{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T15:45:32Z","timestamp":1790696732833,"version":"4.1.0"},"reference-count":98,"publisher":"Oxford University Press (OUP)","issue":"4","content-domain":{"domain":["eje.bioscientifica.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2018,4]]},"abstract":"\n Background<\/jats:title>\n \n Recently discovered mutations of\n NR3C1<\/jats:italic>\n gene, encoding for the GR, in patients with glucocorticoid resistance and bilateral adrenal incidentalomas prompted us to investigate whether GR mutations might be associated with adrenal hyperplasia.\n <\/jats:p>\n <\/jats:sec>\n \n Objective<\/jats:title>\n The multicenter French Clinical Research Program (Muta-GR) was set up to determine the prevalence of GR mutations and polymorphisms in patients harboring bilateral adrenal incidentalomas associated with hypertension and\/or biological hypercortisolism without clinical Cushing\u2019s signs.<\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n \n One hundred patients were included in whom\n NR3C1<\/jats:italic>\n sequencing revealed five original heterozygous GR mutations that impaired GR signaling\n in vitro<\/jats:italic>\n . Mutated patients presented with mild glucocorticoid resistance defined as elevated urinary free cortisol (1.7\u2009\u00b1\u20090.7 vs 0.9\u2009\u00b1\u20090.8 upper limit of normal range,\n P<\/jats:italic>\n \u2009=\u20090.006), incomplete 1\u2009mg dexamethasone suppression test without suppressed 8-AM adrenocorticotrophin levels (30.9\u2009\u00b1\u200931.2 vs 16.2\u2009\u00b1\u200917.5\u2009pg\/mL) compared to the non-mutated patients. Potassium and aldosterone levels were lower in mutated patients (3.6\u2009\u00b1\u20090.2 vs 4.1\u2009\u00b1\u20090.5\u2009mmol\/L,\n P<\/jats:italic>\n \u2009=\u20090.01, and 17.3\u2009\u00b1\u20099.9 vs 98.6\u2009\u00b1\u2009115.4\u2009pg\/mL,\n P<\/jats:italic>\n \u2009=\u20090.0011, respectively) without elevated renin levels, consistent with pseudohypermineralocorticism.\n Ex vivo<\/jats:italic>\n characterization of mutated patients\u2019 fibroblasts demonstrated GR haploinsufficiency as revealed by below-normal glucocorticoid induction of\n FKBP5<\/jats:italic>\n gene expression. There was no association between GR polymorphisms and adrenal hyperplasia in this cohort, except an over-representation of\n BclI<\/jats:italic>\n polymorphism.\n <\/jats:p>\n <\/jats:sec>\n \n Conclusion<\/jats:title>\n \n The 5% prevalence of heterozygous\n NR3C1<\/jats:italic>\n mutations discovered in our series is higher than initially thought and encourages GR mutation screening in patients with adrenal incidentalomas to unambiguously differentiate from Cushing\u2019s states and to optimize personalized follow-up.\n <\/jats:p>\n <\/jats:sec>","DOI":"10.1530\/eje-17-1071","type":"journal-article","created":{"date-parts":[[2018,2,14]],"date-time":"2018-02-14T20:45:17Z","timestamp":1518641117000},"page":"411-423","update-policy":"https:\/\/doi.org\/10.1530\/crossmarkpolicy-1","source":"Crossref","is-referenced-by-count":47,"title":["Significant prevalence of NR3C1 mutations in incidentally discovered bilateral adrenal hyperplasia: results of the French MUTA-GR Study"],"prefix":"10.1093","volume":"178","author":[{"given":"G\u00e9raldine","family":"Vitellius","sequence":"first","affiliation":[{"name":"1INSERM UMR_S U1185, Fac Med Paris Sud, Universit\u00e9 Paris Sud, Universit\u00e9 Paris-Saclay, Le Kremlin Bic\u00eatre, France"},{"name":"2Service d\u2019Endocrinologie-Diab\u00e8te-Nutrition, H\u00f4pital Robert Debr\u00e9, CHU Reims, Reims, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S\u00e9verine","family":"Trabado","sequence":"additional","affiliation":[{"name":"1INSERM UMR_S U1185, Fac Med Paris Sud, Universit\u00e9 Paris Sud, Universit\u00e9 Paris-Saclay, Le Kremlin Bic\u00eatre, France"},{"name":"3Service de G\u00e9n\u00e9tique Mol\u00e9culaire, Pharmacog\u00e9n\u00e9tique et Hormonologie, H\u00f4pitaux Universitaires Paris Sud, AH-HP, CHU Bic\u00eatre, Le Kremlin