{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2022,4,1]],"date-time":"2022-04-01T04:17:21Z","timestamp":1648786641902},"reference-count":34,"publisher":"Georg Thieme Verlag KG","funder":[{"name":"Ferring,\n                        Hexal\/Sandoz\/Novartis, NovoNordisk, Ipsen, Kyowa Kirin and\n                        Merck\/Serono."}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Exp Clin Endocrinol Diabetes"],"abstract":"<jats:title>Abstract<\/jats:title><jats:p>\n                    Background Mutations of CYP21A2 encoding 21-hydroxylase are the\n                    most frequent cause of congenital adrenal hyperplasia (CAH) and are associated\n                    either with elevated basal or ACTH-stimulated levels of 17-hydroxyprogesterone\n                    (17OHP) in blood.<\/jats:p><jats:p>\n                    Objective The study objective was to identify the most suitable of 12\n                    different test algorithms and appropriate cut-off levels for that test to\n                    recognize patients with non-classical congenital adrenal hyperplasia (NCCAH) and\n                    carriers of clinically relevant mutations in CYP21A2.<\/jats:p><jats:p>\n                    Method and Patients Between July 2006 and July 2015 ACTH-tests were\n                    conducted in 365 children and adolescents (Age 1\u201320\u2009y) suspected\n                    to have NCCAH. As a reference, results from subsequent gene sequencing of\n                        CYP21A2 was used. Inclusion criteria that were used were premature\n                    pubarche with accelerated bone age, hyperandrogenism, hirsutism, or menstrual\n                    irregularities. Receiver operating characteristics (ROC) were plotted. Evaluated\n                    test algorithms were composed around 17OHP measurements by radioimmunoassays.\n                    The most suitable test was identified by the greatest area under the curve\n                    (AUC).<\/jats:p><jats:p>\n                    Results Among the 12 tested algorithms, the sum of 30\u2009min and\n                    60\u2009min stimulated 17OHP values (sum17OHPstim) showed the highest AUC of\n                    0.774 for identifying heterozygous and bi-allelic mutations. A cut-off of\n                    10.1\u2009\u03bcg\/l was advisable. Bi-allelic mutations only were\n                    best identified calculating the difference between 30\u2009min and basal\n                    17OHP values (\u039417OHP30). A cut-off of 9.4\u2009\u03bcg\/l\n                    was most effective.<\/jats:p><jats:p>\n                    Conclusion Alternatively to the above mentioned cut-offs the difference\n                    of 60\u2009min after stimulation to basal 17OHP (\u039417OHP60) can be\n                    used for the benefit of a combined test to identify both heterozygotes and\n                    bi-allelic patients. There are minimal decreases in sensitivity and specificity\n                    compared to an approach that applies two tests. However, it denotes a simpler\n                    approach in the clinical routine.<\/jats:p>","DOI":"10.1055\/a-1217-7169","type":"journal-article","created":{"date-parts":[[2020,8,24]],"date-time":"2020-08-24T22:52:41Z","timestamp":1598309561000},"source":"Crossref","is-referenced-by-count":0,"title":["Establishment of Clinical and Lab Algorithms for the Identification\n                    of Carriers of Mutations in CYP21A2 \u2013 A Study of 365 Children and\n                    Adolescents"],"prefix":"10.1055","author":[{"given":"J.","family":"Meinel","sequence":"additional","affiliation":[{"name":"MVZ Dr. Eberhard & Partner Dortmund (\u00dcBAG), Dortmund\n                    Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"T.","family":"Haverkamp","sequence":"additional","affiliation":[{"name":"MVZ Dr. Eberhard & Partner Dortmund (\u00dcBAG), Dortmund\n                    Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"F.","family":"W\u00fcnsche","sequence":"additional","affiliation":[{"name":"MVZ Dr. Eberhard & Partner Dortmund (\u00dcBAG), Dortmund\n                    Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"A.","family":"Richter-Unruh","sequence":"additional","affiliation":[{"name":"MVZ Dr. Eberhard & Partner Dortmund (\u00dcBAG), Dortmund\n                    Germany"},{"name":"Ruhr-University Bochum, University Children\u2019s Hospital Bochum,\n                    St. Josef- Hospital, Department of Pediatric Endocrinology, Bochum\n                    Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"194","published-online":{"date-parts":[[2020,8,24]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","first-page":"4043","DOI":"10.1210\/jc.2018-01865","article-title":"Congenital adrenal hyperplasia due to steroid 21-hydroxylase deficiency: An\n                   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letters"},{"key":"ref35","doi-asserted-by":"publisher","first-page":"1232","DOI":"10.1055\/s-0041-109717","article-title":"Experts\u2019 Opinion on the Prenatal Therapy of Congenital Adrenal\n                    Hyperplasia (CAH) Due to 21-Hydroxylase Deficiency - Guideline of DGKED in\n                    cooperation with DGGG (S1-Level, AWMF Registry No. 174\/013, July\n                    2015)","volume":"75","author":"H G Dorr","year":"2015","journal-title":"Geburtshilfe Frauenheilkd"}],"container-title":["Experimental and Clinical Endocrinology &amp; Diabetes"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/www.thieme-connect.de\/products\/ejournals\/pdf\/10.1055\/a-1217-7169.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2020,8,24]],"date-time":"2020-08-24T22:53:28Z","timestamp":1598309608000},"score":1,"resource":{"primary":{"URL":"http:\/\/www.thieme-connect.de\/DOI\/DOI?10.1055\/a-1217-7169"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,8,24]]},"references-count":34,"URL":"https:\/\/doi.org\/10.1055\/a-1217-7169","relation":{},"ISSN":["0947-7349","1439-3646"],"issn-type":[{"value":"0947-7349","type":"print"},{"value":"1439-3646","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,8,24]]}}}