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Neonatal screening for congenital adrenal hyperplasia

Nature Reviews Endocrinology volume 5, pages 490–498 (2009)Cite this article

Abstract

Congenital adrenal hyperplasia (CAH) caused by steroid 21-hydroxylase deficiency occurs in 1:16,000–1:20,000 births. If not promptly diagnosed and treated, CAH can cause death in early infancy from shock, hyponatremia and hyperkalemia. Affected girls usually have ambiguous genitalia but boys appear normal; therefore, newborn babies are commonly screened for CAH in the US and many other countries. By identifying babies with severe, salt-wasting CAH before they develop adrenal crises, screening reduces morbidity and mortality, particularly among affected boys. Diagnosis is based on elevated levels of 17-hydroxyprogesterone, the preferred substrate for steroid 21-hydroxylase. Initial testing usually involves dissociation-enhanced lanthanide fluorescence immunoassay that has a low positive predictive value (about 1%), which leads to many follow-up evaluations that have negative results. The positive predictive value might be improved by second-tier screening using DNA-based methods or liquid chromatography followed by tandem mass spectrometry, but these methods are not widely adopted. Cost estimates for such screening range from US$20,000 to $300,000 per life-year saved. In babies with markedly abnormal screen results, levels of serum electrolytes and 17-hydroxyprogesterone should be immediately determined, but the most reliable way to diagnose CAH is measurement of levels of steroid precursors after stimulation with cosyntropin.

Key Points

  • Neonatal screening for congenital adrenal hyperplasia (CAH) caused by steroid 21-hydroxylase deficiency has been widely adopted in the US and many other countries

  • Neonatal screening for CAH reduces morbidity and mortality, particularly among boys, by identifying infants with the severe, salt-wasting form of CAH before they develop adrenal crises

  • Initial testing usually consists of an immunoassay for 17-hydroxyprogesterone levels; this assay has a low positive predictive value (approximately 1%), which results in many follow-up evaluations that have negative results

  • The positive predictive value might be improved by second-tier screening using DNA-based methods or liquid chromatography followed by tandem mass spectrometry, but these methods are not widely adopted yet

  • In infants with markedly abnormal test results, clinicians should immediately determine serum electrolyte and 17-hydroxyprogesterone levels and start treatment with hydrocortisone and fludrocortisone pending the results of hormonal tests

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Figure 1: Pathways of steroid biosynthesis in the adrenal cortex.
Figure 2: Algorithm for screening newborn babies for CAH.
Figure 3: Nomogram for comparing 17-OHP levels before and 60 min after an intravenous bolus of cosyntropin in individuals with or without 21-hydroxylase deficiency.46

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Acknowledgements

Charles P. Vega, University of California, Irvine, CA, is the author of and is solely responsible for the content of the learning objectives, questions and answers of the MedscapeCME-accredited continuing medical education activity associated with this article.

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    Perrin C. White

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White, P. Neonatal screening for congenital adrenal hyperplasia. Nat Rev Endocrinol 5, 490–498 (2009). https://doi.org/10.1038/nrendo.2009.148

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