{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T23:57:04Z","timestamp":1790035024732,"version":"4.0.1"},"reference-count":18,"publisher":"The Endocrine Society","issue":"11","funder":[{"name":"Faculty of Medicine Grant, Diponegoro University, Semarang, Indonesia","award":["Funding: This work was partially funded by Faculty of Medicine Grant, Diponegoro University, Semarang, Indonesia (PNBP FK.T.A. 2016 Number 3817\/UN7.3.4\/PG\/2016)."],"award-info":[{"award-number":["Funding: This work was partially funded by Faculty of Medicine Grant, Diponegoro University, Semarang, Indonesia (PNBP FK.T.A. 2016 Number 3817\/UN7.3.4\/PG\/2016)."]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2019,11,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Context and Objective<\/jats:title>\n                  <jats:p>We describe the clinical features and biochemical characteristics of a unique population of severely affected untreated patients with congenital adrenal hyperplasia (CAH) from an Indonesian population with proven cortisol deficiency but without clinical signs of cortisol deficiency. We evaluated the in vitro glucocorticoid activity of all relevant adrenal steroid precursors occurring in patients with CAH.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Design<\/jats:title>\n                  <jats:p>Cross-sectional cohort study and translational research.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Intervention\/Main Outcome Measures<\/jats:title>\n                  <jats:p>Adrenal steroid precursor concentrations before and 60 minutes after ACTH administration to 24 untreated patients with CAH (3 to 46 years) with proven cortisol deficiency (&lt;500 nmol\/L post-ACTH) measured by liquid chromatography\u2013tandem mass spectrometry were compared with six control patients (Mann-Whitney U test). Glucocorticoid receptor (GR) activation was determined by dual-luciferase assays in human embryonic kidney cells transfected with the GR and exposed to increasing amounts of adrenal steroid precursors for 24 hours.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>Blood concentrations of the steroid precursors 11-deoxycortisol (457 nmol\/L, P = 0.003), 11-deoxycorticosterone (55 nmol\/L, P = 0.003), 17-hydroxyprogesterone (610 nmol\/L, P &lt; 0.001), progesterone (29 nmol\/L, P &lt; 0.001), and 21-deoxycortisol (73 nmol\/L) were strongly elevated compared with control subjects. The GR was activated with comparable potency to cortisol by corticosterone and 21-deoxycortisol or with 4 to 100 times lower potency by 11-hydroxyprogesterone, 11-deoxycortisol, aldosterone, 11-deoxycorticosterone, progesterone, and 17-hydroxyprogesterone.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>We identified strongly elevated adrenal steroid precursor concentrations in blood from untreated patients with CAH and demonstrated glucocorticoid activity of these adrenal precursors in vitro, suggesting a possible role of these precursors in the clinical phenotype of these patients. Further studies are necessary to evaluate the role of these precursors in more detail.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1210\/jc.2019-00547","type":"journal-article","created":{"date-parts":[[2019,5,15]],"date-time":"2019-05-15T09:09:47Z","timestamp":1557911387000},"page":"5065-5072","source":"Crossref","is-referenced-by-count":43,"title":["Glucocorticoid Activity of Adrenal Steroid Precursors in Untreated Patients With Congenital Adrenal Hyperplasia"],"prefix":"10.1210","volume":"104","author":[{"given":"Manon","family":"Engels","sequence":"first","affiliation":[{"name":"Radboud University Medical Center, Radboud Institute for Molecular Life Sciences, Amalia Children's Hospital, Department of Pediatrics, Nijmegen, Netherlands"},{"name":"Radboud University Medical Center, Radboud Institute for Molecular Life Sciences, Department of Laboratory Medicine, Nijmegen, Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karijn J","family":"Pijnenburg-Kleizen","sequence":"additional","affiliation":[{"name":"Radboud University Medical Center, Radboud Institute for Molecular Life Sciences, Amalia Children's Hospital, Department of Pediatrics, Nijmegen, Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Agustini","family":"Utari","sequence":"additional","affiliation":[{"name":"Division of Human Genetics, Center for Biomedical Research (CEBIOR), Faculty of Medicine Diponegoro University, Tembalang Semarang, Indonesia"},{"name":"Division of Pediatric Endocrinology, department of Pediatrics, Faculty of Medicine Diponegoro University, Tembalang Semarang, Indonesia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sultana M H","family":"Faradz","sequence":"additional","affiliation":[{"name":"Division of Human Genetics, Center for Biomedical Research (CEBIOR), Faculty of Medicine Diponegoro University, Tembalang Semarang, Indonesia"},{"name":"Division of Pediatric Endocrinology, department of Pediatrics, Faculty of Medicine Diponegoro University, Tembalang Semarang, Indonesia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sandra","family":"Oude-Alink","sequence":"additional","affiliation":[{"name":"Radboud University Medical Center, Radboud Institute for Molecular Life Sciences, Department of Laboratory Medicine, Nijmegen, Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antonius E","family":"van Herwaarden","sequence":"additional","affiliation":[{"name":"Radboud University Medical Center, Radboud Institute for Molecular Life Sciences, Department of Laboratory Medicine, Nijmegen, Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1930-6638","authenticated-orcid":false,"given":"Paul N","family":"Span","sequence":"additional","affiliation":[{"name":"Radboud University Medical Center, Radboud Institute for Molecular Life Sciences, Department of 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