{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,10]],"date-time":"2026-03-10T19:14:04Z","timestamp":1773170044080,"version":"3.50.1"},"reference-count":61,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2026,3,10]],"date-time":"2026-03-10T00:00:00Z","timestamp":1773100800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.springernature.com\/gp\/researchers\/text-and-data-mining"},{"start":{"date-parts":[[2026,3,10]],"date-time":"2026-03-10T00:00:00Z","timestamp":1773100800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.springernature.com\/gp\/researchers\/text-and-data-mining"}],"funder":[{"DOI":"10.13039\/501100003478","name":"Ministry of Health, Labour and Welfare","doi-asserted-by":"publisher","award":["20FC1020"],"award-info":[{"award-number":["20FC1020"]}],"id":[{"id":"10.13039\/501100003478","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100009619","name":"Japan Agency for Medical Research and Development","doi-asserted-by":"publisher","award":["23ek0109630h0001"],"award-info":[{"award-number":["23ek0109630h0001"]}],"id":[{"id":"10.13039\/100009619","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Endocrine"],"DOI":"10.1007\/s12020-026-04573-z","type":"journal-article","created":{"date-parts":[[2026,3,10]],"date-time":"2026-03-10T01:26:29Z","timestamp":1773105989000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["A Two-Step LC-MS\/MS method to differentiate 21OHD and PORD in Screen-Positive newborns"],"prefix":"10.1007","volume":"91","author":[{"given":"Hisae","family":"Nakatani","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kazuhiro","family":"Watanabe","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Atsumi","family":"Tsuji-Hosokawa","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Akito","family":"Sutani","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yoko","family":"Saito","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shizuka","family":"Kirino","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Haruki","family":"Yamano","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ryuta","family":"Orimoto","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maki","family":"Gau","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Analia","family":"Yogi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nobuyuki","family":"Ishige","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Toshihiro","family":"Tajima","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tomonobu","family":"Hasegawa","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kei","family":"Takasawa","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Masatoshi","family":"Takagi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kenichi","family":"Kashimada","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2026,3,10]]},"reference":[{"key":"4573_CR1","doi-asserted-by":"publisher","unstructured":"Mass Screening Committee, Japanese Society for Pediatric Endocrinology, Japanese Society for Mass Screening, et al. Guidelines for diagnosis and treatment of 21-hydroxylase deficiency (2014 revision). Clin Pediatr Endocrinol et al., 2015;24(3):77\u2013105. https:\/\/doi.org\/10.1297\/cpe.24.77","DOI":"10.1297\/cpe.24.77"},{"issue":"11","key":"4573_CR2","doi-asserted-by":"publisher","first-page":"4043","DOI":"10.1210\/jc.2018-01865","volume":"103","author":"PW Speiser","year":"2018","unstructured":"P.W. Speiser, W. Arlt, R.J. Auchus et al., Congenital adrenal hyperplasia due to steroid 21-Hydroxylase deficiency: an endocrine society clinical practice guideline. J. Clin. Endocrinol. Metab. 103(11), 4043\u20134088 (2018). https:\/\/doi.org\/10.1210\/jc.2018-01865","journal-title":"J. Clin. Endocrinol. Metab."},{"issue":"3","key":"4573_CR3","doi-asserted-by":"publisher","first-page":"1002","DOI":"10.1210\/jc.2014-3168","volume":"100","author":"NL Heather","year":"2015","unstructured":"N.L. Heather, S.N. Seneviratne, D. Webster et al., Newborn screening for congenital adrenal hyperplasia in new Zealand, 1994\u20132013. J. Clin. Endocrinol. Metab. 