{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,8]],"date-time":"2026-07-08T22:19:53Z","timestamp":1783549193534,"version":"3.55.0"},"reference-count":52,"publisher":"Oxford University Press (OUP)","issue":"3","license":[{"start":{"date-parts":[[2024,8,22]],"date-time":"2024-08-22T00:00:00Z","timestamp":1724284800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/100010269","name":"Wellcome Trust","doi-asserted-by":"publisher","award":["WT209492\/Z\/17\/Z"],"award-info":[{"award-number":["WT209492\/Z\/17\/Z"]}],"id":[{"id":"10.13039\/100010269","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100007155","name":"Medical Research Council","doi-asserted-by":"publisher","award":["MC_UP_1605\/15"],"award-info":[{"award-number":["MC_UP_1605\/15"]}],"id":[{"id":"10.13039\/501100007155","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","award":["314061271"],"award-info":[{"award-number":["314061271"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]},{"name":"AMEND ACC Research Fund 2022"},{"name":"HRA Pharma Rare Disease"},{"name":"British Society of Paediatric Endocrinology and Diabetes, Barts Charity","award":["MGU0458"],"award-info":[{"award-number":["MGU0458"]}]},{"name":"Academy of Medical Sciences Fellowship Grant","award":["G0802796"],"award-info":[{"award-number":["G0802796"]}]},{"name":"Collaborative Awards in Science and Engineering","award":["MR\/R015686\/2442100"],"award-info":[{"award-number":["MR\/R015686\/2442100"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2024,8,30]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Background<\/jats:title>\n                  <jats:p>Primary bilateral macronodular adrenal hyperplasia (PBMAH) is a rare cause of Cushing's syndrome. Individuals with PBMAH and glucose-dependent insulinotropic polypeptide (GIP)-dependent Cushing's syndrome due to ectopic expression of the GIP receptor (GIPR) typically harbor inactivating KDM1A sequence variants. Primary unilateral macronodular adrenal hyperplasia (PUMAH) with concomitant glucocorticoid and androgen excess has never been encountered or studied.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>We investigated a woman with a large, heterogeneous adrenal mass and severe adrenocorticotropic hormone-independent glucocorticoid and androgen excess, a biochemical presentation typically suggestive of adrenocortical carcinoma. The patient presented during pregnancy (22nd week of gestation) and reported an 18-month history of oligomenorrhea, hirsutism, and weight gain. We undertook an exploratory study with detailed histopathological and genetic analysis of the resected adrenal mass and leukocyte DNA collected from the patient and her parents.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>Histopathology revealed benign macronodular adrenal hyperplasia. Imaging showed a persistently normal contralateral adrenal gland. Whole-exome sequencing of 4 representative nodules detected KDM1A germline variants, benign NM_001009999.3:c.136G &amp;gt; A:p.G46S, and likely pathogenic NM_001009999.3:exon6:c.865_866del:p.R289Dfs*7. Copy number variation analysis demonstrated an additional somatic loss of the KDM1A wild-type allele on chromosome 1p36.12 in all nodules. RNA sequencing of a representative nodule showed low\/absent KDM1A expression and increased GIPR expression compared with 52 unilateral sporadic adenomas and 4 normal adrenal glands. Luteinizing hormone\/chorionic gonadotropin receptor expression was normal. Sanger sequencing confirmed heterozygous KDM1A variants in both parents (father: p.R289Dfs*7 and mother: p.G46S) who showed no clinical features suggestive of glucocorticoid or androgen excess.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>We investigated the first PUMAH associated with severe Cushing's syndrome and concomitant androgen excess, suggesting pathogenic mechanisms involving KDM1A.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/ejendo\/lvae106","type":"journal-article","created":{"date-parts":[[2024,8,22]],"date-time":"2024-08-22T23:15:42Z","timestamp":1724368542000},"page":"334-344","source":"Crossref","is-referenced-by-count":5,"title":["Primary unilateral macronodular adrenal hyperplasia with concomitant glucocorticoid and androgen excess and <i>KDM1A<\/i> inactivation"],"prefix":"10.1093","volume":"191","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2735-6053","authenticated-orcid":false,"given":"Yasir S","family":"Elhassan","sequence":"first","affiliation":[{"name":"Institute of Metabolism and Systems Research, University of Birmingham , Birmingham ,","place":["United Kingdom"]},{"name":"Centre for Endocrinology, Diabetes and Metabolism, University Hospitals Birmingham NHS Foundation