Reduced Activity of 11β-Hydroxylase Accounts for Elevated 17α-Hydroxyprogesterone in Preterms

doi:10.1016/j.jpeds.2014.04.011

The Journal of Pediatrics

Volume 165, Issue 2, August 2014, Pages 280-284

https://doi.org/10.1016/j.jpeds.2014.04.011 Get rights and content

Objective

To characterize the urinary steroid metabolome of neonates and infants born either at term or preterm.

Study design

We retrospectively analyzed urinary steroid hormone metabolites determined by gas chromatography–mass spectrometry of 78 neonates and infants born at term and 83 neonates and infants born preterm (median 34 weeks of gestational age). The subjects' 11β-hydroxylase and 21-hydroxylase activities were assessed on the basis of urinary metabolite substrate–to–product ratios.

Results

Preterm neonates and infants had elevated urinary concentrations of 17α-hydroxyprogesterone (17OHP) metabolites (P < .001) but lower urinary concentrations of the 21-deoxycortisol metabolite pregnanetriolone (PTO) (P < .01). One reason was lower 11β-hydroxylase activity in preterms. We could demonstrate a correlation between low 11β-hydroxylase activity and high urinary concentrations of 17OHP metabolites (r = 0.51, P < .001) but low urinary concentrations of the 21-deoxycortisol metabolite PTO (r = −0.24, P = .03) in preterms.

Conclusions

Low 11β-hydroxylase activity may explain increased 17OHP but decreased 21-deoxycortisol metabolite excretion in preterms. Our analysis clarifies, first, why preterms have higher 17OHP levels and thus higher rates of false-positive screening results for congenital adrenal hyperplasia than do term infants, and, second, why 21-deoxycortisol or its urinary metabolite PTO is more specific than 17OHP for the diagnosis of 21-hydroxylase deficiency.

Section snippets

Methods

Our retrospective study consisted of 78 term neonates and infants (median 24 postnatal days, range 3-161 days) and 83 preterm (median 34 weeks of gestational age, range 24-36 weeks) neonates and infants (median 24 postnatal day, range 5-142 days). All had a positive newborn screen for CAH with an elevated dried blood spot 17OHP value. The urinary gas chromatography–mass spectrometry (GC-MS) analysis was performed as a second tier test to definitively establish or exclude CAH.⁷ CAH was excluded

Results

Preterm neonates and infants had markedly elevated urinary concentrations of 17OHP metabolites, whereas the urinary excretion values of the glucocorticoid metabolite THE did not differ (Figure 2, A and B).

In contrast to the 17OHP metabolites, urinary concentrations of the 21-deoxycortisol metabolite PTO were significantly lower in preterm neonates and infants than in term infants (P < .01). In term neonates and infants, PTO was below the lowest limit of detection (<2.2 μg/L) in 40 of 78 samples

Discussion

Elevation of 17OHP in preterm infants is a well-known problem in NBS of CAH. In a report from France, the positive predictive value of a positive screening test was only 0.4% in preterm infants, whereas it was 30.1% in term infants.¹⁸

A physiologically reduced activity of the 11β-hydroxylase was reported previously in a study of 25 premature infants by Hingre et al.¹¹ They have demonstrated an elevated 11-deoxycortisol–to–cortisol ratio in preterm infants. Our results confirm this finding. We

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: The authors declare no conflicts of interest.

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Original ArticleReduced Activity of 11β-Hydroxylase Accounts for Elevated 17α-Hydroxyprogesterone in Preterms

Objective

Study design

Results

Conclusions

Section snippets

Methods

Results

Discussion

J Steroid Biochem

Steroids

Clin Chim Acta

J Steroid Biochem

J Steroid Biochem

J Steroid Biochem

Congenital adrenal hyperplasia due to 21-hydroxylase deficiency

Endocr Rev

Neonatal screening for congenital adrenal hyperplasia: 17-hydroxyprogesterone levels and CYP21 genotypes in preterm infants

Pediatrics

Comparison of one-tier and two-tier newborn screening metrics for congenital adrenal hyperplasia

Pediatrics

Original Article
Reduced Activity of 11β-Hydroxylase Accounts for Elevated 17α-Hydroxyprogesterone in Preterms