100(3), 1002\u20131008 (2015). https:\/\/doi.org\/10.1210\/jc.2014-3168","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"4573_CR4","doi-asserted-by":"publisher","first-page":"209","DOI":"10.1186\/s12887-015-0529-y","volume":"15","author":"A Tsuji","year":"2015","unstructured":"A. Tsuji, K. Konishi, S. Hasegawa et al., Newborn screening for congenital adrenal hyperplasia in Tokyo, Japan from 1989 to 2013: a retrospective population-based study. BMC Pediatr. 15, 209 (2015). https:\/\/doi.org\/10.1186\/s12887-015-0529-y","journal-title":"BMC Pediatr."},{"issue":"2","key":"4573_CR5","doi-asserted-by":"publisher","first-page":"113","DOI":"10.1001\/archpediatrics.2011.774","volume":"166","author":"B Coulm","year":"2012","unstructured":"B. Coulm, J. Coste, V. Tardy et al., Efficiency of neonatal screening for congenital adrenal hyperplasia due to 21-hydroxylase deficiency in children born in Mainland France between 1996 and 2003. Arch. Pediatr. Adolesc. Med. 166(2), 113\u2013120 (2012). https:\/\/doi.org\/10.1001\/archpediatrics.2011.774","journal-title":"Arch. Pediatr. Adolesc. Med."},{"issue":"5","key":"4573_CR6","doi-asserted-by":"publisher","first-page":"1003","DOI":"10.1210\/jcem-45-5-1003","volume":"45","author":"S Pang","year":"1977","unstructured":"S. Pang, J. Hotchkiss, A.L. Drash, L.S. Levine, M.I. New, Microfilter paper method for 17 alpha-hydroxyprogesterone radioimmunoassay: its application for rapid screening for congenital adrenal hyperplasia. J. Clin. Endocrinol. Metab. 45(5), 1003\u20131008 (1977). https:\/\/doi.org\/10.1210\/jcem-45-5-1003","journal-title":"J. Clin. Endocrinol. Metab."},{"issue":"2","key":"4573_CR7","doi-asserted-by":"publisher","first-page":"87","DOI":"10.1007\/BF03350496","volume":"5","author":"S Piazzi","year":"1982","unstructured":"S. Piazzi, M. Capelli, M. Paolini et al., Neonatal screening for 21-hydroxylase deficiency: a microfilter paper method for 17-alpha-hydroxyprogesterone assay. J. Endocrinol. Invest. 5(2), 87\u201390 (1982). https:\/\/doi.org\/10.1007\/BF03350496","journal-title":"J. Endocrinol. Invest."},{"key":"4573_CR8","doi-asserted-by":"publisher","unstructured":"A. Tsuji-Hosokawa, K. Kashimada, Thirty-Year lessons from the newborn screening for congenital adrenal hyperplasia (CAH) in Japan. Int. J. Neonatal Screen. 7(3) (2021). https:\/\/doi.org\/10.3390\/ijns7030036","DOI":"10.3390\/ijns7030036"},{"issue":"7","key":"4573_CR9","doi-asserted-by":"publisher","first-page":"3904","DOI":"10.1210\/jc.2004-2136","volume":"90","author":"HJ van der Kamp","year":"2005","unstructured":"van der H.J. Kamp, C.G.M. Oudshoorn, B.H. Elvers et al., Cutoff levels of 17-alpha-hydroxyprogesterone in neonatal screening for congenital adrenal hyperplasia should be based on gestational age rather than on birth weight. J. Clin. Endocrinol. Metab. 90(7), 3904\u20133907 (2005). https:\/\/doi.org\/10.1210\/jc.2004-2136","journal-title":"J. Clin. Endocrinol. Metab."},{"issue":"6","key":"4573_CR10","doi-asserted-by":"publisher","first-page":"2179","DOI":"10.1210\/jc.2005-1890","volume":"91","author":"V Tonetto-Fernandes","year":"2006","unstructured":"V. Tonetto-Fernandes, S.H.V. Lemos-Marini, H. Kuperman, L.M. Ribeiro-Neto, I.T.N. Verreschi, C.E. Kater, Serum 21-Deoxycortisol, 17-Hydroxyprogesterone, and 11-deoxycortisol in classic congenital adrenal hyperplasia: clinical and hormonal correlations and identification of patients with 11beta-hydroxylase deficiency among a large group with alleged 21-hydroxylase deficiency. J. Clin. Endocrinol. Metab. 91(6), 2179\u20132184 (2006). https:\/\/doi.org\/10.1210\/jc.2005-1890","journal-title":"J. Clin. Endocrinol. Metab."},{"issue":"3","key":"4573_CR11","doi-asserted-by":"publisher","first-page":"195","DOI":"10.1159\/000337974","volume":"77","author":"N Janzen","year":"2012","unstructured":"N. Janzen, F.G. Riepe, M. Peter et al., Neonatal screening: identification of children with 11\u03b2-hydroxylase deficiency by second-tier testing. Horm. Res. Paediatr. 77(3), 195\u2013199 (2012). https:\/\/doi.org\/10.1159\/000337974","journal-title":"Horm. Res. Paediatr."