{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,9,11]],"date-time":"2025-09-11T20:32:51Z","timestamp":1757622771024,"version":"3.44.0"},"reference-count":34,"publisher":"Georg Thieme Verlag KG","issue":"08","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Exp Clin Endocrinol Diabetes"],"published-print":{"date-parts":[[2025,8]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Aberrant expression of glucose-dependent insulinotropic peptide receptors\n                        (GIPR) might regulate increased steroidogenesis in patients with\n                        ACTH-independent cortisol hypersecretion. This study investigated the\n                        presence of aberrant GIPR expression in patients with ACTH-independent\n                        cortisol hypersecretion and bilateral adrenal adenomas.<\/jats:p><jats:p>Patients with bilateral adrenal adenomas, ACTH-independent CS and aberrant\n                        GIPR screened via mixed meal test were included. Patients\u2019 demographic\n                        features and laboratory and imaging findings were obtained\n                        retrospectively.<\/jats:p><jats:p>Twenty-one patients were included. Overt CS findings were present in 14.3% of\n                        the patients. One patient (4.7%) had a complete positive response (537%\n                        increase) and one patient (4.7%) had a partial response (41% increase) to\n                        the mixed meal test. In the remaining 19 patients, a mean change of -10.1%\n                        (range: \u221256.5% to+24.7%) in cortisol levels was observed at 120 min compared\n                        to baseline. The patient with a complete positive response was confirmed\n                        using 100 \u00b5g of IV octreotide. The patient underwent unilateral\n                        adrenalectomy after an inadequate long-term response to octreotide LAR\n                        therapy. The histopathology revealed bilateral macronodular adrenal cortical\n                        disease. We identified a germline heterozygous frameshift variant in the\n                        KDM1A gene in the patient\u2019s blood sample and a recurrent deletion of the p\n                        arm of chromosome 1 harboring the KDM1A locus in the adrenal sample.<\/jats:p><jats:p>These results may provide useful insights into the screening of aberrant GIPR\n                        expression in patients with ACTH-independent hypercortisolism. It is\n                        essential to further investigate which patients require screening. Moreover,\n                        a significant cortisol peak observed during the mixed meal test in the\n                        presence of these receptors has drawn attention.<\/jats:p>","DOI":"10.1055\/a-2676-1138","type":"journal-article","created":{"date-parts":[[2025,9,8]],"date-time":"2025-09-08T22:30:24Z","timestamp":1757370624000},"page":"408-414","source":"Crossref","is-referenced-by-count":0,"title":["Experience with the Mixed Meal Test in Diagnosing GIP-Dependent\n                    Cortisol Hypersecretion at a Tertiary Center"],"prefix":"10.1055","volume":"133","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0042-6928","authenticated-orcid":false,"given":"Tugba","family":"Barlas","sequence":"additional","affiliation":[{"name":"Endocrinology and Metabolism, Gazi University, Ankara,\n                    Turkey"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4286-243X","authenticated-orcid":false,"given":"Gulsum","family":"Kayhan","sequence":"additional","affiliation":[{"name":"Medical Genetics, Gazi University, Ankara,\n                    Turkey"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1041-6881","authenticated-orcid":false,"given":"Mehmet Muhittin","family":"Yalcin","sequence":"additional","affiliation":[{"name":"Endocrinology and Metabolism, Gazi University, Ankara,\n                    Turkey"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7518-388X","authenticated-orcid":false,"given":"Ethem Turgay","family":"Cerit","sequence":"additional","affiliation":[{"name":"Endocrinology and Metabolism, Gazi