{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T16:12:22Z","timestamp":1790611942149,"version":"4.1.0"},"reference-count":25,"publisher":"Oxford University Press (OUP)","issue":"1","license":[{"start":{"date-parts":[[2025,6,13]],"date-time":"2025-06-13T00:00:00Z","timestamp":1749772800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"name":"\u201cFrance G\u00e9nomique\u201d consortium","award":["ANR-10-INBS-009"],"award-info":[{"award-number":["ANR-10-INBS-009"]}]},{"name":"European Union\u2019s Horizon Europe Research and Innovation Programme","award":["101080465"],"award-info":[{"award-number":["101080465"]}]},{"name":"National Center for Precision Diabetic Medicine"},{"DOI":"10.13039\/501100001665","name":"French National Agency for Research","doi-asserted-by":"publisher","award":["ANR-18-IBHU-0001"],"award-info":[{"award-number":["ANR-18-IBHU-0001"]}],"id":[{"id":"10.13039\/501100001665","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000780","name":"European Union","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100000780","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100014161","name":"Hauts-de-France Regional Council","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100014161","id-type":"DOI","asserted-by":"publisher"}]},{"name":"European Metropolis of Lille"},{"DOI":"10.13039\/501100000781","name":"European Research Council","doi-asserted-by":"publisher","award":["ERC OpiO \u2013 101043671"],"award-info":[{"award-number":["ERC OpiO \u2013 101043671"]}],"id":[{"id":"10.13039\/501100000781","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025,6,30]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Objective<\/jats:title>\n                  <jats:p>Biallelic variants in the pro-opiomelanocortin gene (POMC) can cause hypocortisolism, hypopigmentation, and early-onset obesity. Following the identification of 2 patients of combined pituitary hormone deficiency (CPHD), we investigated the prevalence of this association among carriers of rare pathogenic or likely pathogenic (P\/LP) POMC variants.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Design<\/jats:title>\n                  <jats:p>This study is a case report and systematic literature review.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>Genetic analysis was conducted in a family with 2 cousins with childhood-onset obesity and CPHD. We assessed CPHD in carriers for biallelic pathogenic POMC variants using data from the literature and Human Gene Mutation Database. Clinical and biological data were collected, including pituitary axis involvement, obesity onset age, and pituitary imaging results.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>The 2 cousins, compound heterozygous for POMC variants, developed CPHD following initial hypocortisolism, with subsequent hypothyroidism, growth hormone deficiency, and hypogonadism. Among 41 patients with biallelic POMC variants identified in the literature, 20 had rare homozygous\/compound heterozygous P\/LP POMC variants and detailed endocrine evaluations. Of these, 40% presented with CPHD, always associated with early-onset severe obesity and hypocortisolism. Growth hormone deficiency was the most frequent (75%), followed by thyrotropic and gonadotropic deficiencies (62.5%). No anomalies were revealed in pituitary imaging. Two patients recovered the gonadotropic axis after treatment with the MC4R agonist.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusion<\/jats:title>\n                  <jats:p>These findings underscore the potential for CPHD to occur in carriers of biallelic pathogenic POMC variants. Sequencing the full POMC, including coding and regulatory regions, is crucial in CPHD cases, alongside evaluating all pituitary axes in neonatal hypocortisolism. Beyond weight regulation, setmelanotide may modulate hypothalamic-pituitary function, with implications for fertility.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/ejendo\/lvaf127","type":"journal-article","created":{"date-parts":[[2025,6,13]],"date-time":"2025-06-13T20:58:59Z","timestamp":1749848339000},"page":"31-38","source":"Crossref","is-referenced-by-count":1,"title":["Biallelic pathogenic variants in <i>POMC<\/i> can cause combined pituitary hormonal deficiency associated with severe obesity"],"prefix":"10.1093","volume":"193","author":[{"given":"G\u00e9raldine","family":"Vitellius","sequence":"first","affiliation":[{"name":"Service Diab\u00e9tologie Endocrinologie Nutrition, CHU Robert Debr\u00e9 , Rue du General Koenig, Reims 51100 ,","place":["France"]},{"name":"Faculty of Sport Sciences, Performance, Health, Metrology, Society Laboratory , University of Reims, Reims 51100 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75013 ,","place":["France"]},{"name":"Reference Center for Rare Diseases (PRADORT, Prader-Willi Syndrome and Other Rare Forms of Obesity with Eating Behavior Disorders) , Paris 75013 ,","place":["France"]},{"name":"Sorbonne Universit\u00e9, Assistance Publique-H\u00f4pitaux de Paris Nutrition Department, Piti\u00e9-Salp\u00eatri\u00e8re Hospital , Paris 75013 ,","place":["France"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jean Michel","family":"Petit","sequence":"additional","affiliation":[{"name":"D\u00e9partement d\u2019Endocrinologie, Diab\u00e9tologie, et Maladies M\u00e9taboliques, H\u00f4pital Universitaire de Dijon , Dijon 21000 ,","place":["France"]},{"name":"INSERM LNC UMR1231 , Dijon 21000 ,","place":["France"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7399-1330","authenticated-orcid":false,"given":"Blandine","family":"Gatta Cherifi","sequence":"additional","affiliation":[{"name":"Endocrinology Department, Haut-L\u00e9v\u00eaque Hospital , Pessac 33607 ,","place":["France"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Souhila","family":"Amanzougarene","sequence":"additional","affiliation":[{"name":"Lille University Hospital, University of Lille , Lille 59000 ,","place":["France"]},{"name":"Inserm\/CNRS UMR 1283\/8199, Institut Pasteur de Lille, EGID , Lille 59045 ,","place":["France"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mehdi","family":"Derhourhi","sequence":"additional","affiliation":[{"name":"Lille University Hospital, University of Lille , Lille 59000 ,","place":["France"]},{"name":"Inserm\/CNRS UMR 1283\/8199, Institut Pasteur de Lille, EGID , Lille 59045 ,","place":["France"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexandru","family":"Saveanu","sequence":"additional","affiliation":[{"name":"Laboratory of Molecular Biology GEnOP\u00e9 France Centre de R\u00e9f\u00e9rence des Maladies Rares de 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