Bic\u00eatre, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christine","family":"Hoeffel","sequence":"additional","affiliation":[{"name":"4Service de Radiologie, H\u00f4pital Robert Debr\u00e9, CRESTIC, CHU Reims-URCA, Reims, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J\u00e9r\u00f4me","family":"Bouligand","sequence":"additional","affiliation":[{"name":"1INSERM UMR_S U1185, Fac Med Paris Sud, Universit\u00e9 Paris Sud, Universit\u00e9 Paris-Saclay, Le Kremlin Bic\u00eatre, France"},{"name":"3Service de G\u00e9n\u00e9tique Mol\u00e9culaire, Pharmacog\u00e9n\u00e9tique et Hormonologie, H\u00f4pitaux Universitaires Paris Sud, AH-HP, CHU Bic\u00eatre, Le Kremlin Bic\u00eatre, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antoine","family":"Bennet","sequence":"additional","affiliation":[{"name":"5Service d\u2019Endocrinologie, Maladies M\u00e9taboliques et Nutrition, CHU Toulouse, Toulouse, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Frederic","family":"Castinetti","sequence":"additional","affiliation":[{"name":"6Service d\u2019Endocrinologie, CHU de la Timone, Marseille, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"B\u00e9n\u00e9dicte","family":"Decoudier","sequence":"additional","affiliation":[{"name":"2Service d\u2019Endocrinologie-Diab\u00e8te-Nutrition, H\u00f4pital Robert Debr\u00e9, CHU Reims, Reims, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anne","family":"Guiochon-Mantel","sequence":"additional","affiliation":[{"name":"1INSERM UMR_S U1185, Fac Med Paris Sud, Universit\u00e9 Paris Sud, Universit\u00e9 Paris-Saclay, Le Kremlin Bic\u00eatre, France"},{"name":"3Service de G\u00e9n\u00e9tique Mol\u00e9culaire, Pharmacog\u00e9n\u00e9tique et Hormonologie, H\u00f4pitaux Universitaires Paris Sud, AH-HP, CHU Bic\u00eatre, Le Kremlin Bic\u00eatre, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marc","family":"Lombes","sequence":"additional","affiliation":[{"name":"1INSERM UMR_S U1185, Fac Med Paris Sud, Universit\u00e9 Paris Sud, Universit\u00e9 Paris-Saclay, Le Kremlin Bic\u00eatre, France"},{"name":"7Service d\u2019Endocrinologie et des Maladies de la Reproduction, H\u00f4pitaux Universitaires Paris Sud, AH-HP, CHU Bic\u00eatre, Le Kremlin Bic\u00eatre, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brigitte","family":"Delemer","sequence":"additional","affiliation":[{"name":"2Service d\u2019Endocrinologie-Diab\u00e8te-Nutrition, H\u00f4pital Robert Debr\u00e9, CHU Reims, Reims, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"_","family":"_","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"_","family":"_","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"F","family":"Amiot-Chapoutot","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"D","family":"Ancelle","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"F","family":"Bertoin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"T","family":"Brue","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"P","family":"Caron","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"F","family":"Borson-Chazot","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S","family":"Christin-Maitre","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"O","family":"Chabre","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"R","family":"Dessailloud","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"B","family":"Estour","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"H","family":"Grulet","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"F","family":"Illouz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"N","family":"Jeandidier","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"V","family":"Kerlan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M","family":"Klein","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A","family":"Penfornis","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"P","family":"Pierre","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A","family":"Tabarin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"P","family":"Touraine","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M 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