},{"issue":"10","key":"4573_CR12","doi-asserted-by":"publisher","first-page":"618","DOI":"10.1056\/NEJM198509053131007","volume":"313","author":"JF Cara","year":"1985","unstructured":"J.F. Cara, T. Moshang, A.M. Bongiovanni, B.S. Marx, Elevated 17-hydroxyprogesterone and testosterone in a newborn with 3-beta-hydroxysteroid dehydrogenase deficiency. N Engl. J. Med. 313(10), 618\u2013621 (1985). https:\/\/doi.org\/10.1056\/NEJM198509053131007","journal-title":"N Engl. J. Med."},{"issue":"5","key":"4573_CR13","doi-asserted-by":"publisher","first-page":"334","DOI":"10.1159\/000336004","volume":"77","author":"DD Jeandron","year":"2012","unstructured":"D.D. Jeandron, T. Sahakitrungruang, A novel homozygous Q334X mutation in the HSD3B2 gene causing classic 3\u03b2-hydroxysteroid dehydrogenase deficiency: an unexpected diagnosis after a positive newborn screen for 21-hydroxylase deficiency. Horm. Res. Paediatr. 77(5), 334\u2013338 (2012). https:\/\/doi.org\/10.1159\/000336004","journal-title":"Horm. Res. Paediatr."},{"issue":"6","key":"4573_CR14","doi-asserted-by":"publisher","first-page":"782","DOI":"10.1111\/cen.12394","volume":"80","author":"K Takasawa","year":"2014","unstructured":"K. Takasawa, M. Ono, A. Hijikata et al., Two novel HSD3B2 missense mutations with diverse residual enzymatic activities for \u22065-steroids. Clin. Endocrinol. (Oxf). 80(6), 782\u2013789 (2014). https:\/\/doi.org\/10.1111\/cen.12394","journal-title":"Clin. Endocrinol. (Oxf)"},{"issue":"3","key":"4573_CR15","doi-asserted-by":"publisher","first-page":"228","DOI":"10.1038\/ng1300","volume":"36","author":"CE Fl\u00fcck","year":"2004","unstructured":"C.E. Fl\u00fcck, T. Tajima, A.V. Pandey et al., Mutant P450 oxidoreductase causes disordered steroidogenesis with and without Antley-Bixler syndrome. Nat. Genet. 36(3), 228\u2013230 (2004). https:\/\/doi.org\/10.1038\/ng1300","journal-title":"Nat. Genet."},{"key":"4573_CR16","doi-asserted-by":"publisher","unstructured":"D. S\u00e1nchez-Garv\u00edn, S. Albaladejo, B. Ezquieta, R. Corripio, Disorder of sex development as a diagnostic clue in the first Spanish known newborn with P450 oxidoreductase deficiency. https:\/\/doi.org\/10.1136\/bcr-2013","DOI":"10.1136\/bcr-2013"},{"key":"4573_CR17","doi-asserted-by":"publisher","first-page":"432","DOI":"10.3389\/fendo.2019.00432","volume":"10","author":"D Pignatelli","year":"2019","unstructured":"D. Pignatelli, B.L. Carvalho, A. Palmeiro, A. Barros, S.G. Guerreiro, D. Macut, The complexities in genotyping of congenital adrenal hyperplasia: 21-Hydroxylase deficiency. Front. Endocrinol. (Lausanne). 10, 432 (2019). https:\/\/doi.org\/10.3389\/fendo.2019.00432","journal-title":"Front. Endocrinol. (Lausanne)"},{"issue":"5","key":"4573_CR18","doi-asserted-by":"publisher","first-page":"e2138","DOI":"10.1371\/journal.pone.0002138","volume":"3","author":"S Parajes","year":"2008","unstructured":"S. Parajes, C. Quinteiro, F. Dom\u00ednguez, L. Loidi, High frequency of copy number variations and sequence variants at CYP21A2 locus: implication for the genetic diagnosis of 21-hydroxylase deficiency. PLoS One. 3(5), e2138 (2008). https:\/\/doi.org\/10.1371\/journal.pone.0002138","journal-title":"PLoS One"},{"issue":"3","key":"4573_CR19","doi-asserted-by":"publisher","first-page":"750","DOI":"10.1210\/clinem\/dgad577","volume":"109","author":"E Adachi","year":"2024","unstructured":"E. Adachi, R. Nakagawa, A. Tsuji-Hosokawa et al., A MinION-based Long-Read sequencing application with One-Step PCR for the genetic diagnosis of 21-Hydroxylase deficiency. J. Clin. Endocrinol. Metab. 109(3), 750\u2013760 (2024). https:\/\/doi.org\/10.1210\/clinem\/dgad577","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"4573_CR20","doi-asserted-by":"publisher","unstructured":"Y. Gao, L. Lu, B. Yu et al., The prevalence of the chimeric TNXA\/TNXB gene and clinical symptoms of Ehlers-Danlos syndrome with 21-Hydroxylase deficiency. J. Clin. Endocrinol. Metab. 