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Hydrocortisone (ie, cortisol) is the recommended glucocorticoid for treatment of CAH. However, the other endogenous glucocorticoid in humans, corticosterone, is actively transported out of metabolic tissues such as adipose tissue and muscle, so we hypothesized that corticosterone could control adrenal androgens while causing fewer metabolic adverse effects than hydrocortisone.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>Thirteen patients (8 female, 5 male) with CAH due to 21-hydroxylase deficiency completed a randomized placebo-controlled crossover study comparing 5\u2005h intravenous infusions of either hydrocortisone, corticosterone or placebo. 6-6[2H]2-glucose and 1,1,2,3,3-[2H]5-glycerol were infused to measure glucose and glycerol kinetics, and blood samples were collected throughout. Subcutaneous abdominal adipose tissue biopsies were obtained at the end of each infusion.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>During the infusion, corticosterone and hydrocortisone similarly reduced ACTH, 17\u03b1-hydroxyprogesterone, androstenedione, and testosterone (in females only) compared with placebo. Despite achieving circulating corticosterone concentrations \u223c2.5-fold higher than hydrocortisone, by T + 300\u2005min hydrocortisone but not corticosterone increased glucose and insulin concentrations and reduced 6-6-[2H]2-glucose clearance compared with placebo. Hydrocortisone increased mRNA levels of the glucocorticoid regulated transcript PER1 in adipose to a greater extent than corticosterone.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>Corticosterone acutely controls biochemical markers of androgen excess similarly to hydrocortisone but without inducing markers of glucocorticoid \u201ctoxicity\u201d in CAH. These data demonstrate proof of concept that corticosterone may be a safer glucocorticoid replacement than current medications, although further research is required to assess the longer-term effects of corticosterone replacement.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/ejendo\/lvae144","type":"journal-article","created":{"date-parts":[[2024,11,15]],"date-time":"2024-11-15T19:32:07Z","timestamp":1731699127000},"page":"535-544","source":"Crossref","is-referenced-by-count":4,"title":["Proof of concept for a superior therapeutic index of corticosterone compared with hydrocortisone in patients with congenital adrenal hyperplasia"],"prefix":"10.1093","volume":"191","author":[{"given":"Catriona J","family":"Kyle","sequence":"first","affiliation":[{"name":"University\/BHF Centre for Cardiovascular Science, Queen's Medical Research Institute, University of Edinburgh , EH16 4TJ ,","place":["United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luke 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