{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,13]],"date-time":"2026-08-13T08:28:25Z","timestamp":1786609705735,"version":"build-2736575974"},"reference-count":23,"publisher":"Oxford University Press (OUP)","issue":"2","license":[{"start":{"date-parts":[[2026,8,13]],"date-time":"2026-08-13T00:00:00Z","timestamp":1786579200000},"content-version":"vor","delay-in-days":12,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Spanish Society of Endocrinology"},{"DOI":"10.13039\/100011997","name":"FSEEN","doi-asserted-by":"publisher","award":["FIS25\u2014PI050183"],"award-info":[{"award-number":["FIS25\u2014PI050183"]}],"id":[{"id":"10.13039\/100011997","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,8,3]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Importance<\/jats:title>\n                    <jats:p>Adrenal insufficiency (AI) diagnosis is challenging, particularly with indeterminate morning cortisol levels (5-11\u2005\u00b5g\/dL). This study aimed to develop and validate a sex- and age-adjusted dehydroepiandrosterone sulfate (DHEAS)-index to improve AI diagnosis and reduce the need for ACTH stimulation tests.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Design<\/jats:title>\n                    <jats:p>A 2-phase study was conducted. First, a retrospective training cohort of 3.307 DHEAS and morning cortisol measurements from 1.720 adult patients was analyzed to develop sex- and age-specific DHEAS cutoffs. Subsequently, these cutoffs were used to calculate a DHEAS-Index, which was then validated in a prospective external cohort of 71 patients undergoing ACTH stimulation testing for suspected AI.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>In the training cohort, DHEAS levels were significantly lower in patients with morning cortisol &amp;lt;5\u2005\u00b5g\/dL (0.10 [0.10-0.22] \u00b5g\/mL) compared to those with cortisol &amp;gt;5\u2005\u00b5g\/dL (P = .000). Linear regression showed higher morning cortisol, male sex, and younger age were independently associated with higher DHEAS, while older age predicted lower levels (all P = .000). Optimal DHEAS cutoffs, determined by ROC analysis, demonstrated high discriminatory capacity (AUC ranging from 75.2% to 90.5%) for AI across all age and sex subgroups, with men aged 18-29 showing the highest AUC (90.5%). In the validation cohort, the DHEAS-Index achieved a sensitivity of 93% and specificity of 79% for classifying AI (cortisol 60\u2032 &amp;lt; 18\u2005\u00b5g\/dL), with a negative predictive value of 98%. The DHEAS-Index also correlated with the delta increase of cortisol during the ACTH test (rho=0.571, P &amp;lt; .001). Among patients with cortisol values 5-11\u2005\u00b5g\/dL, a DHEAS-Index &amp;gt;1 was associated with a very low probability of AI (5%), whereas a DHEAS-Index &amp;lt;1 increased the likelihood of AI (40%). Finally, a universal DHEAS threshold of &amp;lt;0.2\u2005\u00b5g\/mL yielded 80% sensitivity and 89% specificity, with a 94% negative predictive value, demonstrating the superior performance of the DHEAS-Index.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions and Relevance<\/jats:title>\n                    <jats:p>Age- and sex-adjusted DHEAS thresholds improve screening for adrenal insufficiency diagnosis, reducing unnecessary ACTH testing and enhancing clinical decision-making, particularly in patients with borderline baseline cortisol.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/ejendo\/lvag120","type":"journal-article","created":{"date-parts":[[2026,8,11]],"date-time":"2026-08-11T11:42:16Z","timestamp":1786448536000},"page":"281-292","source":"Crossref","is-referenced-by-count":0,"title":["Development and validation of a sex- and age-adjusted dehydroepiandrosterone sulfate index for suspected adrenal insufficiency"],"prefix":"10.1093","volume":"195","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0373-1573","authenticated-orcid":false,"given":"Arturo","family":"Vega-Beyhart","sequence":"first","affiliation":[{"name":"Endocrinology and Nutrition, Hospital Universitario Ram\u00f3n y Cajal , Madrid 28034 ,","place":["Spain"]},{"name":"Instituto Ram\u00f3n y Cajal de Investigaci\u00f3n Sanitaria (IRYCIS) , Madrid 28034 ,","place":["Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Salas Bravo","sequence":"additional","affiliation":[{"name":"Endocrinology and Nutrition Department, Hospital Clinic , Barcelona 08036 ,","place":["Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mireia","family":"Mora","sequence":"additional","affiliation":[{"name":"Endocrinology and Nutrition Department, Hospital Clinic , Barcelona 08036 ,","place":["Spain"]},{"name":"Fundaci\u00f3 de Recerca Cl\u00ednic Barcelona-Institut 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Biochemistry and Molecular Genetics, Hospital Clinic , Barcelona 08036 ,","place":["Spain"]},{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red de Enfermedades Hep\u00e1ticas y Digestivas (CIBERehd) , Madrid 28029 ,","place":["Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Clara","family":"Sola","sequence":"additional","affiliation":[{"name":"Endocrinology and Nutrition Department, Hospital Clinic , Barcelona 08036 ,","place":["Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karen","family":"Castillo","sequence":"additional","affiliation":[{"name":"Endocrinology and Nutrition Department, Hospital Clinic , Barcelona 08036 ,","place":["Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qiang","family":"Zhao","sequence":"additional","affiliation":[{"name":"Fundaci\u00f3 de Recerca Cl\u00ednic Barcelona-Institut d\u2019Investigacions Biom\u00e8diques August Pi i Sunyer (IDIBAPS) , Barcelona 08036 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Madrid 28029 ,","place":["Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2399-4023","authenticated-orcid":false,"given":"Felicia Alexandra","family":"Hanzu","sequence":"additional","affiliation":[{"name":"Endocrinology and Nutrition Department, Hospital Clinic , Barcelona 08036 ,","place":["Spain"]},{"name":"Fundaci\u00f3 de Recerca Cl\u00ednic Barcelona-Institut d\u2019Investigacions Biom\u00e8diques August Pi i Sunyer (IDIBAPS) , Barcelona 08036 ,","place":["Spain"]},{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red de Diabetes y Enfermedades Metab\u00f3licas Asociadas (CIBERDEM), Instituto de Salud Carlos III (ISCIII) , Madrid 28029 ,","place":["Spain"]},{"name":"Department of Medicine, Faculty of Medicine and Health Sciences, University of Barcelona , Barcelona 08036 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