title: Screening for genetic causes of growth hormone hypersecretion.
abstract: Growth hormone (GH) secreting pituitary tumors may be caused by genetic abnormalities in a variety of genes including AIP, MEN1, CDKN1B, and PRKAR1A. These can lead to GH secreting pituitary adenomas as an isolated occurrence (e.g. as aggressive sporadic adenomas or in familial isolated pituitary adenomas (FIPA)) or as part of syndromic conditions such as MEN1 or Carney complex. These tumors have more aggressive features than sporadic acromegaly, including a younger age at disease onset and larger tumor size, and they can be challenging to manage. In addition to mutations or deletions, copy number variation at the GPR101 locus may also lead to mixed GH and prolactin secreting pituitary adenomas in the setting of X-linked acrogigantism (X-LAG syndrome). In X-LAG syndrome and in McCune Albright syndrome, mosaicism for GPR101 duplications and activating GNAS1 mutations, respectively, contribute to the genetic pathogenesis. As only 5% of pituitary adenomas have a known cause, efficient deployment of genetic testing requires detailed knowledge of clinical characteristics and potential associated syndromic features in the patient and their family.
authors.affiliation: Department of Endocrinology, Centre Hospitalier Universitaire de Liège, University of Liège, Domaine Universitaire du Sart-Tilman, 4000 Liège, Belgium.
authors.forename: Liliya
authors.initials: L
authors.lastname: Rostomyan
authors.affiliation: Department of Endocrinology, Centre Hospitalier Universitaire de Liège, University of Liège, Domaine Universitaire du Sart-Tilman, 4000 Liège, Belgium. Electronic address: albert.beckers@chu.ulg.ac.be.
authors.forename: Albert
authors.initials: A
authors.lastname: Beckers
mesh_terms: D000236:Adenoma / Q000235:genetics*; D056733:Carney Complex / Q000235:genetics; D002864:Chromogranins / Q000235:genetics; D054756:Cyclic AMP-Dependent Protein Kinase RIalpha Subunit / Q000235:genetics; D050760:Cyclin-Dependent Kinase Inhibitor p27 / Q000235:genetics; D005359:Fibrous Dysplasia, Polyostotic / Q000235:genetics; D019205:GTP-Binding Protein alpha Subunits, Gs / Q000235:genetics; D040181:Genetic Diseases, X-Linked / Q000235:genetics*; D005820:Genetic Testing; D049912:Growth Hormone-Secreting Pituitary Adenoma / Q000235:genetics*; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics; D009377:Multiple Endocrine Neoplasia / Q000235:genetics; D011518:Proto-Oncogene Proteins / Q000235:genetics; D043562:Receptors, G-Protein-Coupled / Q000235:genetics; D013385:Succinate Dehydrogenase / Q000235:genetics
chemical_list: C436291:CDKN1B protein, human; D002864:Chromogranins; D054756:Cyclic AMP-Dependent Protein Kinase RIalpha Subunit; C000594175:GPR101 protein, human; D047908:Intracellular Signaling Peptides and Proteins; C105373:MEN1 protein, human; C517834:PRKAR1A protein, human; D011518:Proto-Oncogene Proteins; D043562:Receptors, G-Protein-Coupled; C103265:aryl hydrocarbon receptor-interacting protein; D050760:Cyclin-Dependent Kinase Inhibitor p27; D013385:Succinate Dehydrogenase; C406732:GNAS protein, human; D019205:GTP-Binding Protein alpha Subunits, Gs
keywords: Acromegaly; Aryl hydrocarbon receptor interacting protein gene; Carney complex; Familial isolated pituitary adenoma (FIPA); GPR101; Gigantism; McCune-Albright syndrome; Multiple endocrine neoplasia; Somatotropinoma; X-linked acrogigantism (X-LAG) syndrome