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The area-under-the-curve (AUC) of cortisone was computed, and patients were classified as\n                      <jats:italic>GC excess<\/jats:italic>\n                      (AUC above the 90th percentile of controls; Group A) or\n                      <jats:italic>adequate replacement<\/jats:italic>\n                      (10th\u201390th percentile; Group B). Plasma ACTH, copeptin, renin, electrolytes and osmolarity were measured fasting and 120\u00a0min post-dose.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      At baseline, 31.6% of patients showed GC excess, increasing to 36.8% at follow-up. Compared with Group B, Group A exhibited higher HbA1c (46.5 vs. 34.0 mmol\/mol,\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.05) and diastolic blood pressure (84.5\u2009\u00b1\u20098.7 vs. 77.0\u2009\u00b1\u20099.6 mmHg,\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.05) with lower pulse pressure. ACTH and ACTH\/copeptin ratios were markedly reduced in Group A both fasting (median 38.1 vs. 132.4) and post-dose (12.9 vs. 41.6), while renin\/copeptin ratios declined at T1. ACTH\/copeptin correlated inversely with cortisone AUC (\n                      <jats:italic>r<\/jats:italic>\n                      \u2009=\u2009\u2212\u20090.59,\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.01).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Salivary cortisone AUC, together with ACTH\/copeptin and renin\/copeptin ratios, identifies physiologically distinct GC exposure profiles linked to metabolic and haemodynamic alterations. These biomarkers may refine personalised GC replacement in PAI.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1007\/s40618-026-02874-8","type":"journal-article","created":{"date-parts":[[2026,4,24]],"date-time":"2026-04-24T02:51:05Z","timestamp":1776999065000},"page":"1889-1901","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Novel biomarkers to guide glucocorticoid replacement in primary adrenal insufficiency: a proof-of-concept study using copeptin-derived ratios"],"prefix":"10.1007","volume":"49","author":[{"given":"Chiara","family":"Bima","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lorenzo","family":"Campioni","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alessandro Maria","family":"Berton","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chiara","family":"Sola","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Beatrice","family":"Bergoglio","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria Chiara","family":"Di Carlo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Federico","family":"Ponzetto","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fabio","family":"Settanni","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Filippo","family":"Ceccato","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mirko","family":"Parasiliti-Caprino","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8713-3532","authenticated-orcid":false,"given":"Roberta","family":"Giordano","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,4,24]]},"reference":[{"key":"2874_CR1","doi-asserted-by":"publisher","first-page":"19","DOI":"10.1038\/s41572-021-00252-7","volume":"7","author":"S Hahner","year":"2021","unstructured":"Hahner S, Ross RJ, Arlt W, Bancos I, Burger-Stritt S, Torpy DJ et al (2021) Adrenal insufficiency. 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