{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,19]],"date-time":"2026-05-19T05:14:45Z","timestamp":1779167685476,"version":"3.51.4"},"reference-count":36,"publisher":"Georg Thieme Verlag KG","issue":"07","funder":[{"name":"the Regional Health authorities of Western Norway, the Research Council of Norway and K.G. Jebsen of Autoimmune Diseases."}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Horm Metab Res"],"published-print":{"date-parts":[[2023,7]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Pulsatile endogenous cortisol secretion is critical for physiological\n                    glucocorticoid gene signaling. Conventional glucocorticoid replacement therapy\n                    does not mimic endogenous cortisol pulsing in primary adrenal insufficiency. In\n                    an open-labeled, two-week, nonrandomized cross-over study of five patients with\n                    adrenal insufficiency (Addison\u2019s disease in two, bilateral adrenalectomy\n                    in one, and congenital adrenal hyperplasia in two patients) we compared\n                    pulsatile and continuous cortisol pump treatment and conventional oral\n                    glucocorticoid therapy with respect to 24-h serum corticosteroid levels and\n                    plasma adrenocorticotropic hormone (ACTH). Pulsed pump restored ultradian\n                    rhythmicity as demonstrated by five peaks of serum (all patients) and\n                    subcutaneous tissue cortisol (four patients). Morning subcutaneous cortisol and\n                    cortisone were higher in continuous and pulsed pump treatment than in oral\n                    therapy despite nearly similar serum cortisol levels in all treatment arms. ACTH\n                    was within the physiological range during pulsed pump treatment in all patients\n                    except for slightly elevated levels in the morning hours\n                    04:00\u201308:00\u2009h. During oral therapy, ACTH was very high in\n                    patients with Addison\u2019s disease and suppressed in patients with\n                    congenital adrenal hyperplasia. In conclusions, mimicking endogenous cortisol\n                    rhythmicity by ultradian subcutaneous infusion of cortisol is feasible. It was\n                    superior to both continuous pump and oral therapy in maintaining normal ACTH\n                    levels throughout the 24-h cycle. Our results demonstrate a low free cortisol\n                    bioavailability on thrice daily oral replacement therapy compared to both types\n                    of subcutaneous infusion.<\/jats:p>","DOI":"10.1055\/a-2092-5228","type":"journal-article","created":{"date-parts":[[2023,5,12]],"date-time":"2023-05-12T23:48:58Z","timestamp":1683935338000},"page":"471-478","source":"Crossref","is-referenced-by-count":4,"title":["Pulsatile Subcutaneous Hydrocortisone Replacement in Primary Adrenal\n                    Insufficiency"],"prefix":"10.1055","volume":"55","clinical-trial-number":[{"clinical-trial-number":"nct02096510","registry":"10.18810\/clinical-trials-gov"}],"author":[{"given":"Katerina","family":"Simunkova","sequence":"additional","affiliation":[{"name":"Department of Clinical Science, Faculty of Medicine and Dentistry,\n                    University of Bergen, Bergen, Norway"},{"name":"Departments of Endocrinology, Haukeland University Hospital, Bergen,\n                    Norway"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kristian","family":"L\u00f8v\u00e5s","sequence":"additional","affiliation":[{"name":"Department of Clinical Science, Faculty of Medicine and Dentistry,\n                    University of Bergen, Bergen, Norway"},{"name":"Departments of Endocrinology, Haukeland University Hospital, Bergen,\n                    Norway"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Paal","family":"Methlie","sequence":"additional","affiliation":[{"name":"Department of Clinical Science, Faculty of Medicine and Dentistry,\n                    University of Bergen, Bergen, Norway"},{"name":"Departments of Endocrinology, Haukeland University Hospital, Bergen,\n                    Norway"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nevena","family":"Jovanovic","sequence":"additional","affiliation":[{"name":"Departments of Endocrinology, Haukeland University Hospital, Bergen,\n                    Norway"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ersilia","family":"Bifulco","sequence":"additional","affiliation":[{"name":"Department of Clinical Science, Faculty of Medicine and Dentistry,\n                    University of Bergen, Bergen, Norway"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ingeborg","family":"Bronstad","sequence":"additional","affiliation":[{"name":"Department of Clinical Science, Faculty of Medicine and