105(7) (2020). https:\/\/doi.org\/10.1210\/clinem\/dgaa199","DOI":"10.1210\/clinem\/dgaa199"},{"issue":"3","key":"4573_CR21","doi-asserted-by":"publisher","first-page":"255","DOI":"10.1159\/000524170","volume":"95","author":"P Cavarzere","year":"2022","unstructured":"P. Cavarzere, M. Camilot, L. Palma et al., Twenty years of neonatal screening for congenital adrenal hyperplasia in North-Eastern italy: role of liquid Chromatography-Tandem mass spectrometry as a Second-Tier test. Horm. Res. Paediatr. 95(3), 255\u2013263 (2022). https:\/\/doi.org\/10.1159\/000524170","journal-title":"Horm. Res. Paediatr."},{"issue":"5","key":"4573_CR22","doi-asserted-by":"publisher","first-page":"311","DOI":"10.1159\/000439380","volume":"84","author":"P Monostori","year":"2015","unstructured":"P. Monostori, P. Szab\u00f3, O. Marginean, C. Bereczki, E. Karg, Concurrent confirmation and differential diagnosis of congenital adrenal hyperplasia from dried blood spots: application of a Second-Tier LC-MS\/MS assay in a Cross-Border Cooperation for newborn screening. Horm. Res. Paediatr. 84(5), 311\u2013318 (2015). https:\/\/doi.org\/10.1159\/000439380","journal-title":"Horm. Res. Paediatr."},{"issue":"3","key":"4573_CR23","doi-asserted-by":"publisher","first-page":"621","DOI":"10.1373\/clinchem.2003.027193","volume":"50","author":"JM Lacey","year":"2004","unstructured":"J.M. Lacey, C.Z. Minutti, M.J. Magera et al., Improved specificity of newborn screening for congenital adrenal hyperplasia by second-tier steroid profiling using tandem mass spectrometry. Clin. Chem. 50(3), 621\u2013625 (2004). https:\/\/doi.org\/10.1373\/clinchem.2003.027193","journal-title":"Clin. Chem."},{"issue":"12","key":"4573_CR24","doi-asserted-by":"publisher","first-page":"3341","DOI":"10.1210\/clinem\/dgac521","volume":"107","author":"K Watanabe","year":"2022","unstructured":"K. Watanabe, A. Tsuji-Hosokawa, A. Hashimoto et al., The high relevance of 21-Deoxycortisol, (Androstenedione\u2009+\u200917\u03b1-Hydroxyprogesterone)\/Cortisol, and 11-Deoxycortisol\/17\u03b1-Hydroxyprogesterone for newborn screening of 21-Hydroxylase deficiency. J. Clin. Endocrinol. Metab. 107(12), 3341\u20133352 (2022). https:\/\/doi.org\/10.1210\/clinem\/dgac521","journal-title":"J. Clin. Endocrinol. Metab."},{"issue":"7","key":"4573_CR25","doi-asserted-by":"publisher","first-page":"2581","DOI":"10.1210\/jc.2006-2890","volume":"92","author":"N Janzen","year":"2007","unstructured":"N. Janzen, M. Peter, S. Sander et al., Newborn screening for congenital adrenal hyperplasia: additional steroid profile using liquid chromatography-tandem mass spectrometry. J. Clin. Endocrinol. Metab. 92(7), 2581\u20132589 (2007). https:\/\/doi.org\/10.1210\/jc.2006-2890","journal-title":"J. Clin. Endocrinol. Metab."},{"issue":"1","key":"4573_CR26","doi-asserted-by":"publisher","first-page":"121","DOI":"10.1515\/jpm-2013-0154","volume":"42","author":"JY Seo","year":"2014","unstructured":"J.Y. Seo, H.D. Park, J.W. Kim et al., Steroid profiling for congenital adrenal hyperplasia by tandem mass spectrometry as a second-tier test reduces follow-up burdens in a tertiary care hospital: A retrospective and prospective evaluation. Jpme. 42(1), 121\u2013127 (2014). https:\/\/doi.org\/10.1515\/jpm-2013-0154","journal-title":"Jpme"},{"issue":"3","key":"4573_CR27","doi-asserted-by":"publisher","first-page":"63","DOI":"10.3390\/ijns6030063","volume":"6","author":"F Lai","year":"2020","unstructured":"F. Lai, S. Srinivasan, V. Wiley, Evaluation of a Two-Tier screening pathway for congenital adrenal hyperplasia in the new South Wales newborn screening programme. Int. J. Neonatal Screen. 6(3), 63 (2020). https:\/\/doi.org\/10.3390\/ijns6030063","journal-title":"Int. J. Neonatal Screen."},{"issue":"4","key":"4573_CR28","doi-asserted-by":"publisher","first-page":"56","DOI":"10.3390\/ijns8040056","volume":"8","author":"MR de Hora","year":"2022","unstructured":"de M.R. Hora, N.L. Heather, D.R. Webster, B.B. Albert, P.L. Hofman, Evaluation of a new laboratory protocol for newborn screening for congenital adrenal hyperplasia in new Zealand. Int. J. Neonatal Screen. 8(4), 56 (2022). https:\/\/doi.org\/10.3390\/ijns8040056","journal-title":"Int. J. Neonatal Screen."