Evidence map›Paper›PMID 41803588›Full record

ArticleEndocrine2026

A Two-Step LC-MS/MS method to differentiate 21OHD and PORD in Screen-Positive newborns.

Hisae Nakatani, Kazuhiro Watanabe, Atsumi Tsuji-Hosokawa, Akito Sutani, Yoko Saito, Shizuka Kirino, Haruki Yamano, Ryuta Orimoto, Maki Gau, Analia Yogi and 6 more

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Article in Endocrine, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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1 · What the graph read from it

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4 · The record

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5 · Who and what money

Authors and funding

16 authors.

Hisae NakataniDepartment of Pediatrics and Developmental Biology, Institute of Science Tokyo, 1-5-45 Yushima, Bunkyo-ku, 113-8510, Tokyo, Japan.
Kazuhiro WatanabeTokyo Health Service Association, Newborn Screening, 162-8402, Tokyo, Japan.
Atsumi Tsuji-HosokawaDepartment of Pediatrics and Developmental Biology, Institute of Science Tokyo, 1-5-45 Yushima, Bunkyo-ku, 113-8510, Tokyo, Japan.
Akito SutaniDepartment of Pediatrics and Developmental Biology, Institute of Science Tokyo, 1-5-45 Yushima, Bunkyo-ku, 113-8510, Tokyo, Japan.
Yoko SaitoDepartment of Pediatrics and Developmental Biology, Institute of Science Tokyo, 1-5-45 Yushima, Bunkyo-ku, 113-8510, Tokyo, Japan.
Shizuka KirinoDepartment of Pediatrics and Developmental Biology, Institute of Science Tokyo, 1-5-45 Yushima, Bunkyo-ku, 113-8510, Tokyo, Japan.
Haruki YamanoDepartment of Pediatrics and Developmental Biology, Institute of Science Tokyo, 1-5-45 Yushima, Bunkyo-ku, 113-8510, Tokyo, Japan.
Ryuta OrimotoDepartment of Pediatrics and Developmental Biology, Institute of Science Tokyo, 1-5-45 Yushima, Bunkyo-ku, 113-8510, Tokyo, Japan.
Maki GauDepartment of Life Science and Bioethics, Institute of Science Tokyo, 113-8510, Tokyo, Japan.
Analia YogiDepartment of Pediatrics and Developmental Biology, Institute of Science Tokyo, 1-5-45 Yushima, Bunkyo-ku, 113-8510, Tokyo, Japan.
Nobuyuki IshigeTokyo Health Service Association, Newborn Screening, 162-8402, Tokyo, Japan.
Toshihiro TajimaDepartment of Pediatrics, Jichi Medical University, 329-0498, Tochigi, Japan.
Tomonobu HasegawaDepartment of Pediatrics, Keio University School of Medicine, 160-8582, Tokyo, Japan.
Kei TakasawaDepartment of Pediatrics and Developmental Biology, Institute of Science Tokyo, 1-5-45 Yushima, Bunkyo-ku, 113-8510, Tokyo, Japan.
Masatoshi TakagiDepartment of Pediatrics and Developmental Biology, Institute of Science Tokyo, 1-5-45 Yushima, Bunkyo-ku, 113-8510, Tokyo, Japan.
Kenichi KashimadaDepartment of Pediatrics and Developmental Biology, Institute of Science Tokyo, 1-5-45 Yushima, Bunkyo-ku, 113-8510, Tokyo, Japan. kashimada-k@ncchd.go.jp.

Funding

Japan Agency for Medical Research and Development 23ek0109630h0001Ministry of Health, Labour and Welfare 20FC1020
6 · The paper itself

Abstract

backgroundThe multiplex steroid assay of liquid chromatography-tandem mass spectrometry (LC-MS/MS) has the potential to diagnose 21-hydroxylase deficiency (21OHD) directly from screening results.

aimTo establish an endocrinological diagnostic algorithm for 21OHD from screening positive cases based on LC-MS/MS screening.

methodsFor determining the cut-off criteria of 21-deoxycortisol (21DOF), the Tokyo screening cohort (21OHD, n = 26; false positives(FPs), n = 37) was examined. For identifying the biomarker to differentiate 21OHD from P450 oxidoreductase (POR) deficiency (PORD), another condition to cause 21DOF elevation in addition to 17α-OHP, we employed two cohorts from different origins, namely, 21OHD patients from the Tokyo screening cohort and the endocrinological data of previously reported PORD cases (n = 42 of 17 reports).

resultsThe 21DOF levels between 21OHD patients and FPs yielded 0.999 AUC. The combination of 17α-OHP > 15.1 nmol/L (5.0 ng/mL) and 21DOF > 2.88 nmol/L (1.0 ng/mL) yielded 1.000 and 0.949 of the positive and negative predictive values, respectively. Using both data, 21OHD and PORD can be narrowed down from other conditions in which 17α-OHP is elevated. To estimate 17,20-lyase activity, which is compromised only in PORD, we examined the androstenedione/cortisol (4AD/F) molar ratio, revealing a significant, non-overlapping difference (AUC, 1.000). Postnatal and gestational age dependency of the 4AD/F ratio was not apparent.

conclusionWe propose a two-step method to endocrinologically diagnose 21OHD in screening positive newborns. After, narrowing down to 21OHD and PORD using a cut-off of 21DOF > 2.88 nmol/L (1.0 ng/mL), a 4AD/F ratio > 0.06 would be indicative of 21OHD.

Indexed as

Adrenal Hyperplasia, CongenitalLiquid Chromatography-Mass SpectrometryNADPH-Ferrihemoprotein ReductaseNeonatal ScreeningTandem Mass Spectrometry17-alpha-HydroxyprogesteroneBiomarkersChromatography, LiquidCortodoxoneCytochrome P-450 Enzyme SystemDiagnosis, DifferentialFemaleHumansInfant, NewbornMale17-alpha-Hydroxyprogesterone21-deoxycortisolBiomarkersCortodoxoneCytochrome P-450 Enzyme SystemNADPH-Ferrihemoprotein ReductasePOR protein, human17α-hydroxyprogesterone21-hydroxylase deficiency (21OHD)AndrostenedioneDiagnosisP450 oxidoreductase deficiency (PORD)

Identifiers

PMID41803588

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