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They are secreted by the adrenal cortex under the control of the hypothalamic\u2010pituitary\u2010adrenal (<jats:styled-content style=\"fixed-case\">HPA<\/jats:styled-content>) axis. Glucocorticoids are essential for the normal function of most organ systems and, in both, excess and deficiency can lead to significant adverse consequences. Adrenal insufficiency (<jats:styled-content style=\"fixed-case\">AI<\/jats:styled-content>) is a rare, life\u2010threatening disorder characterized by insufficient production of corticosteroid hormones. Primary <jats:styled-content style=\"fixed-case\">AI<\/jats:styled-content> is defined by the inability of the adrenal cortex to produce sufficient amounts of glucocorticoids and\/or mineralocorticoids despite normal or increased adrenocorticotropin hormone (<jats:styled-content style=\"fixed-case\">ACTH<\/jats:styled-content>). Secondary <jats:styled-content style=\"fixed-case\">AI<\/jats:styled-content> is adrenal hypofunction due to insufficient amount of <jats:styled-content style=\"fixed-case\">ACTH<\/jats:styled-content> produced by the pituitary gland. Conventional treatment of both primary and secondary adrenal insufficiencies involves lifelong glucocorticoid replacement therapy. The role of cortisol deficiency and the impact of hydrocortisone replacement on morbidity and mortality in this patient group are under increasing scrutiny. Established glucocorticoid replacement regimens do not completely mirror endogenous hormonal production, and their monitoring to ensure optimum therapy is hampered by the lack of reliable biomarkers of hormone sufficiency. A further confounding issue is the tissue\u2010specific regulation of glucocorticoid through the two isozymes of 11\u03b2\u2010hydroxysteroid dehydrogenase (11\u03b2\u2010<jats:styled-content style=\"fixed-case\">HSD<\/jats:styled-content>) with research focusing on the role of this prereceptor regulation in the development of adverse metabolic features in patients. This review defines the factors influencing glucocorticoid action in patients with adrenal insufficiency receiving glucocorticoid therapy.<\/jats:p>","DOI":"10.1111\/cen.13837","type":"journal-article","created":{"date-parts":[[2018,8,18]],"date-time":"2018-08-18T06:43:58Z","timestamp":1534574638000},"page":"3-14","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":30,"title":["Factors impacting on the action of glucocorticoids in patients receiving glucocorticoid therapy"],"prefix":"10.1111","volume":"90","author":[{"given":"Rosemary","family":"Dineen","sequence":"first","affiliation":[{"name":"Academic Department of Endocrinology Beaumont Hospital and the Royal College of Surgeons in Ireland  Dublin Ireland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul M.","family":"Stewart","sequence":"additional","affiliation":[{"name":"Department of Endocrinology University of Leeds  Leeds 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