{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,9,25]],"date-time":"2025-09-25T16:32:17Z","timestamp":1758817937614,"version":"3.37.3"},"reference-count":29,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2015,6,25]],"date-time":"2015-06-25T00:00:00Z","timestamp":1435190400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000265","name":"Medical Research Council, UK","doi-asserted-by":"crossref","award":["G09000001"],"award-info":[{"award-number":["G09000001"]}],"id":[{"id":"10.13039\/501100000265","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Clinical Endocrinology"],"published-print":{"date-parts":[[2016,4]]},"abstract":"<jats:title>Summary<\/jats:title><jats:sec><jats:title>Context<\/jats:title><jats:p>During a clinical trial of regular tetracosactide depot injections, four of 13 patients with autoimmune Addison's disease (AAD) developed adverse reactions immediately following tetracosactide injections. We wished to investigate whether these adverse effects could be due to the production of circulating antitetracosactide (ACTH<jats:sub>1\u201324<\/jats:sub>) antibodies.<\/jats:p><\/jats:sec><jats:sec><jats:title>Design<\/jats:title><jats:p>Anti\u2010ACTH binding activity was investigated using immunoblotting and ELISA on sera from participants in the trial (<jats:italic>n<\/jats:italic>\u00a0=\u00a013; baseline and after tetracosactide exposure), 131 unrelated patients with AAD, 92 patients with Graves\u2019 disease (GD), 15 patients with isolated ACTH deficiency and 102 controls. Immunohistochemistry of human pituitary tissue sections was also performed using pooled sera.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Bands at approximately 4 and 6\u00a0kDa, corresponding to ACTH<jats:sub>1\u201324<\/jats:sub> and full\u2010length ACTH<jats:sub>1\u201339,<\/jats:sub> respectively, were found in 10 of 13 (77%) of sera from trial patients exposed to tetracosactide, including all those who had an adverse reaction. This is in contrast with healthy control sera, which showed no binding. The same 10 subjects also showed high levels of binding to tetracosactide by ELISA, along with 21% of patients with AAD, 14% of patients with GD (both <jats:italic>P<\/jats:italic>\u00a0&lt;\u00a00\u00b7001 compared to controls) and 1 isolated ACTH deficiency patient (7% of 15). These sera also recognized native ACTH in human pituitary sections.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Our study demonstrates that repeated administration of depot tetracosactide can lead to anti\u2010ACTH<jats:sub>1\u201324<\/jats:sub> autoreactivity. In addition, a significant number of patients with AAD and GD also had similar, spontaneous, anti\u2010ACTH reactivity. The presence of these antibodies could mediate some of the adverse effects or explain the well\u2010described phenomenon of resistance to chronic ACTH therapy.<\/jats:p><\/jats:sec>","DOI":"10.1111\/cen.12795","type":"journal-article","created":{"date-parts":[[2015,4,16]],"date-time":"2015-04-16T06:46:36Z","timestamp":1429166796000},"page":"489-495","source":"Crossref","is-referenced-by-count":4,"title":["Spontaneous and tetracosactide\u2010induced anti\u2010ACTH antibodies in man"],"prefix":"10.1111","volume":"84","author":[{"given":"Earn H.","family":"Gan","sequence":"first","affiliation":[{"name":"Institute of Genetic Medicine Newcastle University Newcastle upon Tyne UK"},{"name":"Endocrine Unit Royal Victoria Infirmary Newcastle upon Tyne UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Katie","family":"MacArthur","sequence":"additional","affiliation":[{"name":"Institute of Genetic Medicine Newcastle University Newcastle upon Tyne UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anna L.","family":"Mitchell","sequence":"additional","affiliation":[{"name":"Institute of Genetic Medicine Newcastle University Newcastle upon Tyne UK"},{"name":"Endocrine Unit Royal Victoria Infirmary Newcastle upon Tyne UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Abhijit","family":"Joshi","sequence":"additional","affiliation":[{"name":"Cellular Pathology Department Royal Victoria Infirmary Newcastle upon Tyne UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Patricia","family":"Crock","sequence":"additional","affiliation":[{"name":"John Hunter Children's Hospital University