Dentistry,\n                    University of Bergen, Bergen, Norway"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"S. L.","family":"Lightman","sequence":"additional","affiliation":[{"name":"The Henry Wellcome Laboratories for Integrative Neuroscience and\n                    Endocrinology, University of Bristol, Bristol, United Kingdom of Great Britain\n                    and Northern Ireland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Eystein Sverre","family":"Husebye","sequence":"additional","affiliation":[{"name":"Department of Clinical Science, Faculty of Medicine and Dentistry,\n                    University of Bergen, Bergen, Norway"},{"name":"Departments of Endocrinology, Haukeland University Hospital, Bergen,\n                    Norway"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marianne","family":"Oksnes","sequence":"additional","affiliation":[{"name":"Department of Clinical Science, Faculty of Medicine and Dentistry,\n                    University of Bergen, Bergen, Norway"},{"name":"Departments of Endocrinology, Haukeland University Hospital, Bergen,\n                    Norway"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"194","published-online":{"date-parts":[[2023,7,10]]},"reference":[{"key":"ref1","doi-asserted-by":"crossref","first-page":"3339","DOI":"10.1016\/j.lfs.2003.05.007","article-title":"Reproducibility of the circadian rhythms of serum cortisol and melatonin in\n                    healthy subjects: a study of three different 24-h cycles over six weeks","volume":"73","author":"B Selmaoui","year":"2003","journal-title":"Life Sci"},{"key":"ref2","doi-asserted-by":"crossref","first-page":"255","DOI":"10.1016\/j.ejphar.2007.11.073","article-title":"The significance of glucocorticoid pulsatility","volume":"583","author":"L S Lightman","year":"2008","journal-title":"Eur J Pharmacol"},{"key":"ref3","first-page":"E6","article-title":"Amplitude modulation of a burstlike mode of cortisol secretion subserves the\n                    circadian glucocorticoid rhythm","volume":"257","author":"J D 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Meta"},{"key":"ref13","doi-asserted-by":"crossref","first-page":"R231","DOI":"10.1530\/EJE-17-0154","article-title":"Management of endocrine disease: risk of overtreatment in patients with adrenal\n                    insufficiency: current and emerging aspects","volume":"177","author":"G Mazziotti","year":"2017","journal-title":"Eur J Endocrinol"},{"key":"ref14","doi-asserted-by":"crossref","first-page":"1665","DOI":"10.1210\/jc.2013-4253","article-title":"Continuous subcutaneous hydrocortisone infusion versus oral hydrocortisone\n                    replacement for treatment of Addison\u2019s disease: a randomized clinical\n                    trial","volume":"99","author":"M \u00d8ksnes","year":"2014","journal-title":"J Clin Endocrinol Metab"},{"key":"ref15","doi-asserted-by":"crossref","first-page":"E4091","DOI":"10.1073\/pnas.1714239115","article-title":"Ultradian rhythmicity of plasma cortisol is necessary for normal emotional and\n                    cognitive responses in 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formulation","volume":"97","author":"G Johannsson","year":"2012","journal-title":"J Clin Endocrinol Metab"},{"key":"ref35","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1111\/j.1365-2265.2006.02544.x","article-title":"Circadian hydrocortisone infusions in patients with adrenal insufficiency and\n                    congenital adrenal hyperplasia","volume":"65","author":"Z Merza","year":"2006","journal-title":"Clin Endocrinol (Oxf)"},{"key":"ref36","doi-asserted-by":"crossref","first-page":"561","DOI":"10.1515\/jpem.2011.226","article-title":"Continuous subcutaneous hydrocortisone infusion (CSHI) in a young adolescent\n                    with congenital adrenal hyperplasia (CAH)","volume":"24","author":"G Tuli","year":"2011","journal-title":"J Pediatr Endocrinol Metab"}],"container-title":["Hormone and Metabolic Research"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/www.thieme-connect.de\/products\/ejournals\/pdf\/10.1055\/a-2092-5228.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,7,26]],"date-time":"2023-07-26T17:31:25Z","timestamp":1690392685000},"score":1,"resource":{"primary":{"URL":"http:\/\/www.thieme-connect.de\/DOI\/DOI?10.1055\/a-2092-5228"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,5,12]]},"references-count":36,"journal-issue":{"issue":"07","published-online":{"date-parts":[[2023,7,10]]},"published-print":{"date-parts":[[2023,7]]}},"URL":"https:\/\/doi.org\/10.1055\/a-2092-5228","archive":["Portico","CLOCKSS"],"relation":{},"ISSN":["0018-5043","1439-4286"],"issn-type":[{"value":"0018-5043","type":"print"},{"value":"1439-4286","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2023,5,12]]},"published":{"date-parts":[[2023,5,12]]}}}