},{"issue":"11","key":"4573_CR29","doi-asserted-by":"publisher","first-page":"e4487","DOI":"10.1210\/clinem\/dgab464","volume":"106","author":"K Stroek","year":"2021","unstructured":"K. Stroek, A. Ruiter, van der A. Linde et al., Second-tier testing for 21-Hydroxylase deficiency in the netherlands: A newborn screening pilot study. J. Clin. Endocrinol. Metab. 106(11), e4487\u2013e4496 (2021). https:\/\/doi.org\/10.1210\/clinem\/dgab464","journal-title":"J. Clin. Endocrinol. Metab."},{"issue":"1","key":"4573_CR30","doi-asserted-by":"publisher","first-page":"35","DOI":"10.1159\/000522230","volume":"95","author":"M Lind-Holst","year":"2022","unstructured":"M. Lind-Holst, M. B\u00e6kvad-Hansen, A. Berglund et al., Neonatal screening for congenital adrenal hyperplasia in denmark: 10 years of experience. Horm. Res. Paediatr. 95(1), 35\u201342 (2022). https:\/\/doi.org\/10.1159\/000522230","journal-title":"Horm. Res. Paediatr."},{"issue":"3","key":"4573_CR31","doi-asserted-by":"publisher","first-page":"33","DOI":"10.3390\/ijns5030033","volume":"5","author":"ER Bialk","year":"2019","unstructured":"E.R. Bialk, M.R. Lasarev, P.K. Held, Wisconsin\u2019s screening algorithm for the identification of newborns with congenital adrenal hyperplasia. Int. J. Neonatal Screen. 5(3), 33 (2019). https:\/\/doi.org\/10.3390\/ijns5030033","journal-title":"Int. J. Neonatal Screen."},{"issue":"23\u201324","key":"4573_CR32","doi-asserted-by":"publisher","first-page":"2076","DOI":"10.1016\/j.cca.2011.07.009","volume":"412","author":"K Dhillon","year":"2011","unstructured":"K. Dhillon, T. Ho, P. Rich et al., An automated method on analysis of blood steroids using liquid chromatography tandem mass spectrometry: application to population screening for congenital adrenal hyperplasia in newborns. Clin. Chim. Acta. 412(23\u201324), 2076\u20132084 (2011). https:\/\/doi.org\/10.1016\/j.cca.2011.07.009","journal-title":"Clin. Chim. Acta"},{"issue":"2","key":"4573_CR33","doi-asserted-by":"publisher","first-page":"230","DOI":"10.1203\/PDR.0b013e3181aa3777","volume":"66","author":"E Schwarz","year":"2009","unstructured":"E. Schwarz, A. Liu, H. Randall et al., Use of steroid profiling by UPLC-MS\/MS as a second tier test in newborn screening for congenital adrenal hyperplasia: the Utah experience. Pediatr. Res. 66(2), 230\u2013235 (2009). https:\/\/doi.org\/10.1203\/PDR.0b013e3181aa3777","journal-title":"Pediatr. Res."},{"issue":"4","key":"4573_CR34","doi-asserted-by":"publisher","first-page":"585","DOI":"10.1007\/s10545-007-0691-y","volume":"30","author":"D Matern","year":"2007","unstructured":"D. Matern, S. Tortorelli, D. Oglesbee, D. Gavrilov, P. Rinaldo, Reduction of the false-positive rate in newborn screening by implementation of MS\/MS-based second-tier tests: the Mayo clinic experience (2004\u20132007). J. Inherit. Metab. Dis. 30(4), 585\u2013592 (2007). https:\/\/doi.org\/10.1007\/s10545-007-0691-y","journal-title":"J. Inherit. Metab. Dis."},{"key":"4573_CR35","doi-asserted-by":"publisher","first-page":"109056","DOI":"10.1016\/j.steroids.2022.109056","volume":"185","author":"X Zhan","year":"2022","unstructured":"X. Zhan, L. Han, W. Qiu et al., Steroid profile in dried blood spots by liquid chromatography tandem mass spectrometry: application to newborn screening for congenital adrenal hyperplasia in China. Steroids. 185, 109056 (2022). https:\/\/doi.org\/10.1016\/j.steroids.2022.109056","journal-title":"Steroids"},{"issue":"1","key":"4573_CR36","doi-asserted-by":"publisher","first-page":"2024","DOI":"10.1297\/cpe.2024-0069","volume":"34","author":"T Tajima","year":"2025","unstructured":"T. Tajima, Newborn screening for congenital adrenal hyperplasia: utility of liquid chromatography with tandem mass spectrometry as a secondary test. Clin. Pediatr. Endocrinol. 34(1), 2024\u20130069 (2025). https:\/\/doi.org\/10.1297\/cpe.2024-0069","journal-title":"Clin. Pediatr. Endocrinol."