of Newcastle Newcastle NSW Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Simon H. S.","family":"Pearce","sequence":"additional","affiliation":[{"name":"Institute of Genetic Medicine Newcastle University Newcastle upon Tyne UK"},{"name":"Endocrine Unit Royal Victoria Infirmary Newcastle upon Tyne UK"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2015,6,25]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/0165-6147(93)90079-Y"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/0167-5699(96)10008-6"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI29943"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI118513"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2006-2466"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.6362005"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.2337\/diab.35.6.634"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2013-2449"},{"key":"e_1_2_7_10_1","doi-asserted-by":"crossref","first-page":"2970","DOI":"10.1016\/S0021-9258(19)76412-6","article-title":"Adrenocorticotropic hormone: on the structure of human corticotropin","volume":"236","author":"Lee T.H.","year":"1961","journal-title":"Journal of Biological Chemistry"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ygcen.2003.11.005"},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.1038\/211654a0"},{"key":"e_1_2_7_13_1","doi-asserted-by":"publisher","DOI":"10.1136\/ard.30.6.593"},{"key":"e_1_2_7_14_1","doi-asserted-by":"publisher","DOI":"10.1136\/ard.30.6.589"},{"key":"e_1_2_7_15_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI103262"},{"key":"e_1_2_7_16_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI103979"},{"key":"e_1_2_7_17_1","doi-asserted-by":"crossref","first-page":"43","DOI":"10.1182\/blood.V90.1.43.43_43_48","article-title":"Enzyme therapy in Gaucher disease type 1: effect of neutralizing antibodies to acid beta\u2010glucosidase","volume":"90","author":"Ponce E.","year":"1997","journal-title":"Blood"},{"key":"e_1_2_7_18_1","doi-asserted-by":"publisher","DOI":"10.1507\/endocrj1954.34.621"},{"key":"e_1_2_7_19_1","doi-asserted-by":"publisher","DOI":"10.1177\/039463200401700105"},{"key":"e_1_2_7_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/0019-2791(68)90222-X"},{"key":"e_1_2_7_21_1","doi-asserted-by":"crossref","first-page":"78","DOI":"10.1093\/clinchem\/44.1.78","article-title":"Immunoradiometric assay of succinylated corticotropin: an improved method for quantification of ACTH","volume":"44","author":"Kertesz G.","year":"1998","journal-title":"Clinical Chemistry"},{"key":"e_1_2_7_22_1","doi-asserted-by":"publisher","DOI":"10.1136\/bmj.296.6635.1489"},{"key":"e_1_2_7_23_1","doi-asserted-by":"publisher","DOI":"10.1210\/jcem-69-2-231"},{"key":"e_1_2_7_24_1","doi-asserted-by":"publisher","DOI":"10.1210\/jc.77.3.750"},{"key":"e_1_2_7_25_1","doi-asserted-by":"publisher","DOI":"10.1055\/s-2007-973077"},{"key":"e_1_2_7_26_1","first-page":"742","article-title":"Addison's disease: a statistical analysis of five hundred and sixty\u2010six cases and a study of the pathology","volume":"10","author":"Guttman P.H.","year":"1930","journal-title":"Archives of Pathology"},{"key":"e_1_2_7_27_1","doi-asserted-by":"publisher","DOI":"10.1001\/jama.1930.02720140029007"},{"key":"e_1_2_7_28_1","doi-asserted-by":"publisher","DOI":"10.4158\/EP12002.OR"},{"key":"e_1_2_7_29_1","doi-asserted-by":"publisher","DOI":"10.4158\/EP.15.3.220"},{"key":"e_1_2_7_30_1","doi-asserted-by":"publisher","DOI":"10.1210\/jcem-70-5-1391"}],"container-title":["Clinical Endocrinology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2Fcen.12795","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/cen.12795","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,23]],"date-time":"2023-09-23T22:31:26Z","timestamp":1695508286000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/cen.12795"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2015,6,25]]},"references-count":29,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2016,4]]}},"alternative-id":["10.1111\/cen.12795"],"URL":"https:\/\/doi.org\/10.1111\/cen.12795","archive":["Portico"],"relation":{},"ISSN":["0300-0664","1365-2265"],"issn-type":[{"type":"print","value":"0300-0664"},{"type":"electronic","value":"1365-2265"}],"subject":[],"published":{"date-parts":[[2015,6,25]]}}}