Trust, Birmingham Health Partners , Birmingham ,","place":["United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Silke","family":"Appenzeller","sequence":"additional","affiliation":[{"name":"Comprehensive Cancer Center Mainfranken, University of W\u00fcrzburg , W\u00fcrzburg ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6315-4176","authenticated-orcid":false,"given":"Laura-Sophie","family":"Landwehr","sequence":"additional","affiliation":[{"name":"Division of Endocrinology and Diabetes, Department of Internal Medicine I, University Hospital, University of W\u00fcrzburg , W\u00fcrzburg ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juliane","family":"Lippert","sequence":"additional","affiliation":[{"name":"Division of Endocrinology and Diabetes, Department of Internal Medicine I, University Hospital, University of W\u00fcrzburg , W\u00fcrzburg ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7984-3171","authenticated-orcid":false,"given":"Dillon","family":"Popat","sequence":"additional","affiliation":[{"name":"Faculty of Medicine and Dentistry, Centre for Endocrinology, William Harvey Research Institute, Queen Mary University of London , London ,","place":["United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lorna C","family":"Gilligan","sequence":"additional","affiliation":[{"name":"Institute of Metabolism and Systems Research, University of Birmingham , Birmingham ,","place":["United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lida","family":"Abdi","sequence":"additional","affiliation":[{"name":"MRC Laboratory of Medical Sciences , London ,","place":["United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Edwina","family":"Goh","sequence":"additional","affiliation":[{"name":"Birmingham Women's Hospital , Birmingham ,","place":["United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Salvador","family":"Diaz-Cano","sequence":"additional","affiliation":[{"name":"Department of Pathology, University Hospitals Birmingham NHS Foundation Trust , Birmingham ,","place":["United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefan","family":"Kircher","sequence":"additional","affiliation":[{"name":"Department of Pathology, University of W\u00fcrzburg , W\u00fcrzburg ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Susanne","family":"Gramlich","sequence":"additional","affiliation":[{"name":"Department of Pathology, University of W\u00fcrzburg , W\u00fcrzburg ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert P","family":"Sutcliffe","sequence":"additional","affiliation":[{"name":"The Liver Unit, Queen Elizabeth Hospital Birmingham, University Hospitals Birmingham NHS Foundation Trust , Birmingham ,","place":["United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shakila","family":"Thangaratinam","sequence":"additional","affiliation":[{"name":"Institute of Metabolism and Systems Research, University of Birmingham , Birmingham ,","place":["United Kingdom"]},{"name":"Birmingham Women's Hospital , Birmingham ,","place":["United Kingdom"]},{"name":"NIHR Birmingham Biomedical Research Centre, University Hospitals Birmingham NHS Foundation Trust and University of Birmingham , Birmingham ,","place":["United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Li F","family":"Chan","sequence":"additional","affiliation":[{"name":"Faculty of Medicine and Dentistry, Centre for Endocrinology, William Harvey Research Institute, Queen Mary University of London , London ,","place":["United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6170-6398","authenticated-orcid":false,"given":"Martin","family":"Fassnacht","sequence":"additional","affiliation":[{"name":"Comprehensive Cancer Center Mainfranken, University of W\u00fcrzburg , W\u00fcrzburg ,","place":["Germany"]},{"name":"Division of Endocrinology and Diabetes, Department of Internal Medicine I, University Hospital, University of W\u00fcrzburg , W\u00fcrzburg ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5106-9719","authenticated-orcid":false,"given":"Wiebke","family":"Arlt","sequence":"additional","affiliation":[{"name":"Institute of Metabolism and Systems Research, University of Birmingham , Birmingham ,","place":["United Kingdom"]},{"name":"MRC Laboratory of Medical Sciences , London ,","place":["United Kingdom"]},{"name":"Faculty of Medicine, Institute of Clinical Sciences, Imperial College London , London ,","place":["United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5020-2071","authenticated-orcid":false,"given":"Cristina L","family":"Ronchi","sequence":"additional","affiliation":[{"name":"Institute of Metabolism and Systems Research, University of Birmingham , Birmingham ,","place":["United 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