{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,12]],"date-time":"2026-07-12T02:27:04Z","timestamp":1783823224094,"version":"3.55.0"},"reference-count":67,"publisher":"The Endocrine Society","issue":"12","license":[{"start":{"date-parts":[[2023,6,20]],"date-time":"2023-06-20T00:00:00Z","timestamp":1687219200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100002081","name":"The Irish Research Council","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100002081","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004162","name":"The Meath Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100004162","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100018542","name":"Irish Endocrine Society","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100018542","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Shire Ltd"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2023,11,17]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Background<\/jats:title>\n                  <jats:p>Patients with adrenal insufficiency (AI) require life-long glucocorticoid (GC) replacement therapy. Within tissues, cortisol (F) availability is under the control of the isozymes of 11\u03b2-hydroxysteroid dehydrogenase (11\u03b2-HSD). We hypothesize that corticosteroid metabolism is altered in patients with AI because of the nonphysiological pattern of current immediate release hydrocortisone (IR-HC) replacement therapy. The use of a once-daily dual-release hydrocortisone (DR-HC) preparation, (Plenadren\u00ae), offers a more physiological cortisol profile and may alter corticosteroid metabolism in vivo.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Study Design and Methods<\/jats:title>\n                  <jats:p>Prospective crossover study assessing the impact of 12 weeks of DR-HC on systemic GC metabolism (urinary steroid metabolome profiling), cortisol activation in the liver (cortisone acetate challenge test), and subcutaneous adipose tissue (microdialysis, biopsy for gene expression analysis) in 51 patients with AI (primary and secondary) in comparison to IR-HC treatment and age- and BMI-matched controls.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>Patients with AI receiving IR-HC had a higher median 24-hour urinary excretion of cortisol compared with healthy controls (72.1 \u00b5g\/24 hours [IQR 43.6-124.2] vs 51.9 \u00b5g\/24 hours [35.5-72.3], P = .02), with lower global activity of 11\u03b2-HSD2 and higher 5-alpha reductase activity. Following the switch from IR-HC to DR-HC therapy, there was a significant reduction in urinary cortisol and total GC metabolite excretion, which was most significant in the evening. There was an increase in 11\u03b2-HSD2 activity. Hepatic 11\u03b2-HSD1 activity was not significantly altered after switching to DR-HC, but there was a significant reduction in the expression and activity of 11\u03b2-HSD1 in subcutaneous adipose tissue.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusion<\/jats:title>\n                  <jats:p>Using comprehensive in vivo techniques, we have demonstrated abnormalities in corticosteroid metabolism in patients with primary and secondary AI receiving IR-HC. This dysregulation of pre-receptor glucocorticoid metabolism results in enhanced glucocorticoid activation in adipose tissue, which was ameliorated by treatment with DR-HC.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1210\/clinem\/dgad370","type":"journal-article","created":{"date-parts":[[2023,6,20]],"date-time":"2023-06-20T20:08:08Z","timestamp":1687291688000},"page":"3178-3189","source":"Crossref","is-referenced-by-count":12,"title":["Tissue Glucocorticoid Metabolism in Adrenal Insufficiency: A Prospective Study of Dual-release Hydrocortisone Therapy"],"prefix":"10.1210","volume":"108","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9740-7621","authenticated-orcid":false,"given":"Rosemary A","family":"Dineen","sequence":"first","affiliation":[{"name":"Academic Department of Endocrinology, Beaumont Hospital\/Royal College of Surgeons in Ireland , Dublin, D09 YD60 , 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