{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T02:47:51Z","timestamp":1787021271761,"version":"build-2736575974"},"reference-count":31,"publisher":"The Endocrine Society","issue":"1","license":[{"start":{"date-parts":[[2021,8,14]],"date-time":"2021-08-14T00:00:00Z","timestamp":1628899200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000062","name":"National Institute of Diabetes and Digestive and Kidney Diseases","doi-asserted-by":"publisher","award":["K08DK109116"],"award-info":[{"award-number":["K08DK109116"]}],"id":[{"id":"10.13039\/100000062","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2022,1,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Context<\/jats:title>\n                    <jats:p>Testicular adrenal rest tumors (TART) are a common complication in males with classic 21-hydroxylase deficiency (21OHD). TART are likely to contribute to the androgen excess in 21OHD patients, but a direct quantification of steroidogenesis from these tumors has not been yet done.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>We aimed to define the production of 11-oxygenated 19-carbon (11oxC19) steroids by TART.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Using liquid chromatography-tandem mass spectrometry, steroids were measured in left (n\u2005=\u20057) and right (n\u2005=\u20054) spermatic vein and simultaneously drawn peripheral blood (n\u2005=\u20057) samples from 7 men with 21OHD and TART. For comparison, we also measured the peripheral steroid concentrations in 5 adrenalectomized patients and 12 age- and BMI-matched controls. Additionally, steroids were quantified in TART cell\u2013 and adrenal cell\u2013conditioned medium, with and without adrenocorticotropic hormone (ACTH) stimulation.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Compared with peripheral blood from 21OHD patients with TART, the spermatic vein samples displayed the highest gradient for 11\u03b2-hydroxytestosterone (11OHT; 96-fold) of the 11oxC19 steroids, followed by 11-ketotestosterone (47-fold) and 11\u03b2-hydroxyandrostenedione (11OHA4; 29-fold), suggesting production of these steroids in TART. TART cells produced higher levels of testosterone and lower levels of A4 and 11OHA4 after ACTH stimulation compared with adrenal cells, indicating ACTH-induced production of testosterone in TART.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>In patients with 21OHD, TART produce 11oxC19 steroids, but in different proportions than the adrenals. The very high ratio of 11OHT in spermatic vs peripheral vein blood suggests the 11-hydroxylation of testosterone by TART, and the in vitro results indicate that this metabolism is ACTH-sensitive.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1210\/clinem\/dgab598","type":"journal-article","created":{"date-parts":[[2021,8,14]],"date-time":"2021-08-14T08:40:57Z","timestamp":1628930457000},"page":"e272-e280","source":"Crossref","is-referenced-by-count":22,"title":["Production of 11-Oxygenated Androgens by Testicular Adrenal Rest Tumors"],"prefix":"10.1210","volume":"107","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2139-9076","authenticated-orcid":false,"given":"Mariska A M","family":"Schr\u00f6der","sequence":"first","affiliation":[{"name":"Department of Pediatrics, Radboud Amalia Children\u2019s Hospital, Radboud University Medical Center, 6500 HB Nijmegen, The Netherlands"},{"name":"Department of Laboratory Medicine, Radboud Institute for Molecular Life Sciences (RIMLS), Radboud University Medical Center, 6500 HB Nijmegen, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adina F","family":"Turcu","sequence":"additional","affiliation":[{"name":"Division of Metabolism, Endocrinology and Diabetes, University of Michigan, Ann Arbor, MI 48109, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patrick","family":"O\u2019Day","sequence":"additional","affiliation":[{"name":"Division of Metabolism, Endocrinology and Diabetes, University of Michigan, Ann Arbor, MI 48109, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antonius E","family":"van Herwaarden","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine, Radboud Institute for Molecular Life Sciences (RIMLS), Radboud University Medical Center, 6500 HB Nijmegen, The 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":"Radiotherapy & OncoImmunology Laboratory, Department of Radiation Oncology, Radboud Institute for Molecular Life Sciences (RIMLS), Radboud University Medical Center, 6500 HB Nijmegen, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6815-6181","authenticated-orcid":false,"given":"Richard J","family":"Auchus","sequence":"additional","affiliation":[{"name":"Division of Metabolism, Endocrinology and Diabetes, University of Michigan, Ann Arbor, MI 48109, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fred C G J","family":"Sweep","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine, Radboud Institute for Molecular Life Sciences (RIMLS), Radboud University Medical Center, 6500 HB Nijmegen, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0181-0403","authenticated-orcid":false,"given":"Hedi L","family":"Claahsen-van der Grinten","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Radboud Amalia Children\u2019s Hospital, Radboud University Medical Center, 6500 HB Nijmegen, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"80","published-online":{"date-parts":[[2021,8,14]]},"reference":[{"issue":"6","key":"2021121823132122500_CIT0001","doi-asserted-by":"crossref","first-page":"2179","DOI":"10.1210\/jc.2005-1890","article-title":"Serum 21-Deoxycortisol, 17-Hydroxyprogesterone, and 11-deoxycortisol in classic congenital adrenal hyperplasia: clinical and hormonal correlations and identification of patients with 11beta-hydroxylase deficiency among a large group with alleged 21-hydroxylase 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