{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,2,21]],"date-time":"2025-02-21T08:21:32Z","timestamp":1740126092260,"version":"3.37.3"},"reference-count":40,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2021,7,8]],"date-time":"2021-07-08T00:00:00Z","timestamp":1625702400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100001807","name":"Funda\u00e7\u00e3o de Amparo \u00e0 Pesquisa do Estado de S\u00e3o Paulo","doi-asserted-by":"publisher","award":["#2014\/10325\u20107"],"award-info":[{"award-number":["#2014\/10325\u20107"]}],"id":[{"id":"10.13039\/501100001807","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Clinical Endocrinology"],"published-print":{"date-parts":[[2021,10]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Introduction<\/jats:title><jats:p>Heterozygotes (HZs) for 21\u2010hydroxylase deficiency (21OHD) are highly prevalent, ranging from 1:60 to 1:11 for classic and nonclassic (NC) forms, respectively. Detection of HZ and asymptomatic NC by <jats:italic>CYP21A2<\/jats:italic> genotyping is valuable for genetic counselling, but costly, complex\u00a0and narrowly available. Adrenocorticotropic hormone (ACTH)\u2010stimulated serum 17\u2010hydroxyprogesterone (17P) and 21\u2010deoxycortisol (21DF) discriminate 21OHD phenotypes effectively, notably if measured simultaneously by liquid chromatography\u2010tandem mass spectrometry (LC\u2010MS\/MS).<\/jats:p><\/jats:sec><jats:sec><jats:title>Objective<\/jats:title><jats:p>This study was performed to reassess former LC\u2010MS\/MS\u2010defined post\u2010ACTH 21DF, 17P\u00a0and cortisol (F) cutoffs in family members at risk for 21OHD.<\/jats:p><\/jats:sec><jats:sec><jats:title>Design and Patients<\/jats:title><jats:p>Prospective study in which we screened 58 asymptomatic relatives from families with 21OHD patients and compared post\u2010ACTH steroid phenotypes with subsequent genotypes.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Post\u2010ACTH 21DF, 17P, F\u00a0and (21DF\u2009+\u200917P)\/F ratio segregate NC, HZ and wild\u2010type (WT) phenotypes (subsequently genotyped) with some overlap. New receiver operating characteristic curve\u2010defined cutoffs for post\u2010ACTH 21DF, 17P and (21DF\u2009+\u200917P)\/F ratio are 60\u2009ng\/dl, 310\u2009ng\/dl and 12 (unitless). Twenty\u2010six of 33 HZ and all 6 NC (82.1%) had post\u2010ACTH 21DF\u2009&gt;\u200960\u00a0and 17P\u2009&gt;\u2009310\u2009ng\/dl, whereas 17\/19 WT (89.5%) had values below cutoffs. Post\u2010ACTH 21DF and 17P had a strong positive correlation (<jats:italic>r<\/jats:italic>\u2009=\u2009.9558; <jats:italic>p<\/jats:italic>\u2009&lt;\u2009.001). A (21DF\u2009+\u200917P)\/F ratio\u2009&gt;\u200912 correctly identified 36 of 39 HZ plus NC (92.3% sensitivity) with 84.2% specificity (16 of 19 WT). Given the high frequency of 21OHD HZ, the negative prediction of ratio values below 12 excludes heterozygosity in 99.8% and 99.1% for classic and NC mutations, respectively.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Reassessed ACTH\u2010stimulated 21DF and 17P cutoffs by LC\u2010MS\/MS (60 and 310\u2009ng\/dl, respectively) correctly recognised 82.5% HZ plus NC, but combined precursor\u2010to\u2010product ratio ([21DF\u2009+\u200917P]\/F) cutoff of 12 was superior, identifying 92.3% HZ plus NC. Since one WT subject is an outlier (potential HZ), these values would be somewhat better reinforcing their utility for screening asymptomatic relatives at risk for 21OHD.<\/jats:p><\/jats:sec>","DOI":"10.1111\/cen.14550","type":"journal-article","created":{"date-parts":[[2021,7,7]],"date-time":"2021-07-07T08:50:23Z","timestamp":1625647823000},"page":"677-685","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Reassessment of predictive values of ACTH\u2010stimulated serum 21\u2010deoxycortisol and 17\u2010hydroxyprogesterone to identify <i>CYP21A2<\/i> heterozygote carriers and nonclassic subjects"],"prefix":"10.1111","volume":"95","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3159-8434","authenticated-orcid":false,"given":"Fl\u00e1via A.","family":"Costa\u2010Barbosa","sequence":"first","affiliation":[{"name":"Adrenal and Hypertension Unit, Division of Endocrinology and Metabolism, Department of Medicine Steroids Laboratory, Federal University of S\u00e3o Paulo Medical School, EPM\/UNIFESP S\u00e3o Paulo Sao Paulo Brazil"},{"name":"Research and Development Division Fleury Medicina Diagn\u00f3stica S\u00e3o Paulo Sao Paulo Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Valdemir M.","family":"Carvalho","sequence":"additional","affiliation":[{"name":"Research and Development Division Fleury Medicina Diagn\u00f3stica S\u00e3o Paulo Sao Paulo Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kelly C.","family":"Oliveira","sequence":"additional","affiliation":[{"name":"Adrenal and Hypertension Unit, Division of Endocrinology and Metabolism, Department of Medicine Steroids Laboratory, Federal University of S\u00e3o Paulo Medical School, EPM\/UNIFESP S\u00e3o Paulo Sao Paulo Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jos\u00e9 Gilberto H.","family":"Vieira","sequence":"additional","affiliation":[{"name":"Adrenal and 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