},{"issue":"1","key":"4573_CR37","doi-asserted-by":"publisher","first-page":"bvad155","DOI":"10.1210\/jendso\/bvad155","volume":"8","author":"J Shim","year":"2023","unstructured":"J. Shim, C.H. Ahn, S.S. Park et al., Multiplexed serum steroid profiling reveals metabolic signatures of subtypes in congenital adrenal hyperplasia. J. Endocr. Soc. 8(1), bvad155 (2023). https:\/\/doi.org\/10.1210\/jendso\/bvad155","journal-title":"J. Endocr. Soc."},{"issue":"4","key":"4573_CR38","doi-asserted-by":"publisher","first-page":"741","DOI":"10.1373\/clinchem.2011.173286","volume":"58","author":"Y Koyama","year":"2012","unstructured":"Y. Koyama, K. Homma, M. Fukami et al., Two-step biochemical differential diagnosis of classic 21-hydroxylase deficiency and cytochrome P450 oxidoreductase deficiency in Japanese infants by GC-MS measurement of urinary pregnanetriolone\/ tetrahydroxycortisone ratio and 11\u03b2-hydroxyandrosterone. Clin. Chem. 58(4), 741\u2013747 (2012). https:\/\/doi.org\/10.1373\/clinchem.2011.173286","journal-title":"Clin. Chem."},{"issue":"2","key":"4573_CR39","doi-asserted-by":"publisher","first-page":"37","DOI":"10.1297\/cpe.25.37","volume":"25","author":"Y Koyama","year":"2016","unstructured":"Y. Koyama, K. Homma, M. Fukami et al., Classic and non-classic 21-hydroxylase deficiency can be discriminated from P450 oxidoreductase deficiency in Japanese infants by urinary steroid metabolites. Clin. Pediatr. Endocrinol. 25(2), 37\u201344 (2016). https:\/\/doi.org\/10.1297\/cpe.25.37","journal-title":"Clin. Pediatr. Endocrinol."},{"issue":"7","key":"4573_CR40","doi-asserted-by":"publisher","first-page":"3418","DOI":"10.1210\/jc.2010-0058","volume":"95","author":"J. Idkowiak","year":"2010","unstructured":"J. Idkowiak, E.M. Malunowicz, V. Dhir et al., Concomitant mutations in the P450 613 oxidoreductase and androgen receptor genes presenting with 46,XY disordered sex 614 development and androgenization at adrenarche. J. Clin. 615 Endocrinol. Metabolism. 95(7), 3418\u20133427 (2010) https:\/\/doi.org\/10.1210\/jc.2010-616-0058","journal-title":"J. Clin. 615 Endocrinol. Metabolism"},{"issue":"2","key":"4573_CR41","doi-asserted-by":"publisher","first-page":"276","DOI":"10.1203\/01.pdr.0000195825.31504.28","volume":"59","author":"M. Fukami","year":"2006","unstructured":"M. Fukami, T. Hasegawa, R. Horikawa et al., Cytochrome P450 oxidoreductase deficiency in three patients initially regarded as having 21-hydroxylase deficiency and\/or aromatase deficiency: Diagnostic value of urine steroid hormone analysis. 620 Pediatr. Res. 59(2), 276\u2013280 (2006) https:\/\/10.1203\/01.pdr.0000195825.31504.28","journal-title":"620 Pediatr. Res."},{"issue":"3","key":"4573_CR42","doi-asserted-by":"publisher","first-page":"624","DOI":"10.1210\/jc.2010-1607","volume":"96","author":"J. Idkowiak","year":"2011","unstructured":"J. Idkowiak, S. O\u2019Riordan, N. Reisch et al., Pubertal presentation in seven patients with congenital adrenal hyperplasia due to P450 oxidoreductase deficiency. J. Clin. Endocrinol. Metab. 96(3), 624 (2011) https:\/\/doi.org\/10.1210\/jc.2010-1607","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"4573_CR43","doi-asserted-by":"crossref","unstructured":"Zhang J, Woo KL, Hai Y, et al. Congenital adrenal hyperplasia due to P450 oxidoreductase deficiency. Front Endocrinol (Lausanne). 2022;13. doi:10.3389\/fendo.2022.1020880","DOI":"10.3389\/fendo.2022.1020880"},{"key":"4573_CR44","doi-asserted-by":"crossref","unstructured":"Huang N, Pandey A V, Agrawal V, et al. Diversity and Function of Mutations in P450 Oxidoreductase in Patients with Antley-Bixler Syndrome and Disordered Steroidogenesis. Vol 76.; 2005","DOI":"10.1086\/429417"},{"issue":"4","key":"4573_CR45","doi-asserted-by":"publisher","first-page":"939","DOI":"10.1093\/humrep\/deaa020","volume":"35","author":"G.E. Papadakis","year":"2021","unstructured":"G.E. Papadakis, A. Dumont, J. Bouligand et al., Non-classic cytochrome P450 oxidoreductase deficiency strongly linked with menstrual cycle disorders and 633 female infertility as primary manifestations. Hum. Reprod. 35(4), 939\u2013949 (2021) https:\/\/doi.org\/10.1093\/HUMREP\/DEAA020","journal-title":"Hum. Reprod."