{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,5]],"date-time":"2025-11-05T11:07:05Z","timestamp":1762340825050},"reference-count":50,"publisher":"Oxford University Press (OUP)","issue":"5","content-domain":{"domain":["eje.bioscientifica.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2015,11]]},"abstract":"<jats:sec><jats:title>Context<\/jats:title><jats:p>Patients with hypopituitarism have increased morbidity and mortality. There is ongoing debate about the optimum glucocorticoid (GC) replacement therapy.<\/jats:p><\/jats:sec><jats:sec><jats:title>Objective<\/jats:title><jats:p>To assess the effect of GC replacement in hypopituitarism on corticosteroid metabolism and its impact on body composition.<\/jats:p><\/jats:sec><jats:sec><jats:title>Design and patients<\/jats:title><jats:p>We assessed the urinary corticosteroid metabolite profile (using gas chromatography\/mass spectrometry) and body composition (clinical parameters and full body DXA) of 53 patients (19 female, median age 46 years) with hypopituitarism (33 ACTH-deficient\/20 ACTH-replete) (study A). The corticosteroid metabolite profile of ten patients with ACTH deficiency was then assessed prospectively in a cross over study using three hydrocortisone (HC) dosing regimens (20\/10\u200amg, 10\/10\u200amg and 10\/5\u200amg) (study B) each for 6 weeks. 11 beta-hydroxysteroid dehydrogenase 1 (11\u03b2-HSD1) activity was assessed by urinary THF+5\u03b1-THF\/THE.<\/jats:p><\/jats:sec><jats:sec><jats:title>Setting<\/jats:title><jats:p>Endocrine Centres within University Teaching Hospitals in the UK and Ireland.<\/jats:p><\/jats:sec><jats:sec><jats:title>Main outcome measures<\/jats:title><jats:p>Urinary corticosteroid metabolite profile and body composition assessment.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>In study A, when patients were divided into three groups \u2013 patients not receiving HC and patients receiving HC\u226420\u200amg\/day or HC&gt;20\u200amg\/day \u2013 patients in the group receiving the highest daily dose of HC had significantly higher waist-to-hip ratio (WHR) than the ACTH replete group. They also had significantly elevated THF+5\u03b1-THF\/THE (<jats:italic>P<\/jats:italic>=0.0002) and total cortisol metabolites (<jats:italic>P<\/jats:italic>=0.015). In study B, patients on the highest HC dose had significantly elevated total cortisol metabolites and all patients on HC had elevated THF+5\u03b1-THF\/THE ratios when compared to controls.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>In ACTH-deficient patients daily HC doses of &gt;20\u200amg\/day have increased WHR, THF+5\u03b1-THF\/THE ratios and total cortisol metabolites. GC metabolism and induction of 11\u03b2-HSD1 may play a pivitol role in the development of the metabolically adverse hypopituitary phenotype.<\/jats:p><\/jats:sec>","DOI":"10.1530\/eje-15-0490","type":"journal-article","created":{"date-parts":[[2015,8,12]],"date-time":"2015-08-12T01:01:22Z","timestamp":1439341282000},"page":"583-593","update-policy":"http:\/\/dx.doi.org\/10.1530\/crossmarkpolicy-1","source":"Crossref","is-referenced-by-count":16,"title":["The modulation of corticosteroid metabolism by hydrocortisone therapy in patients with hypopituitarism increases tissue glucocorticoid exposure"],"prefix":"10.1093","volume":"173","author":[{"given":"Mark","family":"Sherlock","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lucy Ann","family":"Behan","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mark J","family":"Hannon","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Aurora Aragon","family":"Alonso","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Christopher J","family":"Thompson","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Robert D","family":"Murray","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nicola","family":"Crabtree","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Beverly A","family":"Hughes","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wiebke","family":"Arlt","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Amar","family":"Agha","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Andrew A","family":"Toogood","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Paul M","family":"Stewart","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","reference":[{"key":"2015092818232211000_173.5.583.1","doi-asserted-by":"publisher","DOI":"10.1210\/er.2009-0033"},{"key":"2015092818232211000_173.5.583.2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2265.2007.02947.x"},{"key":"2015092818232211000_173.5.583.3","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2265.1997.d01-1749.x"},{"key":"2015092818232211000_173.5.583.4","doi-asserted-by":"publisher","DOI":"10.1016\/0140-6736(90)91812-O"},{"key":"2015092818232211000_173.5.583.5","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(00)04006-X"},{"key":"2015092818232211000_173.5.583.6","doi-asserted-by":"crossref","unstructured":"Beshyah SA Freemantle C Thomas E Rutherford O Page B Murphy M Johnston DG . 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