{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,1]],"date-time":"2026-05-01T14:20:43Z","timestamp":1777645243018,"version":"3.51.4"},"reference-count":24,"publisher":"The Endocrine Society","issue":"5","license":[{"start":{"date-parts":[[2026,4,21]],"date-time":"2026-04-21T00:00:00Z","timestamp":1776729600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,4,21]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Generalized glucocorticoid (GC) resistance (Chrousos syndrome) results from impaired GC receptor signaling due to variants in the NR3C1 gene. Severe neonatal presentations are extremely rare. We report an 8-week-old male infant born at 31-week gestation, with progressive respiratory failure, refractory hypotension, hypokalemic alkalosis, anasarca, jaundice, and multiorgan dysfunction. Laboratory evaluation demonstrated persistently elevated serum cortisol [&amp;gt;60\u2005\u00b5g\/dL (SI: &amp;gt;1655\u2005nmol\/L) (reference range 2.5-9.1\u2005\u00b5g\/dL, SI: 69.0-251.0\u2005nmol\/L)], adrenocorticotropic hormone [&amp;gt;2400\u2005pg\/mL (SI: &amp;gt;528\u2005pmol\/L) (reference range 7.2-63.3\u2005pg\/mL, SI: 1.6-13.9\u2005pmol\/L)], aldosterone [2036.0\u2005ng\/dL (SI: 56\u2005nmol\/L) (reference range 7.0-99.0\u2005ng\/dL, SI: 0.2-2.7\u2005nmol\/L)], and androgens despite treatment with escalating doses of dexamethasone (up to 12\u2005mg, &amp;gt; 2000\u2005mg\/m2\/day of hydrocortisone-equivalency). Whole-genome sequencing identified 2 NR3C1 variants: a maternally inherited variant of uncertain significance (c.2181+5 G&amp;gt;C) and a de novo likely pathogenic \u223c7.9\u2005kb deletion encompassing exon 8. In silico analyses suggested both variants could disrupt the GC receptor ligand-binding domain, potentially resulting in complete loss of GC receptor function. Autopsy demonstrated adrenomegaly with marked proliferation of zona fasciculata, cholestasis with bile duct paucity, and chronic neonatal lung disease. This case represents a rare and fatal manifestation of complete generalized GC resistance. It highlights the broad physiological role of GC in neonatal homeostasis.<\/jats:p>","DOI":"10.1210\/jcemcr\/luag079","type":"journal-article","created":{"date-parts":[[2026,3,4]],"date-time":"2026-03-04T12:46:23Z","timestamp":1772628383000},"source":"Crossref","is-referenced-by-count":0,"title":["Complete glucocorticoid resistance: a lethal disorder in the neonatal period"],"prefix":"10.1210","volume":"4","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1212-9082","authenticated-orcid":false,"given":"Natalie","family":"Segev","sequence":"first","affiliation":[{"name":"Department of Pediatrics, University of Cincinnati College of Medicine , Cincinnati, OH 45219 ,","place":["USA"]},{"name":"Division of Diabetes and Endocrinology, Cincinnati Children's Hospital Medical Center , Cincinnati, OH 45229 ,","place":["USA"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7298-4959","authenticated-orcid":false,"given":"Sarah","family":"Swauger","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, University of Cincinnati College of Medicine , Cincinnati, OH 45219 ,","place":["USA"]},{"name":"Division of Diabetes and Endocrinology, Cincinnati Children's Hospital Medical Center , Cincinnati, OH 45229 ,","place":["USA"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"K Nicole","family":"Weaver","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, University of Cincinnati College of Medicine , Cincinnati, OH 45219 ,","place":["USA"]},{"name":"Division of Human Genetics, Cincinnati Children's Hospital Medical Center , Cincinnati, OH 45229 ,","place":["USA"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shipra","family":"Jain","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, University of Cincinnati College of Medicine , Cincinnati, OH 45219 ,","place":["USA"]},{"name":"Division of Neonatology and Pulmonary Biology, Cincinnati Children's Hospital Medical Center , Cincinnati, OH 45229 ,","place":["USA"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kalyani R","family":"Patel","sequence":"additional","affiliation":[{"name":"Division of Pathology, Cincinnati Children's Hospital Medical Center , Cincinnati, OH 45229 ,","place":["USA"]},{"name":"Department of Pathology and Laboratory Medicine, University of Cincinnati College of Medicine , Cincinnati, OH 45219 ,","place":["USA"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Philippe","family":"Backeljauw","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, University of Cincinnati College of Medicine , Cincinnati, OH 45219 ,","place":["USA"]},{"name":"Division of Diabetes and Endocrinology, Cincinnati Children's Hospital Medical Center , Cincinnati, OH 45229 ,","place":["USA"]}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"80","published-online":{"date-parts":[[2026,4,21]]},"reference":[{"key":"2026042902313301400_luag079-B1","first-page":"85","article-title":"Glucocorticoid resistance","volume":"111","author":"Nicolaides","year":"2019","journal-title":"Exp Suppl"},{"issue":"6","key":"2026042902313301400_luag079-B2","doi-asserted-by":"crossref","first-page":"1261","DOI":"10.1172\/JCI110565","article-title":"Primary cortisol resistance in man. 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