{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,26]],"date-time":"2026-08-26T22:56:36Z","timestamp":1787784996595,"version":"build-2784847793"},"reference-count":40,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2026,4,28]],"date-time":"2026-04-28T00:00:00Z","timestamp":1777334400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,4,28]],"date-time":"2026-04-28T00:00:00Z","timestamp":1777334400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Clinical Endocrinology"],"published-print":{"date-parts":[[2026,9]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>Adrenal insufficiency's (AI) lifelong replacement therapy by conventional glucocorticoid (GC) regimens poorly mimics physiological cortisol, leading to poor adherence and metabolic abnormalities. Modified\u2010release hydrocortisone (MR\u2010HC) provides a more physiological cortisol replacement with potentially enhanced outcomes. This study assessed comparative evidence of MR\u2010HC versus GC in patients with AI.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Design<\/jats:title>\n                    <jats:p>Systematic review and meta\u2010analysis.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Comparative articles published until July 2025 were searched in PubMed, Scopus and Web of Science. Glucose metabolism, anthropometrics, lipid profile and blood pressure were the primary outcomes; bone health parameters and safety and tolerability measures were secondary outcomes.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Across six included studies (\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u2009400), MR\u2010HC was associated with significant reductions in BMI (mean difference \u22121.1, 95% CI \u22122.11 to \u22120.1) and waist circumference (\u22125.03, 95% CI\u22128.54 to \u22121.51), without significant changes in body weight. MR\u2010HC lowered total cholesterol (\u221210.64, 95% CI \u221219.86 to \u22121.42), systolic blood pressure (\u22126.03, 95% CI \u221210.95 to \u22121.1) and diastolic blood pressure (\u22124.35, 95% CI \u22127.37 to \u22121.34). Glucose metabolic outcomes (fasting glucose and HbA1c) did not differ significantly between the groups, but sensitivity analysis suggested a potential HbA1c benefit with MR\u2010HC. Bone health results favoured MR\u2010HC for lumbar spine\n                      <jats:italic>T<\/jats:italic>\n                      \u2010score (0.69, 95% CI 0.16 to 1.22), and femoral neck\n                      <jats:italic>T<\/jats:italic>\n                      \u2010score (0.64, 95% CI 0.16 to 1.12). Safety measures favoured MR\u2010HC for Infection score (\u22121.7, 95% CI \u22122.6 to \u22120.8), and flu\u2010like events (\u22121.0, 95% CI \u22121.6 to \u22120.4), but not vertebral fractures (0.20, 95% CI 0.03 to 1.55), or AddiQol score (4.00, 95% CI \u22120.68 to 8.68).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>MR\u2010HC demonstrated improved effects on anthropometric measures, lipid profile, blood pressure, bone mineral density, and safety and tolerability compared to conventional GC with no apparent differences in glucose metabolism. These findings validate MR\u2010HC as a better regimen, but await larger long\u2010term trials for confirmation.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Trial Registration<\/jats:title>\n                    <jats:p>\n                      This study was prospectively registered on PROSPERO (CRD420251074980). Available at:\n                      <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"http:\/\/www.crd.york.ac.uk\/PROSPERO\/view\/CRD420251074980\">https:\/\/www.crd.york.ac.uk\/PROSPERO\/view\/CRD420251074980<\/jats:ext-link>\n                      .\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/cen.70149","type":"journal-article","created":{"date-parts":[[2026,4,29]],"date-time":"2026-04-29T03:16:38Z","timestamp":1777432598000},"page":"285-297","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Metabolic Effects of Modified\u2010Release Hydrocortisone Versus Short Acting Conventional Oral Glucocorticoids in Adrenal Insufficiency: A Systematic Review and Meta\u2010Analysis"],"prefix":"10.1111","volume":"105","author":[{"ORCID":"https:\/\/orcid.org\/0009-0000-7714-4182","authenticated-orcid":false,"given":"Mohammad Ehab","family":"Abdelsattar","sequence":"first","affiliation":[{"name":"Faculty of Medicine Alexandria University Alexandria Egypt"},{"name":"Medical Research Group of Egypt (MRGE) Negida Academy Arlington Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mai","family":"Abdallah","sequence":"additional","affiliation":[{"name":"Medical Research Group of Egypt (MRGE) Negida Academy Arlington Massachusetts USA"},{"name":"Faculty of Medicine Mansoura University Mansoura Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ola","family":"Khaled","sequence":"additional","affiliation":[{"name":"Medical Research Group of Egypt (MRGE) Negida Academy Arlington Massachusetts USA"},{"name":"Faculty of Medicine Zagazig University Sharkia Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Heba","family":"Aboeldahab","sequence":"additional","affiliation":[{"name":"Medical Research Group of Egypt (MRGE) Negida Academy Arlington Massachusetts USA"},{"name":"Clinical Research Department El\u2010Gomhoria General Hospital, MOHP Alexandria Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nour Mohyeldin","family":"Ahmed","sequence":"additional","affiliation":[{"name":"Faculty of Medicine Alexandria University Alexandria Egypt"},{"name":"Medical Research Group of Egypt (MRGE) Negida Academy Arlington Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yusuf","family":"Abdeen","sequence":"additional","affiliation":[{"name":"Medical Research Group of Egypt (MRGE) Negida Academy Arlington Massachusetts USA"},{"name":"Faculty of Medicine Al\u2010Azhar University Cairo Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nada","family":"Altayeb","sequence":"additional","affiliation":[{"name":"Medical Research Group of Egypt (MRGE) Negida Academy Arlington Massachusetts USA"},{"name":"Faculty of Medicine Mansoura University Mansoura Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yousef","family":"Mousa","sequence":"additional","affiliation":[{"name":"Medical Research Group of Egypt (MRGE) Negida Academy Arlington Massachusetts USA"},{"name":"Faculty of Medicine Al\u2010Azhar University Cairo Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ahmed Gaballa","family":"Ali","sequence":"additional","affiliation":[{"name":"Faculty of Medicine Alexandria University Alexandria Egypt"},{"name":"Medical Research Group of Egypt (MRGE) Negida Academy Arlington Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohammed Tarek","family":"Hasan","sequence":"additional","affiliation":[{"name":"Medical Research Group of Egypt (MRGE) Negida Academy Arlington Massachusetts USA"},{"name":"Faculty of Medicine Al\u2010Azhar University Cairo Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,4,28]]},"reference":[{"key":"e_1_2_13_2_1","volume-title":"Endotext [Internet]","author":"Alexandraki K.","year":"2000"},{"key":"e_1_2_13_3_1","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2015-1710"},{"key":"e_1_2_13_4_1","doi-asserted-by":"publisher","DOI":"10.3803\/EnM.2024.1894"},{"key":"e_1_2_13_5_1","volume-title":"StatPearls [Internet]","author":"Huecker M. 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