{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,7]],"date-time":"2026-07-07T06:20:39Z","timestamp":1783405239796,"version":"3.54.6"},"reference-count":29,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,7,7]],"date-time":"2026-07-07T00:00:00Z","timestamp":1783382400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100002839","name":"Charit\u00e9-Universit\u00e4tsmedizin Berlin","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100002839","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Endocrinol."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>\n                      Replacement therapy for congenital adrenal hyperplasia (CAH) in childhood includes hydrocortisone and, in salt-wasting forms, addition of fludrocortisone. Immediate-release hydrocortisone often fails to adequately suppress early morning 17-hydroxyprogesterone (17OHP) levels. Hydrocortisone modified-release capsules (HMRC, Efmody\n                      <jats:sup>\u00ae<\/jats:sup>\n                      ) were approved by the EMA in 2021 for the treatment of patients aged \u226512 years with CAH. This study evaluates the efficacy and safety of HMRC in children and adolescents based on real-world data collected from the I-CAH registry.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      A single-center retrospective analysis of children with CAH was conducted. Linear mixed models (LMMs) were used to calculate pre\u2013post comparisons of 17OHP saliva profiles, growth rate, bone age, body mass index, hydrocortisone and fludrocortisone dosage, blood pressure, and safety parameters before and during HMRC therapy (study registration,\n                      <jats:ext-link>https:\/\/drks.de\/search\/de<\/jats:ext-link>\n                      , DRKS00038319).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Findings<\/jats:title>\n                    <jats:p>The median age of the 36 children with CAH at the time of treatment switching to HMRC was 10 years (interquartile range [IQR]: 8\u201314 years). Of these, 15 were prepubertal and 21 were (post)pubertal. HMRC therapy was associated with a deceleration of previously increased growth velocity (pre-switch: 0.1 SDS\/year, 95% CI: 0.0 to 0.2; post-switch: -0.1 SDS\/year, 95% CI: \u20130.2 to 0.1) and with a reduction of median difference of bone age and chronological age by 0.50 years (IQR -1.17\u20130.27, range -2.2\u20132.00). Mean hydrocortisone dose increased by 2.4 mg\/m\u00b2\/day during HMRC treatment. Mean morning 17OHP concentrations significantly decreased from 337 ng\/L (95% CI: 240\u2013437) to 214 ng\/L (95% CI: 155\u2013294) after switching to HMRC treatment. No adrenal crisis was observed.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Interpretation<\/jats:title>\n                    <jats:p>Twice-daily HMRC therapy can also improve CAH therapy in children and adolescents in terms of hormonal control and growth.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fendo.2026.1854737","type":"journal-article","created":{"date-parts":[[2026,7,7]],"date-time":"2026-07-07T05:45:59Z","timestamp":1783403159000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Modified-release hydrocortisone (Efmody\u00ae) in children with congenital adrenal hyperplasia: a retrospective registry study"],"prefix":"10.3389","volume":"17","author":[{"given":"Erwin","family":"Lankes","sequence":"first","affiliation":[{"name":"Department of Pediatric Endocrinology and Diabetology, Charit\u00e9 - Universit\u00e4tsmedizin Berlin, ENDO-ERN Center","place":["Berlin, Germany"]},{"name":"Center for Chronic Sick Children, Charit\u00e9 - Universit\u00e4tsmedizin Berlin","place":["Berlin, Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Levin","family":"Wiebelt","sequence":"additional","affiliation":[{"name":"Institute of Biometry and Clinical Epidemiology, Charit\u00e9 \u2013 Universit\u00e4tsmedizin Berlin","place":["Berlin, Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kathrin Bettina","family":"Helge","sequence":"additional","affiliation":[{"name":"Department of Pediatric Endocrinology and Diabetology, Charit\u00e9 - Universit\u00e4tsmedizin Berlin, ENDO-ERN Center","place":["Berlin, Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dirk","family":"Schnabel","sequence":"additional","affiliation":[{"name":"Department of Pediatric Endocrinology and Diabetology, Charit\u00e9 - Universit\u00e4tsmedizin Berlin, ENDO-ERN