{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,7,30]],"date-time":"2025-07-30T15:51:22Z","timestamp":1753890682252,"version":"3.41.2"},"reference-count":22,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2023,1,10]],"date-time":"2023-01-10T00:00:00Z","timestamp":1673308800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Endocrinol."],"abstract":"<jats:sec><jats:title>Context<\/jats:title><jats:p>The 250\u00b5g-cosyntropin stimulation test (CST) is used to diagnose non-classic congenital adrenal hyperplasia (NCCAH). The current recommendation is to perform CST when follicular 17-hydroxyprogesterone (17OHP) is 6-30 nmol\/L, a cutoff derived from radioimmunoassay (RIA). Recently, enzyme-linked immunosorbent assay (ELISA) has replaced RIA.<\/jats:p><\/jats:sec><jats:sec><jats:title>Objectives<\/jats:title><jats:p>We aimed to (1) determine the RIA and ELISA-based 17OHP cutoffs at which CST should be performed, (2) identify predictors of NCCAH.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>A retrospective study at an Israeli Health Maintenance Organization. Data were retrieved from women with suspected NCCAH, referred for CST during 2001\u20132020. NCCAH was defined as a stimulated 17OHP &amp;gt;30 nmol\/L. Serum 17OHP levels were assayed by RIA from 1\/2000-3\/2015, and by ELISA from 4\/2015-12\/2020. ROC curves were generated and optimal 17OHP thresholds were determined. Multivariate analysis was performed.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>CST was performed in 2409 women (1564 in RIA, 845 in ELISA). NCCAH was diagnosed in 4.7% of the RIA group and 7.5% of the ELISA group. The optimal basal 17OHP cutoff values predicting NCCAH were 6.1 nmol\/L in RIA (sensitivity=93.2%, specificity=91.7%) and 8.2 nmol\/L in ELISA (sensitivity=93.7%, specificity=92.3%). In multivariate analysis, higher basal 17OHP, lower LH: FSH ratio, and oligomenorrhea were predictors of NCCAH in RIA. Higher basal 17OHP, androstenedione, and total testosterone were predictors of NCCAH in ELISA. A lower LH: FSH ratio showed similar trend in ELISA.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Optimal RIA-based basal 17OHP cutoff was comparable with that recommended in guidelines. The results suggest adopting a higher 17OHP cutoff when using ELISA. LH : FSH ratio improves the negative predictive value of basal 17OHP.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fendo.2022.1048663","type":"journal-article","created":{"date-parts":[[2023,1,10]],"date-time":"2023-01-10T20:55:54Z","timestamp":1673384154000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":5,"title":["Screening for non-classic congenital adrenal hyperplasia in women: New insights using different immunoassays"],"prefix":"10.3389","volume":"13","author":[{"given":"Afif","family":"Nakhleh","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Leonard","family":"Saiegh","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Naim","family":"Shehadeh","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Naomi","family":"Weintrob","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mohammad","family":"Sheikh-Ahmad","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lia","family":"Supino-Rosin","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sandra","family":"Alboim","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Raya","family":"Gendelman","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Moshe","family":"Zloczower","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2023,1,10]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2018-01865","article-title":"Congenital adrenal hyperplasia due to steroid 21-hydroxylase deficiency: An endocrine society clinical practice guideline","volume":"103","author":"Speiser","year":"2018","journal-title":"J Clin Endocrinol Metab"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1210\/jcem-69-3-577","article-title":"21-hydroxylase deficiency in female hyperandrogenism: Screening and diagnosis","volume":"69","author":"Azziz","year":"1989","journal-title":"J Clin Endocrinol Metab"},{"key":"B3","unstructured":"17-OH-Progesterone ELISA"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1373\/clinchem.2009.127803","article-title":"Enzyme-linked immunosorbent assay","volume":"56","author":"Engvall","year":"2010","journal-title":"Clin Chem"},{"key":"B5","unstructured":"Escape from ria! comparing the ibl elisa 17 oh progesterone assay with the siemens coat-a-count manual ria assay"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1210\/clinem\/dgaa369","article-title":"Steroid screening tools differentiating nonclassical congenital adrenal hyperplasia and polycystic ovary syndrome","volume":"105","author":"Maffazioli","year":"2020","journal-title":"J Clin Endocrinol Metab"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2008-1582","article-title":"Clinical and molecular characterization of a cohort of 161 unrelated women with nonclassical congenital adrenal hyperplasia due to 21-hydroxylase deficiency and 330 family members","volume":"94","author":"Bidet","year":"2009","journal-title":"J Clin Endocrinol