University, Ankara,\n                    Turkey"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0457-6560","authenticated-orcid":false,"given":"Mujde","family":"Akturk","sequence":"additional","affiliation":[{"name":"Endocrinology and Metabolism, Gazi University, Ankara,\n                    Turkey"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6168-937X","authenticated-orcid":false,"given":"Fusun Balos","family":"Toruner","sequence":"additional","affiliation":[{"name":"Endocrinology and Metabolism, Gazi University, Ankara,\n                    Turkey"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2573-3927","authenticated-orcid":false,"given":"Sinan","family":"Sozen","sequence":"additional","affiliation":[{"name":"Urology, Gazi University, Ankara, Turkey"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3316-3020","authenticated-orcid":false,"given":"Aylar","family":"Poyraz","sequence":"additional","affiliation":[{"name":"Pathology, Gazi University, Ankara, Turkey"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0601-6893","authenticated-orcid":false,"given":"Ayhan","family":"Karako\u00e7","sequence":"additional","affiliation":[{"name":"Endocrinology and Metabolism, Gazi University, Ankara,\n                    Turkey"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6707-7761","authenticated-orcid":false,"given":"Alev Eroglu","family":"Altinova","sequence":"additional","affiliation":[{"name":"Endocrinology and Metabolism, Gazi University, Ankara,\n                    Turkey"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"194","published-online":{"date-parts":[[2025,9,8]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","first-page":"947","DOI":"10.1210\/jcem-24-10-947","article-title":"Cushing\u2019s syndrome: Nodular Cortical hyperplasia of adrenal glands with clinical\n                    and pathological features suggesting adrenocortical tumor","volume":"24","author":"M A Kirschner","year":"1964","journal-title":"J Clin Endocrinol Metab"},{"key":"ref2","doi-asserted-by":"publisher","first-page":"R567","DOI":"10.1530\/erc-19-0240","article-title":"Diagnosis and management of primary bilateral macronodular adrenal\n                    hyperplasia","volume":"26","author":"D A Vassiliadi","year":"2019","journal-title":"Endocr Relat Cancer"},{"key":"ref3","doi-asserted-by":"crossref","first-page":"567","DOI":"10.1210\/endrev\/bnac034","article-title":"Clinical, pathophysiologic, genetic, and therapeutic progress in primary\n                    bilateral macronodular adrenal hyperplasia","volume":"44","author":"J Bertherat","year":"2023","journal-title":"Endocr Rev"},{"key":"ref4","doi-asserted-by":"publisher","first-page":"2930","DOI":"10.1210\/jc.2009-0516","article-title":"Clinical and genetic heterogeneity, overlap with other tumor syndromes, and\n                    atypical glucocorticoid hormone secretion in adrenocorticotropin-independent\n                    macronodular adrenal hyperplasia compared with other adrenocortical tumors","volume":"94","author":"H P Hsiao","year":"2009","journal-title":"J Clin Endocrinol Metab"},{"key":"ref5","doi-asserted-by":"publisher","first-page":"311","DOI":"10.1111\/j.1365-2265.2004.02048.x","article-title":"Aberrant adrenal sensitivity to multiple ligands in unilateral incidentaloma\n                    with subclinical autonomous cortisol hypersecretion: A prospective clinical\n                    study","volume":"61","author":"Y Reznik","year":"2004","journal-title":"Clin Endocrinol"},{"key":"ref6","doi-asserted-by":"publisher","first-page":"129","DOI":"10.1530\/eje-10-0195","article-title":"Aberrant cortisol regulations in bilateral macronodular adrenal hyperplasia: A\n                    frequent finding in a prospective study of 32 patients with overt or subclinical\n                    Cushing\u2019s syndrome","volume":"163","author":"R Lib\u00e9","year":"2010","journal-title":"Eur J Endocrinol"},{"key":"ref7","doi-asserted-by":"publisher","first-page":"3531","DOI":"10.1210\/jcem.85.10.6865","article-title":"Are ectopic or abnormal membrane hormone receptors frequently present in adrenal\n                    