{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,19]],"date-time":"2026-03-19T06:23:41Z","timestamp":1773901421075,"version":"3.50.1"},"reference-count":127,"publisher":"Oxford University Press (OUP)","issue":"3","license":[{"start":{"date-parts":[[2023,2,28]],"date-time":"2023-02-28T00:00:00Z","timestamp":1677542400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2023,3,2]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Thirty years ago, we identified that cortisol secretion in some patients with unilateral adenoma or primary bilateral macronodular adrenal hyperplasia (PBMAH) was stimulated by food intake; this was secondary to the abnormal adrenocortical responsiveness to physiological post-prandial increase in glucose-dependent insulinotropic peptide (GIP). This resulted from the ectopic expression of non-mutated GIP receptor in the pathological adrenal tissues of those patients. Although ectopic GIP receptor (GIPR) was confirmed in a relatively limited number of cases to date, its elucidation leads to the identification of a wide diversity of aberrant G-protein-coupled receptors regulating steroidogenesis and cell proliferation in a high proportion of patients with PBMAH or cortisol-secreting adenomas. In addition, ectopic GIPR was identified in other endocrine tumors including somatotroph pituitary tumors with paradoxical growth hormone response to oral glucose, medullary thyroid carcinomas, and other neuroendocrine tumors. The first molecular pathogenic mechanism responsible for ectopic GIPR expression was elucidated in unilateral GIP\u2013dependent adenomas in which somatic duplication and rearrangements in chromosome region 19q13.32 containing the GIPR locus lead to increased expression of GIPR which was enhanced by the activity of a glucocorticoid response element. Recently, germline lysine demythylase 1A (KDMIA) mutations combined with somatic chromosome 1p deletions were found to be specifically responsible for ectopic GIPR in sporadic or familial GIP\u2013dependent PBMAH and can be associated with adrenal myelolipoma, monoclonal gammopathy of unknown significance (MGUS), or multiple myeloma. Screening for ectopic GIPR should be conducted in all patients with PBMAH; genetic studies to identify KDM1A mutations should be offered to such patients in order to detect affected members and provide early detection of PBMAH and other potential associated neoplasias. The elucidation of GIP\u2013dependent Cushing's syndrome (CS) illustrates that careful bedside phenotyping of rare conditions can lead to identification of genetically determined diseases requiring personalized approaches to investigation and therapy.<\/jats:p>","DOI":"10.1093\/ejendo\/lvad026","type":"journal-article","created":{"date-parts":[[2023,3,1]],"date-time":"2023-03-01T16:35:33Z","timestamp":1677688533000},"page":"R56-R72","source":"Crossref","is-referenced-by-count":16,"title":["Extensive expertise in endocrinology: glucose-dependent insulinotropic peptide\u2013dependent Cushing's syndrome"],"prefix":"10.1093","volume":"188","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4137-3025","authenticated-orcid":false,"given":"Andr\u00e9","family":"Lacroix","sequence":"first","affiliation":[{"name":"Division of Endocrinology, Department of Medicine and Research Center, Centre hospitalier de l\u2019Universit\u00e9 de Montr\u00e9al (CHUM) , Montr\u00e9al, Qu\u00e9bec H2X 0A9 , Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2023,2,28]]},"reference":[{"issue":"9996","key":"2023033115541288800_","doi-asserted-by":"crossref","first-page":"913","DOI":"10.1016\/S0140-6736(14)61375-1","article-title":"Cushing's syndrome","volume":"386","author":"Lacroix","year":"2015","journal-title":"Lancet"},{"issue":"6","key":"2023033115541288800_","doi-asserted-by":"crossref","first-page":"R249","DOI":"10.1530\/EJE-15-1118","article-title":"Endocrine tumours: the genomics of adrenocortical tumors","volume":"174","author":"Faillot","year":"2016","journal-title":"Eur J Endocrinol"},{"issue":"9","key":"2023033115541288800_","doi-asserted-by":"crossref","DOI":"10.1210\/jendso\/bvaa075","article-title":"Molecular basis of primary aldosteronism and adrenal Cushing syndrome","volume":"4","author":"Vaduva","year":"2020","journal-title":"J Endocr 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