},{"issue":"12","key":"4573_CR46","doi-asserted-by":"publisher","first-page":"4992","DOI":"10.1210\/jc.2009-1460","volume":"94","author":"T. Sahakitrungruang","year":"2009","unstructured":"T. Sahakitrungruang, N. Huang, M.K. Tee et al., Clinical, genetic, and enzymatic characterization of P450 oxidoreductase deficiency in four patients. J. Clin. Endocrinol. Metab. 94(12), 4992\u20135000 (2009) https:\/\/doi.org\/10.1210\/jc.2009-1460","journal-title":"J. Clin. Endocrinol. Metab."},{"issue":"5","key":"4573_CR47","doi-asserted-by":"publisher","first-page":"500","DOI":"10.1590\/2359-3997000000213","volume":"60","author":"B.D.S.F. Bonamichi","year":"2016","unstructured":"B.D.S.F. Bonamichi, S.L.M. Santiago, D.R. Bertola et al., Long-term follow-up of a female with congenital adrenal hyperplasia due to P450-oxidoreductase deficiency. Arch. Endocrinol. Metab. 60(5), 500\u2013504 (2016) https:\/\/doi.org\/10.1590\/2359-3997000000213","journal-title":"Arch. Endocrinol. Metab."},{"issue":"12","key":"4573_CR48","doi-asserted-by":"publisher","first-page":"4789","DOI":"10.1210\/jc.2016-1928","volume":"101","author":"S. Parween","year":"2016","unstructured":"S. Parween, F. Roucher-Boulez, C.E. Fl\u00fcck et al., P450 oxidoreductase deficiency: Loss of activity caused by protein instability from a novel L374H mutation. J. Clin. Endocrinol. Metab. 101(12), 4789\u20134798 (2016) https:\/\/doi.org\/10.1210\/jc.2016-1928","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"4573_CR49","doi-asserted-by":"crossref","unstructured":"Bai Y, Li J, Wang X. Cytochrome P450 oxidoreductase deficiency caused by R457H mutation in POR gene in Chinese: Case report and literature review. J Ovarian Res.BioMed Central Ltd. 2017;10(1). doi:10.1186\/s13048-017-0312-9","DOI":"10.1186\/s13048-017-0312-9"},{"key":"4573_CR50","unstructured":"Zhang T, Li Z, Ren X, et al. Clinical and genetic analysis of cytochrome P450 oxidoreductase (POR) deficiency in a female and the analysis of a novel POR intron mutation causing alternative mRNA splicing Overall analysis of a female with POR deficiency. doi:10.1007\/s10815-020-01899-z\/Published"},{"issue":"4","key":"4573_CR51","doi-asserted-by":"publisher","first-page":"572","DOI":"10.1016\/j.bbrc.2011.08.001","volume":"412","author":"C.E. Fl\u00fcck","year":"2011","unstructured":"C.E. Fl\u00fcck, D. Mallet, G. Hofer et al., Deletion of P399_E401 in NADPH cytochrome P450 oxidoreductase results in partial mixed oxidase deficiency. Biochem. Biophys. Res. Commun. 412(4), 572\u2013577 (2011) https:\/\/doi.org\/10.1016\/j.bbrc.2011.08.001","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"4573_CR52","doi-asserted-by":"publisher","unstructured":"L. Fan, X. Ren, Y. Song, C. Su, J. Fu, C. Gong, Novel phenotypes and genotypes in Antley-Bixler syndrome caused by cytochrome P450 oxidoreductase deficiency: Based on the first cohort of Chinese children. Orphanet J. Rare Dis. 2019;14(1) https:\/\/doi.org\/10.1186\/s13023-019-1283-2","DOI":"10.1186\/s13023-019-1283-2"},{"issue":"1","key":"4573_CR53","doi-asserted-by":"publisher","first-page":"414","DOI":"10.1210\/jc.2004-0810","volume":"90","author":"M. Fukami","year":"2005","unstructured":"M. Fukami, R. Horikawa, T. Nagai et al., Cytochrome P450 oxidoreductase gene mutations and antley-bixler syndrome with abnormal genitalia and\/or impaired steroidogenesis: Molecular and clinical studies in 10 patients. J. Clin. Endocrinol. Metab. 90(1), 414\u2013426 (2005) https:\/\/doi.org\/10.1210\/jc.2004-0810","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"4573_CR54","doi-asserted-by":"publisher","unstructured":"P. Pan, L. Zheng, X. Chen, J. Huang, D. Yang, Y. Li, Successful live birth in a Chinese woman with P450 oxidoreductase deficiency through frozen-thawed embryo transfer: a case report with review of the literature. J. Ovarian Res. 2021;14(1) https:\/\/doi.org\/10.1186\/s13048-021-00778-0","DOI":"10.1186\/s13048-021-00778-0"},{"key":"4573_CR55","doi-asserted-by":"publisher","unstructured":"Greaves RF, Kumar M, Mawad N, et al. Best Practice for Identification of Classical 21-Hydroxylase Deficiency Should Include 21 Deoxycortisol Analysis with Appropriate Isomeric Steroid Separation. Int J Neonatal Screen.https:\/\/doi.org\/10.3390\/ijns9040058","DOI":"10.3390\/ijns9040058"},{"issue":"6","key":"4573_CR56","doi-asserted-by":"publisher","first-page":"416","DOI":"10.1159\/000501396","volume":"91","author":"W.L. Miller","year":"2019","unstructured":"W.L. Miller, Congenital Adrenal Hyperplasia: Time to Replace 17OHP with 21-Deoxycortisol. Horm. Res. Paediatr. 