Clinical lessons learned in constitutional hypopituitarism from two decades of experience in a large international cohort - l'unam - université nantes angers le mans Accéder directement au contenu
Article Dans Une Revue Clinical Endocrinology Année : 2021

Clinical lessons learned in constitutional hypopituitarism from two decades of experience in a large international cohort

Nicolas Jullien
Emeline Marquant
Agnès Linglart
Patrice Rodien

Résumé

Context The international GENHYPOPIT network collects phenotypical data and screens genetic causes of non‐acquired hypopituitarism. Aims To describe main phenotype patterns and their evolution through life. Design Patients were screened according to their phenotype for coding sequence variations in 8 genes: HESX1, LHX3, LHX4, PROP1, POU1F1, TBX19, OTX2 and PROKR2. Results Among 1213 patients (1143 index cases), the age of diagnosis of hypopituitarism was congenital (24%), in childhood (28%), at puberty (32%), in adulthood (7.2%) or not available (8.8%). Noteworthy, pituitary hormonal deficiencies kept on evolving during adulthood in 49 of patients. Growth Hormone deficiency (GHD) affected 85.8% of patients and was often the first diagnosed deficiency. AdrenoCorticoTropic Hormone deficiency rarely preceded GHD, but usually followed it by over 10 years. Pituitary Magnetic Resonance Imaging (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 = 146). Genetic analysis in 449 patients without extrapituitary phenotype revealed 36 PROP1, 2 POU1F1 and 17 TBX19 mutations. Conclusion 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‐term follow‐up, and the need for systematic evaluation of associated abnormalities. Genetic defects were rarely identified, mainly PROP1 mutations in pure endocrine phenotypes.
Fichier principal
Vignette du fichier
Jullien 2020.pdf (553.02 Ko) Télécharger le fichier
Origine : Fichiers produits par l'(les) auteur(s)

Dates et versions

hal-03225618 , version 1 (12-05-2021)

Identifiants

Citer

Nicolas Jullien, Alexandru Saveanu, Julia Vergier, Emeline Marquant, Marie Helene Quentien, et al.. Clinical lessons learned in constitutional hypopituitarism from two decades of experience in a large international cohort. Clinical Endocrinology, 2021, 94 (2), pp.277-289. ⟨10.1111/cen.14355⟩. ⟨hal-03225618⟩
80 Consultations
188 Téléchargements

Altmetric

Partager

Gmail Facebook X LinkedIn More