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Noteworthy, pituitary hormonal deficiencies kept on evolving during adulthood in 49 of patients.\n                      <jats:italic>Growth Hormone<\/jats:italic>\n                      deficiency (GHD) affected 85.8% of patients and was often the first diagnosed deficiency.\n                      <jats:italic>AdrenoCorticoTropic<\/jats:italic>\n                      Hormone deficiency rarely preceded GHD, but usually followed it by over 10\u00a0years. Pituitary\n                      <jats:italic>Magnetic Resonance Imaging<\/jats:italic>\n                      (MRI) abnormalities were common (79.7%), with 39.4% pituitary stalk interruption syndrome (PSIS). The most frequently associated extrapituitary malformations were ophthalmological abnormalities (16.1%). Prevalence of identified mutations was 7.3% of index cases (84\/1143) and 29.5% in familial cases (n\u00a0=\u00a0146). Genetic analysis in 449 patients without extrapituitary phenotype revealed 36\n                      <jats:italic>PROP1<\/jats:italic>\n                      , 2\n                      <jats:italic>POU1F1<\/jats:italic>\n                      and 17\n                      <jats:italic>TBX19<\/jats:italic>\n                      mutations.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>\n                      This large international cohort highlights atypical phenotypic presentation of constitutional hypopituitarism, such as post pubertal presentation or adult progression of hormonal deficiencies. These results justify long\u2010term follow\u2010up, and the need for systematic evaluation of associated abnormalities. Genetic defects were rarely identified, mainly\n                      <jats:italic>PROP1<\/jats:italic>\n                      mutations in pure endocrine phenotypes.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/cen.14355","type":"journal-article","created":{"date-parts":[[2020,10,24]],"date-time":"2020-10-24T04:08:35Z","timestamp":1603512515000},"page":"277-289","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":47,"title":["Clinical lessons learned in constitutional hypopituitarism from two decades of experience in a large international cohort"],"prefix":"10.1111","volume":"94","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8273-2106","authenticated-orcid":false,"given":"Nicolas","family":"Jullien","sequence":"first","affiliation":[{"name":"Aix\u2010Marseille Univ CNRS INP, Inst Neurophysiopathol Marseille 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