Metab"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1067\/mob.2000.108020","article-title":"21-hydroxylase-deficient nonclassic adrenal hyperplasia is a progressive disorder: a multicenter study","volume":"183","author":"Moran","year":"2000","journal-title":"Am J Obstet Gynecol"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2007-2053","article-title":"A prospective study of the prevalence of nonclassical congenital adrenal hyperplasia among women presenting with hyperandrogenic symptoms and signs","volume":"93","author":"Escobar-Morreale","year":"2008","journal-title":"J Clin Endocrinol Metab"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1530\/EJE-18-0712","article-title":"MANAGEMENT OF ENDOCRINE DISEASE: Diagnosis and management of the patient with non-classic CAH due to 21-hydroxylase deficiency","volume":"180","author":"Nordenstr\u00f6m","year":"2019","journal-title":"Eur J Endocrinol"},{"key":"B11","doi-asserted-by":"publisher","first-page":"397","DOI":"10.1530\/eje.0.1430397","article-title":"Genotype-phenotype associations in non-classical steroid 21-hydroxylase deficiency","volume":"143","author":"Weintrob","year":"2000","journal-title":"Eur J Endocrinol"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.1111\/apa.12147","article-title":"Adult height of subjects with nonclassical 21-hydroxylase deficiency","volume":"102","author":"Eyal","year":"2013","journal-title":"Acta Paediatr"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.2196\/16492","article-title":"Analyzing medical research results based on synthetic data and their relation to real data results: Systematic comparison from five observational studies","volume":"8","author":"Benaim","year":"2020","journal-title":"JMIR Med Inf"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.2337\/dc17-1957","article-title":"Insulin detemir use is associated with higher occurrence of hypoglycemia in hospitalized patients with hypoalbuminemia","volume":"41","author":"Hochberg","year":"2018","journal-title":"Diabetes Care"},{"key":"B15","doi-asserted-by":"publisher","first-page":"A102","DOI":"10.1210\/jendso\/bvab048.204","article-title":"What cut-off value of 17-hydroxyprogesterone should be an indication to perform a 250 \u00b5g cosyntropin stimulation test when NCCAH is suspected? - a retrospective study","volume":"5","author":"Domagala","year":"2021","journal-title":"J Endocr Soc"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM199009273231302","article-title":"Secondary biosynthetic defects in women with late-onset congenital adrenal hyperplasia","volume":"323","author":"Eldar-Geva","year":"2010","journal-title":"N Engl J Med"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.1093\/humupd\/dmx014","article-title":"Non-classic congenital adrenal hyperplasia due to 21-hydroxylase deficiency revisited: an update with a special focus on adolescent and adult women","volume":"23","author":"Carmina","year":"2017","journal-title":"Hum Reprod Update"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.1111\/cen.12935","article-title":"The diagnosis of nonclassic congenital adrenal hyperplasia due to 21-hydroxylase deficiency, based on serum basal or post-ACTH stimulation 17-hydroxyprogesterone, can lead to false-positive diagnosis","volume":"84","author":"Ambroziak","year":"2016","journal-title":"Clin Endocrinol (Oxf)."},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.1210\/jcem.78.4.8157702","article-title":"Clinical review 56: Nonclassic adrenal hyperplasia: current concepts","volume":"78","author":"Azziz","year":"1994","journal-title":"J Clin Endocrinol Metab"},{"key":"B20","doi-asserted-by":"publisher","first-page":"295","DOI":"10.1055\/s-2003-43307","article-title":"21-hydroxylase-deficient nonclassic adrenal hyperplasia: the great pretender","volume":"21","author":"Moran","year":"2003","journal-title":"Semin Reprod Med"},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.1159\/000342179","article-title":"Non-classic adrenal hyperplasia due to the deficiency of 21-hydroxylase and its relation to polycystic ovarian syndrome","volume":"40","author":"Pignatelli","year":"2013","journal-title":"Front Horm Res"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.1210\/jcem-73-3-674","article-title":"Normative data for adrenal steroidogenesis in a healthy pediatric population: age- and sex-related changes after adrenocorticotropin stimulation","volume":"73","author":"Lashansky","year":"1991","journal-title":"J Clin Endocrinol Metab"}],"container-title":["Frontiers in Endocrinology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fendo.2022.1048663\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,1,10]],"date-time":"2023-01-10T20:55:57Z","timestamp":1673384157000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fendo.2022.1048663\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,1,10]]},"references-count":22,"alternative-id":["10.3389\/fendo.2022.1048663"],"URL":"https:\/\/doi.org\/10.3389\/fendo.2022.1048663","relation":{},"ISSN":["1664-2392"],"issn-type":[{"type":"electronic","value":"1664-2392"}],"subject":[],"published":{"date-parts":[[2023,1,10]]},"article-number":"1048663"}}