{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T04:13:16Z","timestamp":1790914396793,"version":"4.1.0"},"reference-count":55,"publisher":"The Endocrine Society","issue":"7","license":[{"start":{"date-parts":[[2022,3,31]],"date-time":"2022-03-31T00:00:00Z","timestamp":1648684800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"name":"Research Foundation-Flanders","award":["G091918N"],"award-info":[{"award-number":["G091918N"]}]},{"name":"Methusalem Program of the Flemish Government","award":["METH\/14\/06"],"award-info":[{"award-number":["METH\/14\/06"]}]},{"DOI":"10.13039\/501100000781","name":"European Research Council","doi-asserted-by":"publisher","award":["AdvG-2017-785809"],"award-info":[{"award-number":["AdvG-2017-785809"]}],"id":[{"id":"10.13039\/501100000781","id-type":"DOI","asserted-by":"publisher"}]},{"name":"European Union\u2019s Horizon 2020 research and innovation program"},{"DOI":"10.13039\/100008593","name":"European Respiratory Society","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100008593","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2022,6,16]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Critical illnesses are hallmarked by increased systemic cortisol availability, a vital part of the stress response. Acute stress may trigger a life-threatening adrenal crisis when a disease of the hypothalamic\u2013pituitary\u2013adrenal (HPA) axis is present and not adequately treated with stress doses of hydrocortisone. Stress doses of hydrocortisone are also used to reduce high vasopressor need in patients suffering from septic shock, in the absence of adrenal insufficiency. Research performed over the last 10 years focusing on the HPA axis during critical illness has led to the insight that neither of these conditions can be labeled \u201ccritical illness\u2013induced corticosteroid insufficiency\u201d or CIRCI. Instead, these data suggested using the term CIRCI for a condition that may develop in prolonged critically ill patients. Indeed, when patients remain dependent on vital organ support for weeks, they are at risk of acquiring central adrenal insufficiency. The sustained increase in systemic glucocorticoid availability, mainly brought about by suppressed circulating cortisol-binding proteins and suppressed hepatic\/renal cortisol metabolism, exerts negative feedback inhibition at the hypothalamus\/pituitary, while high levels of other glucocorticoid receptor ligands, such as bile acids, and drugs, such as opioids, may further suppress adrenocorticotropic hormone (ACTH) secretion. The adrenal cortex, depleted from ACTH-mediated trophic signaling for weeks, may become structurally and functionally impaired, resulting in insufficient cortisol production. Such a central HPA axis suppression may be maladaptive by contributing to lingering vasopressor need and encephalopathy, hence preventing recovery. Here, we review this concept of CIRCI and we advise on how to recognize and treat this poorly understood condition.<\/jats:p>","DOI":"10.1210\/clinem\/dgac201","type":"journal-article","created":{"date-parts":[[2022,3,31]],"date-time":"2022-03-31T16:20:46Z","timestamp":1648743646000},"page":"2057-2064","source":"Crossref","is-referenced-by-count":58,"title":["Critical Illness\u2013induced Corticosteroid Insufficiency: What It Is Not and What It Could Be"],"prefix":"10.1210","volume":"107","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8829-0855","authenticated-orcid":false,"given":"Arno","family":"T\u00e9blick","sequence":"first","affiliation":[{"name":"Clinical Division and Laboratory of Intensive Care Medicine, Department of Cellular and Molecular Medicine, KU Leuven University , B-3000 Leuven , Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2470-6393","authenticated-orcid":false,"given":"Jan","family":"Gunst","sequence":"additional","affiliation":[{"name":"Clinical Division and Laboratory of Intensive Care Medicine, Department of Cellular and Molecular Medicine, KU Leuven University , B-3000 Leuven , Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5320-1362","authenticated-orcid":false,"given":"Greet","family":"Van den Berghe","sequence":"additional","affiliation":[{"name":"Clinical Division and Laboratory of Intensive Care Medicine, Department of Cellular and Molecular Medicine, KU Leuven University , B-3000 Leuven , Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"80","published-online":{"date-parts":[[2022,3,31]]},"reference":[{"issue":"8","key":"2022061616041255000_CIT0001","first-page":"422","article-title":"Recherches experimentales sur la physiologie et la pathologie des capsules surrenales","volume":"43","author":"Brown-S\u00e9quard","year":"1856","journal-title":"C r hebd s\u00e9ances Acad sci."},{"issue":"5362","key":"2022061616041255000_CIT0002","doi-asserted-by":"crossref","first-page":"887","DOI":"10.1136\/bmj.2.5362.887","article-title":"Eighty-Six Cases of Addison\u2019s Disease","volume":"2","author":"Dunlop","year":"1963","journal-title":"Br Med J"},{"issue":"9","key":"2022061616041255000_CIT0003","doi-asserted-by":"crossref","first-page":"525","DOI":"10.1038\/s41574-019-0228-0","article-title":"The human stress response","volume":"15","author":"Russell","year":"2019","journal-title":"Nat Rev Endocrinol."},{"issue":"9","key":"2022061616041255000_CIT0004","doi-asserted-by":"crossref","first-page":"518","DOI":"10.1016\/j.tips.2013.07.003","article-title":"Glucocorticoid receptor signaling in health and disease","volume":"34","author":"Kadmiel","year":"2013","journal-title":"Trends Pharmacol Sci."},{"issue":"1","key":"2022061616041255000_CIT0005","doi-asserted-by":"crossref","first-page":"283","DOI":"10.1002\/cphy.c170022","article-title":"Adrenocortical stress response during the course of critical illness","volume":"8","author":"Peeters","year":"2017","journal-title":"Compr Physiol"},{"issue":"7","key":"2022061616041255000_CIT0006","doi-asserted-by":"crossref","first-page":"417","DOI":"10.1038\/s41574-019-0185-7","article-title":"Adrenal function and dysfunction in critically ill patients","volume":"15","author":"Teblick","year":"2019","journal-title":"Nat Rev Endocrinol."},{"issue":"1","key":"2022061616041255000_CIT0007","doi-asserted-by":"crossref","first-page":"281","DOI":"10.1210\/jc.2003-030440","article-title":"Association of 24-hour cortisol production rates, cortisol-binding globulin, and plasma-free cortisol levels with body composition, leptin levels, and aging in adult men and women","volume":"89","author":"Purnell","year":"2004","journal-title":"J Clin Endocrinol Metab."},{"issue":"3","key":"2022061616041255000_CIT0008","doi-asserted-by":"crossref","first-page":"367","DOI":"10.1111\/j.1365-2265.2004.02106.x","article-title":"Weight-related dosing, timing and monitoring hydrocortisone replacement therapy in patients with adrenal insufficiency","volume":"61","author":"Mah","year":"2004","journal-title":"Clin Endocrinol (Oxf)"},{"issue":"10274","key":"2022061616041255000_CIT0009","doi-asserted-by":"crossref","first-page":"613","DOI":"10.1016\/S0140-6736(21)00136-7","article-title":"Adrenal insufficiency","volume":"397","author":"Husebye","year":"2021","journal-title":"Lancet"},{"issue":"4","key":"2022061616041255000_CIT0010","doi-asserted-by":"crossref","first-page":"260","DOI":"10.1111\/j.1399-6576.1975.tb05182.x","article-title":"A rational approach to dosage and preparation of parenteral glucocorticoid substitution therapy during surgical procedures. 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