This Article Full Text Full Text (PDF) Submit a related Letter to the Editor Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Copyright Permission Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Wudy, S. A. Articles by Homoki, J. Search for Related Content PubMed PubMed Citation Articles by Wudy, S. A. Articles by Homoki, J.

Profiling Steroid Hormones in Amniotic Fluid of Midpregnancy by Routine Stable Isotope Dilution/Gas Chromatography-Mass Spectrometry: Reference Values and Concentrations in Fetuses at Risk for 21-Hydroxylase Deficiency¹

Steroid Laboratory, Department of Pediatrics (S.A.W., C.S., J.H.), and Department of Medical Genetics (M.D.), University of Ulm, D-89070 Ulm/Donau; and the Department of Pediatric Endocrinology, University of Erlangen (H.G.D.), D-91054 Erlangen, Germany

Address all correspondence and requests for reprints to: PD Dr. Stefan A. Wudy, Steroid Laboratory, Department of Pediatrics, University of Ulm, D-89070 Ulm, Germany. E-mail: stefan.wudy{at}medizin

Using routine stable isotope dilution/gas chromatography-mass spectrometry, 17-hydroxyprogesterone, androstenedione, testosterone, dehydroepiandrosterone, androstanediol, and 5-dihydrotestosterone have been profiled in amniotic fluid of midgestation in 77 normal fetuses and 38 untreated or dexamethasone-treated fetuses at risk for 21-hydroxylase deficiency. Dexamethasone was suspended 5–7 days before amniocentesis. In normal fetuses, amniotic fluid concentrations (median, range; nanograms per mL) of 17-hydroxyprogesterone did not reveal a sex difference (1.48, 0.21–4.96), whereas those of androstenedione were lower in females (0.53, 0.00–2.71) than in males (0.93, 0.29–1.98). Testosterone levels were higher in males (0.24, 0.00–0.50) than in females (0.00, 0.00–0.27). No sex difference was found for dehydroepiandrosterone (0.47, 0.19–1.77). Levels of androstanediol and 5-dihydrotestosterone were below the detection limit of our method in most cases. Regarding prenatal diagnosis of 21-hydroxylase deficiency, 17-hydroxyprogesterone and androstenedione presented the diagnostically most valuable steroids and were of equal diagnostic potential. They permitted successful diagnosis in 36 of 37 fetuses at risk: 12 were untreated and unaffected, 13 were treated and unaffected, 4 were untreated and affected (3 salt wasters and 1 simple virilizer), and 8 were treated and affected (5 salt wasters and 3 simple virilizers). In the latter group, one simple virilizer revealed normal steroid concentrations. Isotope dilution/gas chromatography-mass spectrometry, providing the highest specificity in steroid analysis, is proposed for routine use in clinical steroid analysis whenever maximal reliability is requested. Our study provides the first mass spectrometric reference data on amniotic fluid steroid concentrations and underscores the high accuracy of prenatal hormonal diagnosis of 21-hydroxylase deficiency.

This article has been cited by other articles:

				P.-Y. Wang, A. Protheroe, A. N. Clarkson, F. Imhoff, K. Koishi, and I. S. McLennan Mullerian inhibiting substance contributes to sex-linked biases in the brain and behavior PNAS, April 28, 2009; 106(17): 7203 - 7208. [Abstract] [Full Text] [PDF]

				M. M. Kushnir, T. Naessen, D. Kirilovas, A. Chaika, J. Nosenko, I. Mogilevkina, A. L. Rockwood, K. Carlstrom, and J. Bergquist Steroid Profiles in Ovarian Follicular Fluid from Regularly Menstruating Women and Women after Ovarian Stimulation Clin. Chem., March 1, 2009; 55(3): 519 - 526. [Abstract] [Full Text] [PDF]

				R. Anand-Ivell, R. Ivell, D. Driscoll, and J. Manson Insulin-like factor 3 levels in amniotic fluid of human male fetuses Hum. Reprod., May 1, 2008; 23(5): 1180 - 1186. [Abstract] [Full Text] [PDF]

				R. C. Knickmeyer and S. Baron-Cohen Topical Review: Fetal Testosterone and Sex Differences in Typical Social Development and in Autism J Child Neurol, October 1, 2006; 21(10): 825 - 845. [Abstract] [PDF]

				P. C. White and P. W. Speiser Congenital Adrenal Hyperplasia due to 21-Hydroxylase Deficiency Endocr. Rev., June 1, 2000; 21(3): 245 - 291. [Abstract] [Full Text]

				C G D Brook;, I. HUGHES;, and C. J H KELNAR Antenatal treatment of a mother bearing a fetus with congenital adrenal hyperplasia Arch. Dis. Child. Fetal Neonatal Ed., May 1, 2000; 82(3): 176F - 181. [Full Text]