{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,20]],"date-time":"2026-09-20T06:20:29Z","timestamp":1789885229882,"version":"4.0.1"},"reference-count":23,"publisher":"Bioscientifica","issue":"5","license":[{"start":{"date-parts":[[2026,2,10]],"date-time":"2026-02-10T00:00:00Z","timestamp":1770681600000},"content-version":"vor","delay-in-days":330,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["journals.bioscientifica.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2025,5,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Recommended treatment for classic congenital adrenal hyperplasia (CAH) in children is hydrocortisone. This therapy is intended to replace cortisol deficiency, but also to reduce the increased production of androgens and their precursors. The aim is to minimize the undesirable side effects of both cortisol deficiency and androgen excess. Short-acting conventional immediate-release hydrocortisone formulations does not mimic physiological diurnal rhythm and often complicate therapy adjustment, mandating frequent administration of often supraphysiological doses, typically 3\u20134 times daily, including nocturnal dosing. To simulate the physiological diurnal cortisol pattern, a delayed- and sustained-release hydrocortisone preparation has been developed and its efficacy was validated through phase 2 and 3 trials in adult patients. Regulatory approval has been extended to encompass both adult and adolescent patients aged 12 years and older. This manuscript aims to provide treatment principles formulated by two expert centers specialized in pediatric CAH therapy regarding the utilization of recently registered hydrocortisone modified-release capsules in the daily management and stress dosing regimen for adolescents with CAH. It elucidates proposed dosing strategies, therapeutic surveillance protocols and the prospective accumulation of data for the assessment of treatment efficacy during childhood.<\/jats:p>","DOI":"10.1530\/ec-24-0619","type":"journal-article","created":{"date-parts":[[2025,3,17]],"date-time":"2025-03-17T09:28:58Z","timestamp":1742203738000},"update-policy":"https:\/\/doi.org\/10.1530\/crossmarkpolicy-10","source":"Crossref","is-referenced-by-count":7,"title":["PERSPECTIVE: Treatment with hydrocortisone modified-release capsules in children and adolescents with congenital adrenal hyperplasia: an expert opinion"],"prefix":"10.1530","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3892-0577","authenticated-orcid":true,"given":"U","family":"Neumann","sequence":"first","affiliation":[{"name":"Charit\u00e9 Universitaetsmedizin Berlin, Clinic for Pediatric Endocrinology and Diabetology 1 , ,","place":["Berlin, Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"O","family":"Blankenstein","sequence":"additional","affiliation":[{"name":"Charit\u00e9 Universitaetsmedizin Berlin, Clinic for Pediatric Endocrinology and Diabetology 1 , ,","place":["Berlin, Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0181-0403","authenticated-orcid":true,"given":"H L","family":"Claahsen-van der Grinten","sequence":"additional","affiliation":[{"name":"Amalia Childrens Hospital, Radboud University Medical Centre, Department of Pediatric Endocrinology 2 , ,","place":["Nijmegen, The Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"416","published-online":{"date-parts":[[2025,3,17]]},"reference":[{"key":"2026070710580990300_bib1","doi-asserted-by":"crossref","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":"2026070710580990300_bib2","doi-asserted-by":"crossref","first-page":"181","DOI":"10.1016\/j.beem.2008.10.014","article-title":"Genetics of congenital adrenal hyperplasia","volume":"23","author":"Krone","year":"2009","journal-title":"Best Pract Res Clin Endocrinol Metab"},{"key":"2026070710580990300_bib3","doi-asserted-by":"crossref","first-page":"4043","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":"2026070710580990300_bib4","doi-asserted-by":"crossref","DOI":"10.3389\/fendo.2022.1064024","article-title":"Challenges in treatment of patients with non-classic congenital adrenal hyperplasia","volume":"13","author":"Adriaansen","year":"2022","journal-title":"Front Endocrinol"},{"key":"2026070710580990300_bib5","doi-asserted-by":"crossref","first-page":"364","DOI":"10.1210\/jc.2015-1710","article-title":"Diagnosis and treatment of primary adrenal insufficiency: an endocrine society clinical practice guideline","volume":"101","author":"Bornstein","year":"2016","journal-title":"J Clin Endocrinol Metab"},{"key":"2026070710580990300_bib6","doi-asserted-by":"crossref","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":"2026070710580990300_bib7","doi-asserted-by":"crossref","first-page":"e1729","DOI":"10.1210\/clinem\/dgaa071","article-title":"Pharmacokinetic\/pharmacodynamic evaluation of hydrocortisone therapy in pediatric patients with congenital adrenal hyperplasia","volume":"105","author":"Melin","year":"2020","journal-title":"J Clin Endocrinol Metab"},{"key":"2026070710580990300_bib8","doi-asserted-by":"crossref","first-page":"e1433","DOI":"10.1210\/clinem\/dgaa626","article-title":"A prospective study of children 