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The Diagnosis of Congenital Adrenal Hyperplasia in the Newborn by Gas Chromatography/Mass Spectrometry Analysis of Random Urine Specimens

Quest Diagnostics’ Nichols Institute (M.P.C., T.L., R.E.R., D.A.F.), San Juan Capistrano, California 92690; Department of Pediatrics, University of California, San Diego (M.E.G., K.L.J.), La Jolla, California 92123; Department of Clinical Biochemistry, King’s College and School of Medicine (N.F.T.), London SE5 8RX, United Kingdom; Department of Laboratory Diagnostics, Children’s Memorial Health Institute (E.M.M.), Warsaw, Poland; and Children’s Hospital Oakland Research Institute (C.H.L.S.), Oakland, California 94609

Address all correspondence and requests for reprints to: Cedric H. L. Shackleton, Ph.D., Children’s Hospital Oakland Research Institute, 5700 Martin Luther King, Jr. Way, Oakland, California 94609. E-mail: . cshackleton{at}chori.org

Abstract

Definitive neonatal diagnosis of congenital adrenal hyperplasia (CAH) is frequently complicated by normal 17-hydroxyprogesterone levels in 21-hydroxylase-deficient patients, residual maternal steroids, and other interfering substances in neonatal blood. In an effort to improve the diagnosis, we developed a gas chromatography/mass spectrometry method for simultaneous measurement of 15 urinary steroid metabolites as early as the first day of life. Furthermore, we developed 11 precursor/product ratios that diagnose and clearly differentiate the four enzymatic deficiencies that cause CAH. Random urine samples from 31 neonatal 21-hydroxylase-deficient patients and 59 age-matched normal newborns were used in the development. Additionally, samples from two 11ß-hydroxylase-deficient patients and one patient each for 17 -hydroxylase and 3ß-hydroxysteroid dehydrogenase deficiencies were used. The throughput for one bench-top gas chromatography/mass spectrometry instrument is 20 samples per day. Thus, this method affords an accurate, rapid, noninvasive means for the differential diagnosis of CAH in the newborn period without the need for invasive testing and ACTH stimulation.

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