and d2-cortisol and quantified in multiple reaction mode.RESULTS:
Detection limit was below 1 nmol/liter, and recovery ranged from 64% (androstenedione) to 83% (cortisol). Linearity was proven within a range of 5-100 nmol/liter (cortisol, 12.5-200 nmol/liter), and total run time was 6 min. Retrospective analysis of 6151 blood samples and 50 blood samples from newborns with clinically confirmed 21-CAH, as well as prospective analysis of 1609 samples of a total of 242,500 testing positive in our routine 17-OHP immunoassay, allowed clear distinction of affected and nonaffected newborns. High levels of 21-deoxycortisol were only found in children with 21-hydroxylase deficiency. Calculating the ratio of 17alpha-OHP to 21-deoxycortisol divided by cortisol further increased the sensitivity of the method.CONCLUSION:
Our liquid chromatography-tandem mass spectrometry procedure as a second-tier test can be used to reduce false-positive results of standard 21-CAH screening. The short total run time of 6 min allows for immediate reanalysis of all immunoassay results above the cutoff.
Search on Google
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Neonatal Screening
/
Adrenal Hyperplasia, Congenital
/
17-alpha-Hydroxyprogesterone
/
Cortodoxone
Type of study:
Diagnostic_studies
/
Observational_studies
/
Screening_studies
Limits:
Female
/
Humans
/
Male
/
Newborn
Language:
En
Journal:
J Clin Endocrinol Metab
Year:
2007
Document type:
Article
Affiliation country:
Germany