0\u20137 Years with cah and adrenal insufficiency treated with hydrocortisone granules","volume":"106","author":"Neumann","year":"2020","journal-title":"J Clin Endocrinol Metab"},{"key":"2026070710580990300_bib9","doi-asserted-by":"crossref","first-page":"3882","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":"2026070710580990300_bib10","doi-asserted-by":"crossref","first-page":"212","DOI":"10.3389\/fendo.2019.00212","article-title":"Cardiovascular health in children and adolescents with congenital adrenal hyperplasia due to 21-hydroxilase deficiency","volume":"10","author":"Improda","year":"2019","journal-title":"Front Endocrinol"},{"key":"2026070710580990300_bib11","first-page":"e5247","article-title":"Cardiovascular disease risk factors and metabolic morbidity in a longitudinal study of congenital adrenal hyperplasia","volume":"106","author":"Torky","year":"2021","journal-title":"J Clin Endocrinol Metab"},{"key":"2026070710580990300_bib12","doi-asserted-by":"crossref","first-page":"500","DOI":"10.3390\/medicina58040500","article-title":"Cardiometabolic health in adolescents and young adults with congenital adrenal hyperplasia","volume":"58","author":"Navardauskaite","year":"2022","journal-title":"Medicina"},{"key":"2026070710580990300_bib13","doi-asserted-by":"crossref","first-page":"1055","DOI":"10.1515\/jpem-2019-0006","article-title":"Long-term follow-up of children with classic congenital adrenal hyperplasia: suggestions for age dependent treatment in childhood and puberty","volume":"32","author":"Pijnenburg-Kleizen","year":"2019","journal-title":"J Pediatr Endocrinol Metab"},{"key":"2026070710580990300_bib14","doi-asserted-by":"crossref","first-page":"554","DOI":"10.1111\/cen.12316","article-title":"An oral multiparticulate, modified-release, hydrocortisone replacement therapy that provides physiological cortisol exposure","volume":"80","author":"Whitaker","year":"2014","journal-title":"Clin Endocrinol"},{"key":"2026070710580990300_bib15","doi-asserted-by":"crossref","first-page":"1137","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":"2026070710580990300_bib16","doi-asserted-by":"crossref","first-page":"1","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 Deliv Transl Res"},{"key":"2026070710580990300_bib17","doi-asserted-by":"crossref","first-page":"R1","DOI":"10.1530\/EJE-21-0794","article-title":"Clinical advances in the pharmacotherapy of congenital adrenal hyperplasia","volume":"186","author":"Prete","year":"2021","journal-title":"Eur J Endocrinol"},{"key":"2026070710580990300_bib18","first-page":"PEP1.1","article-title":"Salivary steroid and 11-oxygenated androgen profiles in patients with congenital adrenal hyperplasia on various glucocorticoid replacement regimens","volume":"73","author":"Auer Mn","year":"2021","journal-title":"Endocr Abstr"},{"key":"2026070710580990300_bib19","doi-asserted-by":"crossref","first-page":"311","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"},{"key":"2026070710580990300_bib20","doi-asserted-by":"crossref","first-page":"441","DOI":"10.1111\/j.1365-2265.2009.03636.x","article-title":"A pharmacokinetic and pharmacodynamic study of delayed- and extended-release hydrocortisone (Chronocort) vs conventional hydrocortisone (Cortef) in the treatment of congenital adrenal hyperplasia","volume":"72","author":"Verma","year":"2010","journal-title":"Clin Endocrinol"},{"key":"2026070710580990300_bib21","doi-asserted-by":"crossref","first-page":"e2063","DOI":"10.1210\/clinem\/dgab051","article-title":"Modified-release hydrocortisone in congenital adrenal hyperplasia","volume":"106","author":"Merke","year":"2021","journal-title":"J Clin Endocrinol Metab"},{"key":"2026070710580990300_bib22","doi-asserted-by":"crossref","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":"2026070710580990300_bib23","doi-asserted-by":"crossref","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"}],"container-title":["Endocrine Connections"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/ec.bioscientifica.com\/view\/journals\/ec\/14\/5\/EC-24-0619.xml","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/ec.bioscientifica.com\/downloadpdf\/journals\/ec\/14\/5\/EC-24-0619.xml","content-type":"text\/html","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/journals.bioscientifica.com\/ec\/article-pdf\/doi\/10.1530\/EC-24-0619\/9411\/ec-24-0619.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/journals.bioscientifica.com\/ec\/article-pdf\/doi\/10.1530\/EC-24-0619\/9411\/ec-24-0619.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,7,7]],"date-time":"2026-07-07T15:22:16Z","timestamp":1783437736000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.bioscientifica.com\/ec\/article\/14\/5\/e240619\/1379\/PERSPECTIVE-Treatment-with-hydrocortisone-modified"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,3,17]]},"references-count":23,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2025,5,1]]}},"URL":"https:\/\/doi.org\/10.1530\/ec-24-0619","relation":{},"ISSN":["2049-3614"],"issn-type":[{"value":"2049-3614","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,3,17]]},"article-number":"e240619"}}