Center","place":["Berlin, Germany"]},{"name":"Center for Chronic Sick Children, Charit\u00e9 - Universit\u00e4tsmedizin Berlin","place":["Berlin, Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter","family":"K\u00fchnen","sequence":"additional","affiliation":[{"name":"Department of Pediatric Endocrinology and Diabetology, Charit\u00e9 - Universit\u00e4tsmedizin Berlin, ENDO-ERN Center","place":["Berlin, Germany"]},{"name":"German Center for Child and Adolescent Health (DZKJ), Partner Site Berlin","place":["Berlin, Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Oliver","family":"Blankenstein","sequence":"additional","affiliation":[{"name":"Department of Pediatric Endocrinology and Diabetology, Charit\u00e9 - Universit\u00e4tsmedizin Berlin, ENDO-ERN Center","place":["Berlin, Germany"]},{"name":"Center for Chronic Sick Children, Charit\u00e9 - Universit\u00e4tsmedizin Berlin","place":["Berlin, Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Uta","family":"Neumann","sequence":"additional","affiliation":[{"name":"Department of Pediatric Endocrinology and Diabetology, Charit\u00e9 - Universit\u00e4tsmedizin Berlin, ENDO-ERN Center","place":["Berlin, Germany"]},{"name":"Center for Chronic Sick Children, Charit\u00e9 - Universit\u00e4tsmedizin Berlin","place":["Berlin, Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,7,7]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"91","DOI":"10.1210\/endrev\/bnab016","article-title":"Congenital adrenal hyperplasia-current insights in pathophysiology, diagnostics, and management","volume":"43","author":"Claahsen-van der Grinten","year":"2022","journal-title":"Endocr Rev"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1530\/ey.16.8.5","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":"B3","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2009-0942","article-title":"Hydrocortisone dosing during puberty in patients with classical congenital adrenal hyperplasia: an evidence-based recommendation","volume":"94","author":"Bonfig","year":"2009","journal-title":"J Clin Endocrinol Metab"},{"key":"B4","doi-asserted-by":"publisher","first-page":"84","DOI":"10.1159\/000071876","article-title":"Growth analysis in patients with 21-hydroxylase deficiency influence of glucocorticoid dosage, age at diagnosis, phenotype and genotype on growth and height outcome","volume":"60","author":"Grigorescu-Sido","year":"2003","journal-title":"Hormone Res"},{"key":"B5","doi-asserted-by":"publisher","first-page":"199","DOI":"10.1136\/archdischild-2015-309538","article-title":"Is physiological glucocorticoid replacement important in children","volume":"102","author":"Porter","year":"2017","journal-title":"Arch Dis Child"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1210\/clinem\/dgaa626","article-title":"A prospective study of children 0-7 years with cah and adrenal insufficiency treated with hydrocortisone granules","volume":"106","author":"Neumann","year":"2020","journal-title":"J Clin Endocrinol Metab"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1530\/ey.18.8.3","article-title":"Modified-release hydrocortisone in congenital adrenal hyperplasia","volume":"106","author":"Merke","year":"2021","journal-title":"J Clin Endocrinol Metab"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1111\/cen.14976","article-title":"Developing oral chronotherapy for cortisol replacement in congenital adrenal hyperplasia","volume":"101","author":"Whitaker","year":"2023","journal-title":"Clin Endocrinol (Oxf)"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1007\/s13346-022-01183-w","article-title":"Chronotherapy based on modified-release hydrocortisone to restore the physiological cortisol diurnal rhythm","volume":"13","author":"Whitaker","year":"2022","journal-title":"Drug Delivery Transl Res"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejps.2021.105913","article-title":"Development and verification of an endogenous PBPK model to inform hydrocortisone replacement dosing in children and adults with cortisol deficiency","volume":"165","author":"Bonner","year":"2021","journal-title":"Eur J Pharm Sci"},{"key":"B11","doi-asserted-by":"publisher","first-page":"4405","DOI":"10.3390\/ijms20184405","article-title":"The role of international databases in understanding the aetiology and consequences of differences\/disorders of sex development","volume":"20","author":"Ali","year":"2019","journal-title":"Int J Mol Sci"},{"key":"B12","first-page":"A5536","article-title":"Riva-Rocci