{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,16]],"date-time":"2026-05-16T06:36:00Z","timestamp":1778913360000,"version":"3.51.4"},"reference-count":34,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2025,8,17]],"date-time":"2025-08-17T00:00:00Z","timestamp":1755388800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Clinical Endocrinology"],"published-print":{"date-parts":[[2025,12]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>Oral estrogens increase the levels of cortisol binding globulin (CBG) potentially affecting test results for adrenal insufficiency. The objective was to evaluate the influence of oral and transdermal estradiol on total plasma (p) and salivary cortisol in hypogonadal women with secondary adrenal insufficiency or at risk of developing adrenal insufficiency. Furthermore, to determine if estradiol treatment can lead to a change in the diagnosis of adrenal insufficiency based on a Synacthen\u2010test.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Crossover study. Intervention: 12 weeks oral estradiol (2\u2009mg), 12 weeks transdermal estradiol (100\u2009\u00b5g\/day), and 12 weeks without estradiol. After each intervention plasma total cortisol (pTC), salivary cortisol and CBG were measured before and after a 250 ug Synacthen\u2010test (30\u2009min) (normal response pTC\u2009&gt;\u2009420\u2009nmol\/L, overt adrenal insufficiency pTC\u2009&lt;\u2009250\u2009nmol\/L).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Seventeen hypopituitary patients, mean age 42\u2009\u00b1\u20096 years were included. 30\u2010min pTC did not change significantly according to intervention (no estradiol 401 (interquartile range: 55\u2013495), oral estradiol 440 (74\u2013600), and transdermal estradiol 304 (48\u2013492) nmol\/L). Based on pTC no patients with overt adrenal insufficiency crossed the cut\u2010off for adrenal insufficiency between interventions whereas three patients with borderline adrenal insufficiency (pTC 390\u2013559\u2009nmol\/L) crossed the cut\u2010off. CBG was higher on oral estradiol compared to no estradiol (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.001) and transdermal estradiol (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.017) whereas 30\u2010min salivary cortisol was lower on oral estradiol compared to no estradiol (6.6 (1.6\u201323.0) vs. 10.4 (3.6\u201325.5\u2009nmol\/L)\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.04) and transdermal estradiol (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.07).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>In patients with overt adrenal insufficiency pTC was not influenced by estradiol supplementation. However, salivary cortisol decreased on oral estradiol concomitant with an increase in CBG levels. Our data may support the use of transdermal estradiol and the use of salivary cortisol when evaluating the adrenal axis.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/cen.70020","type":"journal-article","created":{"date-parts":[[2025,8,18]],"date-time":"2025-08-18T06:57:23Z","timestamp":1755500243000},"page":"852-862","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Significance of Exogenous Estradiol on Plasma Cortisol and Salivary Cortisol During Adrenocorticotropic Hormone Stimulation in Women With Pituitary Insufficiency"],"prefix":"10.1111","volume":"103","author":[{"given":"Laura S.","family":"Aagaard","sequence":"first","affiliation":[{"name":"Department of Nephrology and Endocrinology Rigshospitalet Copenhagen Copenhagen Denmark"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4834-6724","authenticated-orcid":false,"given":"Jesper","family":"Krogh","sequence":"additional","affiliation":[{"name":"Department of Medicine, Clinic for Pituitary Disorders Zealand University Hospital Koge Denmark"},{"name":"Department of Clinical Medicine Copenhagen University Copenhagen Denmark"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Signe","family":"Perlman","sequence":"additional","affiliation":[{"name":"Department of Gynecology (SP) North Zealand Hospital Hiller\u00f8d Denmark"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marianne","family":"Klose","sequence":"additional","affiliation":[{"name":"Department of Nephrology and Endocrinology Rigshospitalet Copenhagen Copenhagen Denmark"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1656-3516","authenticated-orcid":false,"given":"Mikkel","family":"Andreassen","sequence":"additional","affiliation":[{"name":"Department of Nephrology and Endocrinology Rigshospitalet Copenhagen Copenhagen Denmark"},{"name":"Department of Clinical Medicine Copenhagen University Copenhagen Denmark"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2025,8,17]]},"reference":[{"key":"e_1_2_6_2_1","doi-asserted-by":"publisher","DOI":"10.1111\/cen.12680"},{"key":"e_1_2_6_3_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1478-3231.2010.02431.x"},{"key":"e_1_2_6_4_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2265.2007.02784.x"},{"key":"e_1_2_6_5_1","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2005-0352"},{"key":"e_1_2_6_6_1","doi-asserted-by":"publisher","DOI":"10.1210\/jcem-27-10-1463"},{"key":"e_1_2_6_7_1","doi-asserted-by":"publisher","DOI":"10.1097\/gme.0b013e31803867a"},{"key":"e_1_2_6_8_1","doi-asserted-by":"publisher","DOI":"10.1080\/09513590902836551"},{"key":"e_1_2_6_9_1","doi-asserted-by":"publisher","DOI":"10.3803\/EnM.2022.1549"},{"key":"e_1_2_6_10_1","doi-asserted-by":"publisher","DOI":"10.1210\/clinem\/dgad576"},{"key":"e_1_2_6_11_1","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2007-0181"},{"key":"e_1_2_6_12_1","doi-asserted-by":"publisher","DOI":"10.1177\/0004563216687335"},{"key":"e_1_2_6_13_1","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2015-1710"},{"key":"e_1_2_6_14_1","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/S2173-5093(14)70069-8","article-title":"Guidelines for Diagnosis and Treatment of Adrenal Insufficiency in Adults","volume":"61","author":"Miguel Novoa P. de","year":"2014","journal-title":"Endocrinologia y nutrici\u00f3n (English ed)"},{"key":"e_1_2_6_15_1","unstructured":"D.ErskineandH.Simpson \u201cSociety for Endocrinology.\u201d Exogenous Steroids Treatment in Adults: Adrenal Insufficiency and Adrenal Crisis\u2014Who Is at Risk and How Should They Be Managed Safely. 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