91(6), 416\u2013420 (2019) https:\/\/doi.org\/10.1159\/000501396","journal-title":"Horm. Res. Paediatr."},{"issue":"9","key":"4573_CR57","doi-asserted-by":"publisher","first-page":"e3714","DOI":"10.1210\/clinem\/dgab225","volume":"106","author":"M. Yildiz","year":"2021","unstructured":"M. Yildiz, E. Isik, Z.Y. Abali et al., Clinical and Hormonal Profiles Correlate With Molecular Characteristics in Patients With 11\u03b2-Hydroxylase Deficiency. J. Clin. Endocrinol. Metab. 106(9), e3714\u2013e3724 (2021) https:\/\/doi.org\/10.1210\/clinem\/dgab225","journal-title":"J. Clin. Endocrinol. Metab."},{"issue":"4","key":"4573_CR58","doi-asserted-by":"publisher","first-page":"e1718","DOI":"10.1210\/clinem\/dgaa022","volume":"105","author":"T. Guran","year":"2020","unstructured":"T. Guran, C. Kara, M. Yildiz et al., Revisiting Classical 3\u03b2-hydroxysteroid Dehydrogenase 2 Deficiency: Lessons from 31 Pediatric Cases. J. Clin. Endocrinol. Metab. 105(4), e1718\u2013e1728 (2020) https:\/\/doi.org\/10.1210\/clinem\/dgaa022","journal-title":"J. Clin. Endocrinol. Metab."},{"issue":"3","key":"4573_CR59","doi-asserted-by":"publisher","first-page":"317","DOI":"10.1210\/er.2010-0001","volume":"32","author":"H. Ishimoto","year":"2011","unstructured":"H. Ishimoto, R.B. Jaffe, Development and Function of the Human Fetal Adrenal Cortex: A Key Component in the Feto-Placental Unit. Endocr. Rev. 32(3), 317\u2013355 (2011) https:\/\/doi.org\/10.1210\/er.2010-0001","journal-title":"Endocr. Rev."},{"issue":"5","key":"4573_CR60","doi-asserted-by":"publisher","first-page":"2487","DOI":"10.1210\/endo-126-5-2487","volume":"126","author":"K.M. DOODY","year":"1990","unstructured":"K.M. DOODY, B.R. CARR, 3\u03b2-Hydroxysteroid Dehydrogenase\/Isomerase in the Fetal Zone and Neocortex of the Human Fetal Adrenal Gland*. Endocrinology. 126(5), 2487\u20132492 (1990) https:\/\/doi.org\/10.1210\/endo-126-5-2487","journal-title":"Endocrinology"},{"key":"4573_CR61","doi-asserted-by":"publisher","first-page":"32","DOI":"10.1016\/j.clinbiochem.2018.09.009","volume":"62","author":"J. van Helden","year":"2018","unstructured":"van J. Helden, R. Weiskirchen, Cross-method comparison of serum androstenedione measurement with respect to the validation of a new fully automated chemiluminescence immunoassay. Clin. Biochem. 62, 32\u201338 (2018) https:\/\/doi.org\/10.1016\/j.clinbiochem.2018.09.009","journal-title":"Clin. Biochem."}],"container-title":["Endocrine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s12020-026-04573-z.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s12020-026-04573-z","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s12020-026-04573-z.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,3,10]],"date-time":"2026-03-10T01:26:34Z","timestamp":1773105994000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s12020-026-04573-z"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,3,10]]},"references-count":61,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2026,12]]}},"alternative-id":["4573"],"URL":"https:\/\/doi.org\/10.1007\/s12020-026-04573-z","relation":{},"ISSN":["1559-0100"],"issn-type":[{"value":"1559-0100","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,3,10]]},"assertion":[{"value":"14 November 2025","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"28 January 2026","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"10 March 2026","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"The authors declare no competing interests.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflict of interests"}}],"article-number":"103"}}