and blood pressure","volume":"157","author":"van Gijn","year":"2013","journal-title":"Ned Tijdschr Geneeskd"},{"key":"B13","article-title":"Referenzperzentile f\u00fcr anthropometrische Ma\u00dfzahlen und Blutdruck aus der Studie zur Gesundheit von Kindern und Jugendlichen in Deutschland (KiGGS)","author":"Neuhauser","year":"2013"},{"key":"B14","volume-title":"Radiograph Atlas of Skeletal Development of the Hand and Wrist","author":"Greulich","year":"1959"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.1530\/ec-24-0619","article-title":"Perspective: Treatment with hydrocortisone modified-release capsules in children and adolescents with congenital adrenal hyperplasia: an expert opinion","volume":"14","author":"Neumann","year":"2025","journal-title":"Endocr Connect"},{"key":"B16","volume-title":"Tanner stages","author":"Emmanuel","year":"2025"},{"key":"B17","article-title":"_emmeans: Estimated Marginal Means, aka Least-Squares Means. R package version 1.10.62024","author":"Lenth","year":""},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.18637\/jss.v082.i13","article-title":"lmerTest package: Tests in linear mixed effects models","volume":"82","author":"Kuznetsova","year":"2017","journal-title":"J Stat Software"},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.1159\/000069321","article-title":"The calculation of target height reconsidered","volume":"59","author":"Hermanussen","year":"2003","journal-title":"Horm Res"},{"key":"B20","article-title":"R: A language and environment for statistical computing","year":"2021"},{"key":"B21","article-title":"dplyr: A Grammar of Data Manipulation. R package version 1.1.42023","author":"Wickham","year":"2023"},{"key":"B22","doi-asserted-by":"publisher","first-page":"1","DOI":"10.18637\/jss.v040.i03","article-title":"Dates and times made easy with lubridate","volume":"40","author":"Grolemund","year":"2011","journal-title":"J Stat Software"},{"key":"B23","article-title":"merTools: Tools for Analyzing Mixed Effect Regression Models_. R package version 0.6.2. 2024","author":"Knowles","year":""},{"key":"B24","doi-asserted-by":"crossref","DOI":"10.1007\/978-3-319-24277-4","volume-title":"Ggplot2: Elegant Graphics for Data Analysis","author":"Wickham","year":"2016"},{"key":"B25","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2014-3809","article-title":"A phase 2 study of chronocort, a modified-release formulation of hydrocortisone, in the treatment of adults with classic congenital adrenal hyperplasia","volume":"100","author":"Mallappa","year":"2015","journal-title":"J Clin Endocrinol Metab"},{"key":"B26","doi-asserted-by":"publisher","first-page":"39","DOI":"10.1097\/med.0000000000000308","article-title":"Growth and development in children with classic congenital adrenal hyperplasia","volume":"24","author":"Bonfig","year":"2017","journal-title":"Curr Opin Endocrinol Diabetes Obes"},{"key":"B27","doi-asserted-by":"publisher","first-page":"80","DOI":"10.1210\/endrev\/bnae026","article-title":"Cardiometabolic aspects of congenital adrenal hyperplasia","volume":"46","author":"Krysiak","year":"2025","journal-title":"Endocr Rev"},{"key":"B28","doi-asserted-by":"publisher","first-page":"lvac006","DOI":"10.1093\/ejendo\/lvac006","article-title":"Modified-release hydrocortisone is associated with lower plasma renin activity in patients with salt-wasting congenital adrenal hyperplasia","volume":"188","author":"Tschaidse","year":"2023","journal-title":"Eur J Endocrinol"},{"key":"B29","doi-asserted-by":"publisher","DOI":"10.6065\/apem.2346094.047","article-title":"The impacts of COVID-19 on childhood obesity: prevalence, contributing factors, and implications for management","volume":"29","author":"Kim","year":"2024","journal-title":"Ann Pediatr Endocrinol Metab"}],"container-title":["Frontiers in Endocrinology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fendo.2026.1854737\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,7,7]],"date-time":"2026-07-07T05:46:00Z","timestamp":1783403160000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fendo.2026.1854737\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,7,7]]},"references-count":29,"alternative-id":["10.3389\/fendo.2026.1854737"],"URL":"https:\/\/doi.org\/10.3389\/fendo.2026.1854737","relation":{},"ISSN":["1664-2392"],"issn-type":[{"value":"1664-2392","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,7,7]]},"article-number":"1854737"}}