{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,26]],"date-time":"2026-09-26T10:53:00Z","timestamp":1790419980330,"version":"4.1.0"},"reference-count":144,"publisher":"The Endocrine Society","issue":"5","license":[{"start":{"date-parts":[[2024,5,2]],"date-time":"2024-05-02T00:00:00Z","timestamp":1714608000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"name":"Fonds d\u2019Investissement Pour la Recherche Scientifique"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2024,9,12]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Pituitary gigantism is a rare manifestation of chronic growth hormone (GH) excess that begins before closure of the growth plates. Nearly half of patients with pituitary gigantism have an identifiable genetic cause. X-linked acrogigantism (X-LAG; 10% of pituitary gigantism) typically begins during infancy and can lead to the tallest individuals described. In the 10 years since its discovery, about 40 patients have been identified. Patients with X-LAG usually develop mixed GH and prolactin macroadenomas with occasional hyperplasia that secrete copious amounts of GH, and frequently prolactin. Circulating GH-releasing hormone is also elevated in a proportion of patients. X-LAG is caused by constitutive or sporadic mosaic duplications at chromosome Xq26.3 that disrupt the normal chromatin architecture of a topologically associating domain (TAD) around the orphan G-protein\u2013coupled receptor, GPR101. This leads to the formation of a neo-TAD in which GPR101 overexpression is driven by ectopic enhancers (\u201cTADopathy\u201d). X-LAG has been seen in 3 families due to transmission of the duplication from affected mothers to sons. GPR101 is a constitutively active receptor with an unknown natural ligand that signals via multiple G proteins and protein kinases A and C to promote GH\/prolactin hypersecretion. Treatment of X-LAG is challenging due to the young patient population and resistance to somatostatin analogs; the GH receptor antagonist pegvisomant is often an effective option. GH, insulin-like growth factor 1, and prolactin hypersecretion and physical overgrowth can be controlled before definitive adult gigantism occurs, often at the cost of permanent hypopituitarism.<\/jats:p>","DOI":"10.1210\/endrev\/bnae014","type":"journal-article","created":{"date-parts":[[2024,4,29]],"date-time":"2024-04-29T19:53:24Z","timestamp":1714420404000},"page":"737-754","source":"Crossref","is-referenced-by-count":21,"title":["The Genetic Pathophysiology and Clinical Management of the TADopathy, X-Linked Acrogigantism"],"prefix":"10.1210","volume":"45","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6130-2975","authenticated-orcid":false,"given":"Adrian F","family":"Daly","sequence":"first","affiliation":[{"name":"Department of Endocrinology, Centre Hospitalier Universitaire (CHU) de Li\u00e8ge, University of Li\u00e8ge, Domaine Universitaire Sart Tilman , 4000 Li\u00e8ge , Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6351-1367","authenticated-orcid":false,"given":"Albert","family":"Beckers","sequence":"additional","affiliation":[{"name":"Department of Endocrinology, Centre Hospitalier Universitaire (CHU) de Li\u00e8ge, University of Li\u00e8ge, Domaine Universitaire Sart Tilman , 4000 Li\u00e8ge , Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"80","published-online":{"date-parts":[[2024,5,2]]},"reference":[{"issue":"3","key":"2024091719341162100_bnae014-B1","doi-asserted-by":"crossref","first-page":"347","DOI":"10.1016\/j.ecl.2020.04.002","article-title":"The epidemiology of pituitary adenomas","volume":"49","author":"Daly","year":"2020","journal-title":"Endocrinol Metab Clin North Am"},{"issue":"10","key":"2024091719341162100_bnae014-B2","doi-asserted-by":"crossref","first-page":"505","DOI":"10.1530\/ERC-17-0253","article-title":"Acromegaly at diagnosis in 3173 patients from the Li\u00e8ge Acromegaly Survey (LAS) database","volume":"24","author":"Petrossians","year":"2017","journal-title":"Endocr Relat Cancer"},{"issue":"1","key":"2024091719341162100_bnae014-B3","doi-asserted-by":"crossref","first-page":"20","DOI":"10.1038\/s41572-019-0071-6","article-title":"Acromegaly","volume":"5","author":"Colao","year":"2019","journal-title":"Nat Rev Dis Primers"},{"issue":"12","key":"2024091719341162100_bnae014-B4","doi-asserted-by":"crossref","first-page":"705","DOI":"10.1038\/s41574-018-0114-1","article-title":"The causes and consequences of pituitary gigantism","volume":"14","author":"Beckers","year":"2018","journal-title":"Nat Rev Endocrinol"},{"key":"2024091719341162100_bnae014-B5","volume-title":"\u00c9tudes Biologiques sur les G\u00e9ants","author":"Launois","year":"1904"},{"issue":"3","key":"2024091719341162100_bnae014-B6","doi-asserted-by":"crossref","first-page":"433","DOI":"10.1016\/j.ecl.2020.05.005","article-title":"Update on the genetics of pituitary tumors","volume":"49","author":"Barry","year":"2020","journal-title":"Endocrinol Metab Clin North Am"},{"issue":"6","key":"2024091719341162100_bnae014-B7","doi-asserted-by":"crossref","first-page":"R235","DOI":"10.1530\/EJE-19-0602","article-title":"Somatic and germline mutations in the pathogenesis of pituitary adenomas","volume":"181","author":"Vandeva","year":"2019","journal-title":"Eur J Endocrinol"},{"key":"2024091719341162100_bnae014-B8","doi-asserted-by":"crossref","first-page":"649","DOI":"10.1016\/B978-0-323-99899-4.00014-7","volume-title":"The Pituitary","author":"Daly","year":"2022"},{"issue":"3","key":"2024091719341162100_bnae014-B9","doi-asserted-by":"crossref","first-page":"e220291","DOI":"10.1530\/JOE-22-0291","article-title":"Pituitary tumours: molecular and genetic aspects","volume":"257","author":"De Sousa","year":"2023","journal-title":"J Endocrinol"},{"issue":"5","key":"2024091719341162100_bnae014-B10","doi-asserted-by":"crossref","first-page":"689","DOI":"10.1007\/s11102-022-01253-9","article-title":"Genetics of Cushing's disease: from the lab to clinical practice","volume":"25","author":"Theodoropoulou","year":"2022","journal-title":"Pituitary"},{"issue":"2","key":"2024091719341162100_bnae014-B11","doi-asserted-by":"crossref","first-page":"243","DOI":"10.1353\/lm.2010.0016","article-title":"The giant in literature and in medical practice","volume":"13","author":"Bonheim","year":"1994","journal-title":"Lit Med"},{"issue":"10","key":"2024091719341162100_bnae014-B12","doi-asserted-by":"crossref","first-page":"2021","DOI":"10.1007\/s40618-021-01726-x","article-title":"The surprising Irish giant of St. James's street by Thomas Rowlandson. 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