{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,12,2]],"date-time":"2025-12-02T05:34:39Z","timestamp":1764653679431,"version":"3.46.0"},"reference-count":18,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2025,8,28]],"date-time":"2025-08-28T00:00:00Z","timestamp":1756339200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Clinical Endocrinology"],"published-print":{"date-parts":[[2026,1]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Objective and Background<\/jats:title>\n                    <jats:p>Early identification of adrenal insufficiency (AI) during immune\u2010checkpoint inhibitors (ICIs) is crucial to prevent life\u2010threatening consequences; however, the diagnosis is challenging.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Design, Patients and Measurement<\/jats:title>\n                    <jats:p>In this prospective observational study, ICI\u2010treated cancer patients with morning serum cortisol (SC) within the grey zone (83\u2013414\u2009nmol\/L) were enroled. A low\u2010dose adrenocorticotropic hormone (ACTH) stimulation test was performed to assess peak stimulated SC, preceded by re\u2010evaluation of morning SC. The analysis aimed to refine morning SC cut\u2010offs to minimize the diagnostic grey zone reducing the need for ACTH stimulation. To interpret the results of ACTH test, it was employed both the threshold for peak stimulated SC provided by the Endocrine Society guidelines (500\u2009nmol\/L) and an assay\u2010specific cut\u2010off for the Abbott platform recently proposed in literature (414\u2009nmol\/L). Moreover, the utility of salivary cortisol and cortisone upon awakening was explored.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      In 30 ICI\u2010treated patients, a good positive correlation between morning and peak stimulated SC was confirmed (\n                      <jats:italic>r<\/jats:italic>\n                      \u2009=\u20090.72,\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.001); peak stimulated SC\u2009\u2264\u2009500\u2009nmol\/L and \u2264\u2009414 nmol\/L was detected in 36.7% and 20% of subjects, respectively; all cases were secondary AI. ROC curve analysis identified optimal morning SC thresholds for AI prediction and exclusion (&gt;\u2009196\u2009nmol\/L and \u2264\u2009397\u2009nmol\/L in case of pathological peak stimulated SC\u2009\u2264\u2009500\u2009nmol\/L; &gt;\u2009163\u2009nmol\/L and \u2264\u2009251\u2009nmol\/L in case of pathological peak stimulated SC\u2009\u2264\u2009414\u2009nmol\/L). Salivary cortisol and cortisone upon awakening positively correlated with peak stimulated SC (\n                      <jats:italic>r<\/jats:italic>\n                      \u2009=\u20090.49 and\n                      <jats:italic>r<\/jats:italic>\n                      \u2009=\u20090.56, respectively,\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>Morning SC is a reliable tool for the screening of ICI\u2010related AI; the need for dynamic stimulation would be reduced by the application of assay\u2010specific cut\u2010offs. Salivary hormone analysis of cortisol and cortisone upon awakening may represent a viable alternative in selected cases.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/cen.70023","type":"journal-article","created":{"date-parts":[[2025,8,28]],"date-time":"2025-08-28T13:15:25Z","timestamp":1756386925000},"page":"39-46","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Adrenal Insufficiency During Treatment With Immune\u2010Checkpoint Inhibitors: How to Simplify the Diagnostic Pathway?"],"prefix":"10.1111","volume":"104","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9227-2075","authenticated-orcid":false,"given":"Alice","family":"Nervo","sequence":"first","affiliation":[{"name":"Oncological Endocrinology Unit, AOU Citt\u00e0 della Salute e della Scienza University of Turin Turin Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-5014-8219","authenticated-orcid":false,"given":"Giovanni","family":"Gruosso","sequence":"additional","affiliation":[{"name":"Oncological Endocrinology Unit, AOU Citt\u00e0 della Salute e della Scienza University of Turin Turin Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marta","family":"Marino","sequence":"additional","affiliation":[{"name":"Department of Clinical and Experimental Medicine University of Catania Catania Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Enrica","family":"Migliore","sequence":"additional","affiliation":[{"name":"Cancer Epidemiology Unit University of Turin Turin Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Matteo","family":"Rubiolo","sequence":"additional","affiliation":[{"name":"Oncological Endocrinology Unit, AOU Citt\u00e0 della Salute e della Scienza University of Turin Turin Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Elisa","family":"Vaccaro","sequence":"additional","affiliation":[{"name":"Oncological Endocrinology Unit, AOU Citt\u00e0 della Salute e della Scienza University of Turin Turin Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Emanuela","family":"Arvat","sequence":"additional","affiliation":[{"name":"Oncological Endocrinology Unit, AOU Citt\u00e0 della Salute e della Scienza University of Turin Turin Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2025,8,28]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.intimp.2024.113365"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1210\/er.2018-00006"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1002\/cncr.31200"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1530\/EC-22-0513"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1080\/17446651.2019.1701434"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1530\/EJE-22-0689"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.3390\/curroncol29070370"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1530\/ERC-18-0320"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ctrv.2024.102734"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.critrevonc.2022.103826"},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2016-2118"},{"key":"e_1_2_7_13_1","doi-asserted-by":"publisher","DOI":"10.3390\/endocrines2040044"},{"key":"e_1_2_7_14_1","doi-asserted-by":"publisher","DOI":"10.1210\/jendso\/bvab022"},{"key":"e_1_2_7_15_1","doi-asserted-by":"publisher","DOI":"10.1111\/cen.15074"},{"key":"e_1_2_7_16_1","doi-asserted-by":"publisher","DOI":"10.1056\/evidoa2200182"},{"key":"e_1_2_7_17_1","doi-asserted-by":"publisher","DOI":"10.1530\/EC-18-0068"},{"key":"e_1_2_7_18_1","unstructured":"U.S. Department of Health and Human Services Common Terminology Criteria for Adverse Events (CTCAE) V.5.0(U.S. Department of Health and Human Services 2017) 155 https:\/\/ctep.cancer.gov\/protocoldevelopment\/electronic_applications\/docs\/ctcae_v5_quick_reference_5x7.pdf."},{"key":"e_1_2_7_19_1","doi-asserted-by":"publisher","DOI":"10.1007\/s40618-022-01926-z"}],"container-title":["Clinical Endocrinology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/cen.70023","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,12,2]],"date-time":"2025-12-02T05:34:02Z","timestamp":1764653642000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/cen.70023"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,8,28]]},"references-count":18,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2026,1]]}},"alternative-id":["10.1111\/cen.70023"],"URL":"https:\/\/doi.org\/10.1111\/cen.70023","archive":["Portico"],"relation":{},"ISSN":["0300-0664","1365-2265"],"issn-type":[{"type":"print","value":"0300-0664"},{"type":"electronic","value":"1365-2265"}],"subject":[],"published":{"date-parts":[[2025,8,28]]},"assertion":[{"value":"2025-05-02","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-08-13","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-08-28","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}