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However, discovery of cortisone in the 1940s not only improved the life expectancy of these patients but also had a dramatic effect on their overall quality of life. The diagnosis, easily confirmed by demonstrating inappropriately low cortisol secretion, is often delayed by months, and many patients present with acute adrenal crisis. Sudden withdrawal from chronic glucocorticoid therapy is the most common cause of AI. Currently, there remains a wide variation in the management of this condition across Europe. As primary AI is a relatively rare condition, most medical specialists will only manage a handful of these patients in their career. Despite many advances in recent years, there is currently no curative option, and modern cortisol replacement regimens fail to adequately mimic physiological cortisol rhythm. A number of new approaches including allograft of adrenocortical tissue and stem cell therapy are being tried but remain largely experimental.<\/jats:p>","DOI":"10.1136\/jclinpath-2021-207895","type":"journal-article","created":{"date-parts":[[2022,5,23]],"date-time":"2022-05-23T12:52:19Z","timestamp":1653310339000},"page":"435-442","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":47,"title":["Adrenal insufficiency"],"prefix":"10.1136","volume":"75","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9887-0025","authenticated-orcid":false,"given":"Rajeev","family":"Kumar","sequence":"first","affiliation":[{"name":"Diabetes and Endocrinology, Bedfordshire Hospitals NHS Foundation Trust, Bedford, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"W S","family":"Wassif","sequence":"additional","affiliation":[{"name":"Clinical Biochemistry, Bedfordshire Hospitals NHS Foundation Trust, Bedford, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"239","published-online":{"date-parts":[[2022,5,9]]},"reference":[{"key":"2025092504150517000_75.7.435.1","doi-asserted-by":"publisher","DOI":"10.1001\/jama.1977.03270430057020"},{"key":"2025092504150517000_75.7.435.2","doi-asserted-by":"crossref","DOI":"10.3389\/fnins.2016.00238","article-title":"Functional zonation of the adult mammalian adrenal cortex","volume":"10","author":"Vinson","year":"2016","journal-title":"Front Neurosci"},{"key":"2025092504150517000_75.7.435.3","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2265.2002.01466.x"},{"key":"2025092504150517000_75.7.435.4","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2006-0076"},{"key":"2025092504150517000_75.7.435.5","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(68)90948-3"},{"key":"2025092504150517000_75.7.435.6","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2265.2002.t01-1-01552.x"},{"key":"2025092504150517000_75.7.435.7","doi-asserted-by":"publisher","DOI":"10.1530\/EJE-13-0756"},{"key":"2025092504150517000_75.7.435.8","doi-asserted-by":"publisher","DOI":"10.1210\/jc.84.5.1762"},{"key":"2025092504150517000_75.7.435.9","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(03)13492-7"},{"key":"2025092504150517000_75.7.435.10","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2265.2001.01406.x"},{"key":"2025092504150517000_75.7.435.11","doi-asserted-by":"publisher","DOI":"10.1530\/EJE-15-0608"},{"key":"2025092504150517000_75.7.435.12","unstructured":"Addison T . 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