{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,7,30]],"date-time":"2025-07-30T13:53:35Z","timestamp":1753883615260,"version":"3.41.2"},"reference-count":10,"publisher":"The Endocrine Society","issue":"2","license":[{"start":{"date-parts":[[2025,1,23]],"date-time":"2025-01-23T00:00:00Z","timestamp":1737590400000},"content-version":"vor","delay-in-days":3,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025,1,20]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Glucocorticoid resistance syndrome (GRS) is caused by inactivating pathogenic variants in the glucocorticoid receptor gene NR3C1. Reduced glucocorticoid receptor signaling leads to decreased tissue sensitivity to cortisol and resultant biochemical hypercortisolism without the classic clinical features of Cushing syndrome. Patients variably present with signs and symptoms of mineralocorticoid and androgen excess from ACTH overstimulation of the adrenal cortex. Neuropsychiatric symptoms, such as anxiety, depression, anorexia, and insomnia, have also been reported and may be related to CRH excess. Due to the broad clinical spectrum and genetic heterogeneity of the disorder, it remains a diagnostic and treatment challenge. In this report, we describe 2 cases of GRS that highlight the genetic diversity of the condition. Both patients had prominent neuropsychiatric symptoms. While 1 patient had no identifiable variant in the glucocorticoid receptor gene, the other was found to have a novel NR3C1 variant. Low-dose dexamethasone treatment led to clinical improvement in the patient with negative genetic testing, and the second patient continues to be monitored.<\/jats:p>","DOI":"10.1210\/jcemcr\/luae243","type":"journal-article","created":{"date-parts":[[2025,1,23]],"date-time":"2025-01-23T15:22:23Z","timestamp":1737645743000},"source":"Crossref","is-referenced-by-count":0,"title":["Glucocorticoid Resistance Syndrome in 2 Patients With Diverse Genotype"],"prefix":"10.1210","volume":"3","author":[{"ORCID":"https:\/\/orcid.org\/0009-0006-8002-189X","authenticated-orcid":false,"given":"Tess","family":"Battiola","sequence":"first","affiliation":[{"name":"University of Utah Health, Division of Endocrinology , Salt Lake City, UT 84108 ,","place":["USA"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"David","family":"Viskochil","sequence":"additional","affiliation":[{"name":"University of Utah Health, Division of Medical Genetics , Salt Lake City , UT 84113","place":["USA"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kaci","family":"Wolken","sequence":"additional","affiliation":[{"name":"Haywood Regional Medical Center, Division of Internal Medicine , Clyde, NC 28721 ,","place":["USA"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-1726-8191","authenticated-orcid":false,"given":"Marie","family":"Couldwell","sequence":"additional","affiliation":[{"name":"University of Utah Health, Division of Endocrinology , Salt Lake City, UT 84108 ,","place":["USA"]}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"80","published-online":{"date-parts":[[2025,1,23]]},"reference":[{"issue":"5","key":"2025020513045310000_luae243-B1","doi-asserted-by":"crossref","first-page":"1563","DOI":"10.1210\/jc.2008-0040","article-title":"Generalized glucocorticoid resistance: clinical aspects, molecular mechanisms, and implications of a rare genetic disorder","volume":"93","author":"Charmandari","year":"2008","journal-title":"J Clin Endocrinol Metab"},{"issue":"2","key":"2025020513045310000_luae243-B2","doi-asserted-by":"crossref","first-page":"R15","DOI":"10.1530\/EJE-19-0811","article-title":"GENETICS IN ENDOCRINOLOGY: glucocorticoid resistance syndrome","volume":"182","author":"Vitellius","year":"2020","journal-title":"Eur J Endocrinol"},{"issue":"11","key":"2025020513045310000_luae243-B3","doi-asserted-by":"crossref","first-page":"1139","DOI":"10.1507\/endocrj.EJ18-0135","article-title":"Glucocorticoid resistance syndrome caused by a novel NR3C1 point mutation","volume":"65","author":"Al Argan","year":"2018","journal-title":"Endocr J"},{"issue":"1","key":"2025020513045310000_luae243-B4","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1186\/s40842-018-0072-5","article-title":"Cushing's syndrome with no clinical stigmata \u2013 a variant of glucocorticoid resistance syndrome","volume":"4","author":"Gossain","year":"2018","journal-title":"Clin Diabetes Endocrinol"},{"issue":"1","key":"2025020513045310000_luae243-B5","doi-asserted-by":"publisher","first-page":"luad153","DOI":"10.1210\/jcemcr\/luad153","article-title":"The glucocorticoid resistance syndrome. Two cases of a novel pathogenic variant in the glucocorticoid receptor gene","volume":"2","author":"Mauri","year":"2024","journal-title":"JCEM Case Rep"},{"issue":"11","key":"2025020513045310000_luae243-B6","doi-asserted-by":"crossref","first-page":"1113","DOI":"10.7326\/0003-4819-119-11-199312010-00009","article-title":"Syndromes of glucocorticoid resistance","volume":"119","author":"Chrousos","year":"1993","journal-title":"Ann Intern Med"},{"issue":"1","key":"2025020513045310000_luae243-B7","doi-asserted-by":"crossref","first-page":"31","DOI":"10.31887\/DCNS.2002.4.1\/jreul","article-title":"On the role of corticotropin-releasing hormone receptors in anxiety and depression","volume":"4","author":"Reul","year":"2002","journal-title":"Dialogues Clin Neurosci"},{"key":"2025020513045310000_luae243-B8","doi-asserted-by":"crossref","first-page":"117","DOI":"10.1016\/S0083-6729(04)69005-4","article-title":"CRH, stress, and major depression: a psychobiological interplay","volume":"69","author":"Claes","year":"2004","journal-title":"Vitam Horm"},{"issue":"1","key":"2025020513045310000_luae243-B9","doi-asserted-by":"crossref","first-page":"50","DOI":"10.1080\/07853890310017044","article-title":"Corticotropin-releasing hormone (CRH) in psychiatry: from stress to psychopathology","volume":"36","author":"Claes","year":"2004","journal-title":"Ann Med"},{"issue":"20","key":"2025020513045310000_luae243-B10","doi-asserted-by":"crossref","first-page":"11595","DOI":"10.1073\/pnas.96.20.11595","article-title":"Altered anxiety and weight gain in corticotropin-releasing hormone-binding protein-deficient mice","volume":"96","author":"Karolyi","year":"1999","journal-title":"Proc Natl Acad Sci U S A"}],"container-title":["JCEM Case Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/jcemcr\/article-pdf\/3\/2\/luae243\/61585586\/luae243.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/jcemcr\/article-pdf\/3\/2\/luae243\/61585586\/luae243.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,2,5]],"date-time":"2025-02-05T13:08:35Z","timestamp":1738760915000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/jcemcr\/article\/doi\/10.1210\/jcemcr\/luae243\/7976570"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,1,20]]},"references-count":10,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2025,1,20]]}},"URL":"https:\/\/doi.org\/10.1210\/jcemcr\/luae243","relation":{},"ISSN":["2755-1520"],"issn-type":[{"type":"electronic","value":"2755-1520"}],"subject":[],"published-other":{"date-parts":[[2025,2]]},"published":{"date-parts":[[2025,1,20]]},"article-number":"luae243"}}