{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,16]],"date-time":"2026-02-16T09:06:12Z","timestamp":1771232772299,"version":"3.50.1"},"reference-count":30,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2020,9,14]],"date-time":"2020-09-14T00:00:00Z","timestamp":1600041600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100009633","name":"Eunice Kennedy Shriver National Institute of Child Health and Human Development","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100009633","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Clinical Endocrinology"],"published-print":{"date-parts":[[2021,1]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Objectives<\/jats:title><jats:p>The postoperative period of Cushing disease (CD) is complicated by a phase of adrenal insufficiency (AI). Factors that influence the duration of AI and its prognostic significance for CD recurrence in children have not been extensively studied. We investigated whether clinical or biochemical factors contribute to the duration of AI, and the correlation of the recovery process with the risk for recurrence.<\/jats:p><\/jats:sec><jats:sec><jats:title>Design<\/jats:title><jats:p>Patients with paediatric\u2010onset CD who were followed up for at least 3\u00a0months after transsphenoidal surgery (TSS) (n\u00a0=\u00a0130) were included in the study. Multivariable Cox proportional hazards analysis was used to assess the association of biochemical and clinical factors with the duration of AI.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Overall, 102 patients recovered adrenal function during their follow\u2010up. Median time to recovery was 12.7\u00a0months [95% confidence intervals (CI): 12.2\u201013.4]. On multivariable analysis, clinical (age, gender, disease duration, puberty stage, BMI <jats:italic>z<\/jats:italic>\u2010score, tumour size, invasion of the cavernous sinus and year of surgery) and biochemical (midnight cortisol and morning ACTH) factors did not correlate with the time to recovery, except for increase in recovery time noted with increase in urinary free cortisol (UFC) [hazard ratio (HR): 0.94; 95% CI: 0.89\u20100.99]. Among patients who eventually recovered adrenal function, the risk for CD recurrence was associated with the time to recovery (HR: 0.86; 95% CI: 0.75\u20100.99).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Recovery of adrenal function in patients with CD after TSS may not be associated with most clinical and biochemical factors in the preoperative period except for total cortisol excretion. Earlier recovery is associated with higher risk for recurrence, which has implications for the patients\u2019 follow\u2010up and counselling.<\/jats:p><\/jats:sec>","DOI":"10.1111\/cen.14300","type":"journal-article","created":{"date-parts":[[2020,7,29]],"date-time":"2020-07-29T08:56:41Z","timestamp":1596013001000},"page":"40-47","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["Recovery of hypothalamic\u2010pituitary\u2010adrenal axis in paediatric Cushing disease"],"prefix":"10.1111","volume":"94","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2882-4584","authenticated-orcid":false,"given":"Christina","family":"Tatsi","sequence":"first","affiliation":[{"name":"Section on Endocrinology and Genetics <i>Eunice Kennedy Shriver<\/i> National Institute of Child Health and Human Development (NICHD) National Institutes of Health Bethesda MD USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Megan","family":"Neely","sequence":"additional","affiliation":[{"name":"Department of Biostatistics &amp; Bioinformatics Duke University School of Medicine Durham NC USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chelsi","family":"Flippo","sequence":"additional","affiliation":[{"name":"Section on Endocrinology and Genetics <i>Eunice Kennedy Shriver<\/i> National Institute of Child Health and Human Development (NICHD) National Institutes of Health Bethesda MD USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maria\u2010Eleni","family":"Bompou","sequence":"additional","affiliation":[{"name":"Section on Endocrinology and Genetics <i>Eunice Kennedy Shriver<\/i> National Institute of Child Health and Human Development (NICHD) National Institutes of Health Bethesda MD USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Meg","family":"Keil","sequence":"additional","affiliation":[{"name":"Section on Endocrinology and Genetics <i>Eunice Kennedy Shriver<\/i> National Institute of Child Health and Human Development (NICHD) National Institutes of Health Bethesda MD USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Constantine A.","family":"Stratakis","sequence":"additional","affiliation":[{"name":"Section on Endocrinology and Genetics <i>Eunice Kennedy Shriver<\/i> National Institute of Child Health and Human Development (NICHD) National Institutes of Health Bethesda MD USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2020,9,14]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ecl.2018.02.008"},{"issue":"6","key":"e_1_2_8_3_1","first-page":"1085","article-title":"Time to recovery of the hypothalamic\u2010pituitary\u2010adrenal axis after curative resection of adrenal tumors in patients with Cushing's syndrome","volume":"108","author":"Doherty GM","year":"1990","journal-title":"Surgery"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2015-1818"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1210\/jc.77.1.173"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1159\/000496846"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1111\/cen.13803"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2014-1401"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2265.2004.02111.x"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12020-016-1007-5"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2011-2325"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2008-0125"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ando.2018.03.010"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2014-3632"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ecl.2005.01.003"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.npp.1300856"},{"key":"e_1_2_8_17_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1749-6632.2002.tb04318.x"},{"key":"e_1_2_8_18_1","doi-asserted-by":"publisher","DOI":"10.1038\/npp.2015.215"},{"key":"e_1_2_8_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jad.2007.02.017"},{"key":"e_1_2_8_20_1","doi-asserted-by":"publisher","DOI":"10.1159\/000216192"},{"key":"e_1_2_8_21_1","unstructured":"TatsiC ZhangW PankratzN et al.Gene variants affecting cortisol secretion and function may regulate recovery time in Cushing disease. 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