{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,12]],"date-time":"2026-11-12T05:01:26Z","timestamp":1794459686109,"version":"4.9.1"},"reference-count":26,"publisher":"Oxford University Press (OUP)","issue":"1","license":[{"start":{"date-parts":[[2025,6,17]],"date-time":"2025-06-17T00:00:00Z","timestamp":1750118400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Diurnal Ltd. UK"},{"name":"Neurocrine UK Ltd."},{"name":"Intramural Research Program of the National Institutes of Health"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025,6,30]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Background<\/jats:title>\n                  <jats:p>Hydrocortisone modified-release hard capsules (MRHC, development name Chronocort) replace the physiological overnight cortisol rise and improve the biochemical control of congenital adrenal hyperplasia (CAH).<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Aim<\/jats:title>\n                  <jats:p>This study aims to evaluate long-term safety, tolerability, and efficacy of MRHC.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>This is an open-label follow-on study.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>Ninety-one patients with classic CAH, mean age 37 years, 68% female, 32% male, entered the study and 22 discontinued. Median treatment duration was 4 years (range 0.2-5.8). Median hydrocortisone dose at study entry was 30\u2005mg\/day and reduced to 20\u2005mg\/day after 24 weeks and stayed stable thereafter until 48 months (P &amp;lt; .0001). Disease control improved on MRHC for the steroid disease markers serum 17-hydroxyprogesterone (17OHP) (P &amp;lt; .03) and androstenedione (A4) (P &amp;lt; .002). After 4 years, the majority of patients had a 17OHP &amp;lt; 4-fold upper limit of normal (ULN) (71%) and an A4 &amp;lt;ULN (90%). Measurement of 17OHP and A4 at 09:00\u2005h and 13:00\u2005h gave similar results. Of the 37 women &amp;lt; 50 years of age who were not on contraceptives over the whole study period, 5 became pregnant (13.5%). Of the men, 13.8% (4\/29) had a partner pregnancy. Seven patients had an adrenal crisis with 1 patient reporting 8 of these giving an incidence of 3.9 crises per 100 patient years.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>Modified-release hard capsule treatment resulted in hydrocortisone dose reduction followed by a stable dose with improved biochemical control associated with fertility. Biochemical control could be reliably monitored by a single blood sample taken between 09:00 and 13:00\u2005h. The incidence of adrenal crises was below that reported previously in patients with CAH.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/ejendo\/lvaf130","type":"journal-article","created":{"date-parts":[[2025,6,27]],"date-time":"2025-06-27T12:17:23Z","timestamp":1751026643000},"page":"76-84","source":"Crossref","is-referenced-by-count":17,"title":["Long-term outcomes in patients with congenital adrenal hyperplasia treated with hydrocortisone modified-release hard capsules"],"prefix":"10.1093","volume":"193","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5106-9719","authenticated-orcid":false,"given":"Wiebke","family":"Arlt","sequence":"first","affiliation":[{"name":"MRC Laboratory of Medical Sciences (MRC LMS) , London W12 0HS ,","place":["United Kingdom"]},{"name":"Imperial College London , Endocrinology, London SW7 2AZ ,","place":["United 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