{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T01:52:48Z","timestamp":1791337968892,"version":"4.3.1"},"reference-count":45,"publisher":"The Endocrine Society","issue":"4","license":[{"start":{"date-parts":[[2021,11,12]],"date-time":"2021-11-12T00:00:00Z","timestamp":1636675200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100009248","name":"Innovatiefonds Zorgverzekeraars","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100009248","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2022,3,24]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Context<\/jats:title>\n                  <jats:p>Hydrocortisone treatment of young patients with 21-hydroxylase deficiency (21OHD) is given thrice daily, but there is debate about the optimal timing of the highest hydrocortisone dose, either mimicking the physiological diurnal rhythm (morning), or optimally suppressing androgen activity (evening).<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Objective<\/jats:title>\n                  <jats:p>We aimed to compare 2 standard hydrocortisone timing strategies, either highest dosage in the morning or evening, with respect to hormonal status throughout the day, nocturnal blood pressure (BP), and sleep and activity scores.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>This 6-week crossover study included 39 patients (aged 4-19 years) with 21OHD. Patients were treated for 3 weeks with the highest hydrocortisone dose in the morning, followed by 3 weeks with the highest dose in the evening (n\u2005=\u200521), or vice versa (n\u2005=\u200518). Androstenedione (A4) and 17-hydroxyprogesterone (17OHP) levels were quantified in saliva collected at 5 am; 7 am; 3 pm; and 11 pm during the last 2 days of each treatment period. The main outcome measure was comparison of saliva 17OHP and A4 levels between the 2 treatment strategies.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>Administration of the highest dose in the evening resulted in significantly lower 17OHP levels at 5 am, whereas the highest dose in the morning resulted in significantly lower 17OHP and A4 levels in the afternoon. The 2 treatment dose regimens were comparable with respect to averaged daily hormone levels, nocturnal BP, and activity and sleep scores.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusion<\/jats:title>\n                  <jats:p>No clear benefit for either treatment schedule was established. Given the variation in individual responses, we recommend individually optimizing dose distribution and monitoring disease control at multiple time points.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1210\/clinem\/dgab826","type":"journal-article","created":{"date-parts":[[2021,11,18]],"date-time":"2021-11-18T00:36:53Z","timestamp":1637195813000},"page":"e1661-e1672","source":"Crossref","is-referenced-by-count":20,"title":["Optimizing the Timing of Highest Hydrocortisone Dose in Children and Adolescents With 21-Hydroxylase Deficiency"],"prefix":"10.1210","volume":"107","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2139-9076","authenticated-orcid":false,"given":"Mariska A M","family":"Schr\u00f6der","sequence":"first","affiliation":[{"name":"Amalia Children\u2019s Hospital, Department of Pediatrics, Radboud University Medical Center, HB Nijmegen, the Netherlands"},{"name":"Department of Laboratory Medicine, Radboud Institute for Molecular Life Sciences (RIMLS), Radboud University Medical Center, HB Nijmegen, the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antonius E","family":"van Herwaarden","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine, Radboud Institute for Molecular Life Sciences (RIMLS), Radboud University Medical Center, HB Nijmegen, the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul N","family":"Span","sequence":"additional","affiliation":[{"name":"Radiotherapy & OncoImmunology Laboratory, Department of Radiation Oncology, Radboud Institute for Molecular Life Sciences (RIMLS), Radboud University Medical Center, HB Nijmegen, the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5352-9328","authenticated-orcid":false,"given":"Erica L T","family":"van den Akker","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Division of Endocrinology, Erasmus MC, University Medical Center Rotterdam, DR Rotterdam, the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2665-8738","authenticated-orcid":false,"given":"Gianni","family":"Bocca","sequence":"additional","affiliation":[{"name":"Beatrix Children\u2019s Hospital, Department of Pediatrics, University Medical Center Groningen, RB Groningen, the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8996-0993","authenticated-orcid":false,"given":"Sabine E","family":"Hannema","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Leiden University Medical Centre, RC Leiden, the Netherlands"},{"name":"Department of Pediatric Endocrinology, Emma Children\u2019s Hospital, Amsterdam UMC, Vrije Universiteit Amsterdam, Amsterdam Gastroenterology Endocrinology Metabolism, MB Amsterdam, the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hetty J","family":"van der Kamp","sequence":"additional","affiliation":[{"name":"Wilhelmina Children\u2019s Hospital, Utrecht University Medical Center, EA Utrecht, the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sandra W K","family":"de Kort","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Haga Teaching Hospital\/Juliana Children\u2019s Hospital, AA The Hague, the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christiaan F","family":"Mooij","sequence":"additional","affiliation":[{"name":"Department of Pediatric Endocrinology, Emma Children\u2019s Hospital, Amsterdam University Medical Centers, University of Amsterdam, AZ Amsterdam, the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dina A","family":"Schott","sequence":"additional","affiliation":[{"name":"Department of Pediatrics Endocrinology, Zuyderland medical center, PC Heerlen, the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Saartje","family":"Straetemans","sequence":"additional","affiliation":[{"name":"Department of Pediatric Endocrinology, Maastricht university medical center, HX Maastricht, the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vera","family":"van Tellingen","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Catharina Hospital, EJ Eindhoven, the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jani\u00eblle A","family":"van der Velden","sequence":"additional","affiliation":[{"name":"Amalia Children\u2019s Hospital, Department of Pediatrics, Radboud University Medical Center, HB Nijmegen, the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fred C G J","family":"Sweep","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine, Radboud Institute for Molecular Life Sciences (RIMLS), Radboud University Medical Center, HB Nijmegen, the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0181-0403","authenticated-orcid":false,"given":"Hedi L","family":"Claahsen-van der Grinten","sequence":"additional","affiliation":[{"name":"Amalia Children\u2019s Hospital, Department of Pediatrics, Radboud University Medical Center, HB Nijmegen, the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"80","published-online":{"date-parts":[[2021,11,12]]},"reference":[{"issue":"8","key":"2022032516102270000_CIT0001","doi-asserted-by":"crossref","first-page":"776","DOI":"10.1056\/NEJMra021561","article-title":"Congenital adrenal hyperplasia","volume":"349","author":"Speiser","year":"2003","journal-title":"N Engl J Med."},{"issue":"3","key":"2022032516102270000_CIT0002","first-page":"245","article-title":"Congenital adrenal hyperplasia due to 21-hydroxylase 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