{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,10]],"date-time":"2026-10-10T02:06:19Z","timestamp":1791597979201,"version":"4.3.4"},"reference-count":30,"publisher":"The Endocrine Society","issue":"8","license":[{"start":{"date-parts":[[2020,6,2]],"date-time":"2020-06-02T00:00:00Z","timestamp":1591056000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"funder":[{"name":"The Children\u2019s Hospital Charity","award":["CA09018"],"award-info":[{"award-number":["CA09018"]}]},{"name":"The Children\u2019s Hospital Charity","award":["CA110916"],"award-info":[{"award-number":["CA110916"]}]},{"DOI":"10.13039\/501100000265","name":"Medical Research Council","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100000265","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000691","name":"Academy of Medical Sciences","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100000691","id-type":"DOI","asserted-by":"publisher"}]},{"name":"British Society for Paediatric Endocrinology and Diabetes"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2020,8,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Context<\/jats:title>\n                  <jats:p>The Short Synacthen Test (SST) is the gold standard for diagnosing adrenal insufficiency. It requires invasive administration of Synacthen, venous sampling, and is resource-intensive.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Objective<\/jats:title>\n                  <jats:p>To develop a nasally administered SST, with salivary glucocorticoids measurement, to assess the adrenal response.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Design<\/jats:title>\n                  <jats:p>We conducted 5 studies: 4 open-label, sequence-randomized, crossover, pharmacodynamic studies testing 6 doses\/formulations and a repeatability study. Additionally, pharmacokinetic analysis was undertaken using our chosen formulation, 500 \u00b5g tetracosactide with mucoadhesive chitosan, Nasacthin003, in our pediatric study.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Setting<\/jats:title>\n                  <jats:p>Adult and children\u2019s clinical research facilities.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Participants<\/jats:title>\n                  <jats:p>A total of 36 healthy adult males and 24 healthy children.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Intervention<\/jats:title>\n                  <jats:p>We administered all 6 nasal formulations using an European regulator endorsed atomization device. The IV comparators were 250 \u00b5g or 1 \u00b5g SST.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Main Outcome Measures<\/jats:title>\n                  <jats:p>We analyzed paired blood and saliva samples for plasma cortisol and salivary cortisol and cortisone.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>The addition of chitosan to tetracosactide and dose escalation increased peak cortisol response (P\u2005=\u20050.01 and 0.001, respectively). The bioavailability of Nasacthin003 was 14.3%. There was no significant difference in plasma cortisol at 60 minutes between 500 \u00b5g Nasacthin003 and 250 \u00b5g IV Synacthen (P\u2005=\u20050.17). The repeatability coefficient at 60 minutes was 105 nmol\/L for IV Synacthen and salivary cortisol and cortisone was 10.3 and 21.1 nmol\/L, respectively. The glucocorticoid response in children was indistinguishable from that of adults.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>Nasal administration of Nasacthin003 generates equivalent plasma cortisol values to the 250-\u00b5g IV SST and, with measurement at 60 minutes of salivary cortisol or cortisone, provides a noninvasive test for adrenal insufficiency.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1210\/clinem\/dgaa323","type":"journal-article","created":{"date-parts":[[2020,6,2]],"date-time":"2020-06-02T19:14:44Z","timestamp":1591125284000},"page":"2692-2703","source":"Crossref","is-referenced-by-count":16,"title":["Pharmacodynamic studies of nasal tetracosactide with salivary glucocorticoids for a noninvasive Short Synacthen Test"],"prefix":"10.1210","volume":"105","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2390-5593","authenticated-orcid":false,"given":"Charlotte J","family":"Elder","sequence":"first","affiliation":[{"name":"Department of Oncology and Metabolism, The University of Sheffield, Sheffield, United Kingdom"},{"name":"Department of Endocrinology, Sheffield Children\u2019s NHS Foundation Trust, Sheffield, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruben","family":"Vilela","sequence":"additional","affiliation":[{"name":"Department of Oncology and Metabolism, The University of Sheffield, Sheffield, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Trevor N","family":"Johnson","sequence":"additional","affiliation":[{"name":"Certara UK Limited, Sheffield, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rosie N","family":"Taylor","sequence":"additional","affiliation":[{"name":"Statistical Services Unit, The University of Sheffield, Sheffield, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0313-8916","authenticated-orcid":false,"given":"E Helen","family":"Kemp","sequence":"additional","affiliation":[{"name":"Department of Oncology and Metabolism, The University of Sheffield, Sheffield, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brian G","family":"Keevil","sequence":"additional","affiliation":[{"name":"Department of Clinical Biology, Manchester University NHS Trust, Manchester, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexandra S","family":"Cross","sequence":"additional","affiliation":[{"name":"Department of Oncology and Metabolism, The University of Sheffield, Sheffield, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9222-9678","authenticated-orcid":false,"given":"Richard J","family":"Ross","sequence":"additional","affiliation":[{"name":"Department of Oncology and Metabolism, The University of Sheffield, Sheffield, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Neil P","family":"Wright","sequence":"additional","affiliation":[{"name":"Department of Endocrinology, Sheffield Children\u2019s NHS Foundation Trust, Sheffield, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"80","published-online":{"date-parts":[[2020,6,2]]},"reference":[{"issue":"2","key":"2021122110512233200_CIT0001","doi-asserted-by":"crossref","first-page":"364","DOI":"10.1210\/jc.2015-1710","article-title":"Diagnosis and treatment of primary adrenal insufficiency: an Endocrine Society Clinical Practice 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