Cushing\u2019s syndrome?","volume":"85","author":"H Mircescu","year":"2000","journal-title":"J Clin Endocrinol Metab"},{"key":"ref8","doi-asserted-by":"publisher","first-page":"2105","DOI":"10.1056\/NEJMoa1304603","article-title":"ARMC5 mutations in macronodular adrenal hyperplasia with Cushing's\n                    syndrome","volume":"369","author":"G Assi\u00e9","year":"2013","journal-title":"N Engl J Med"},{"key":"ref9","doi-asserted-by":"publisher","first-page":"E926","DOI":"10.1210\/jc.2014-4204","article-title":"ARMC5 mutations in a large cohort of primary macronodular adrenal hyperplasia:\n                    Clinical and functional consequences","volume":"100","author":"S Espiard","year":"2015","journal-title":"J Clin Endocrinol Metab"},{"key":"ref10","doi-asserted-by":"publisher","first-page":"E1113","DOI":"10.1210\/jc.2013-4280","article-title":"Macronodular adrenal hyperplasia due to mutations in an armadillo repeat\n                    containing 5 (ARMC5) gene: A clinical and genetic investigation","volume":"99","author":"F R Faucz","year":"2014","journal-title":"J Clin Endocrinol Metab"},{"key":"ref11","doi-asserted-by":"publisher","first-page":"123","DOI":"10.1530\/eje-21-1032","article-title":"Identification of predictive criteria for pathogenic variants of primary\n                    bilateral macronodular adrenal hyperplasia (PBMAH) gene ARMC5 in 352 unselected\n                    patients","volume":"187","author":"L Bouys","year":"2022","journal-title":"Eur J Endocrinol"},{"key":"ref12","doi-asserted-by":"publisher","first-page":"85","DOI":"10.1530\/eje-15-0642","article-title":"ARMC5 mutations in a large French-Canadian family with cortisol-secreting\n                    \u03b2-adrenergic\/vasopressin responsive bilateral macronodular adrenal\n                    hyperplasia","volume":"174","author":"I Bourdeau","year":"2016","journal-title":"Eur J Endocrinol"},{"key":"ref13","doi-asserted-by":"publisher","first-page":"813","DOI":"10.1016\/s2213-8587(21)00236-9","article-title":"Loss of KDM1A in GIP-dependent primary bilateral macronodular adrenal\n                    hyperplasia with Cushing\u2019s syndrome: A multicentre, retrospective, cohort\n                    study","volume":"9","author":"F Chasseloup","year":"2021","journal-title":"Lancet Diabetes Endocrinol"},{"key":"ref14","doi-asserted-by":"publisher","first-page":"245","DOI":"10.1016\/j.beem.2008.10.011","article-title":"ACTH-independent macronodular adrenal hyperplasia","volume":"23","author":"A Lacroix","year":"2009","journal-title":"Best Pract Res Clin Endocrinol Metab"},{"key":"ref15","doi-asserted-by":"publisher","first-page":"595","DOI":"10.1007\/s12020-021-02645-w","article-title":"Update on primary bilateral macronodular adrenal hyperplasia (PBMAH","volume":"71","author":"L Bouys","year":"2021","journal-title":"Endocrine"},{"key":"ref16","doi-asserted-by":"crossref","first-page":"R56","DOI":"10.1093\/ejendo\/lvad026","article-title":"Extensive expertise in endocrinology: Glucose-dependent insulinotropic\n                    peptide\u2013dependent Cushing's syndrome","volume":"188","author":"A Lacroix","year":"2023","journal-title":"Eur J Endocrinol"},{"key":"ref17","doi-asserted-by":"publisher","first-page":"618","DOI":"10.3389\/fendo.2019.00618","article-title":"Coexistence of myelolipoma and primary bilateral macronodular adrenal\n                    hyperplasia with GIP-dependent Cushing\u2019s syndrome","volume":"10","author":"S Larose","year":"2019","journal-title":"Front Endocrinol (Lausanne)"},{"key":"ref18","doi-asserted-by":"publisher","first-page":"287","DOI":"10.1055\/s-0030-1270523","article-title":"Transient efficacy of octreotide and pasireotide (SOM230) treatment in\n                    GIP-dependent Cushing's syndrome","volume":"43","author":"V Preumont","year":"2011","journal-title":"Horm Metab Res"},{"key":"ref19","doi-asserted-by":"crossref","first-page":"e77","DOI":"10.4158\/EP12346.CR","article-title":"Adrenocorticotropic hormone independent macronodular adrenal hyperplasia due to\n                    aberrant receptor expression: Is medical treatment always an option?","volume":"19","author":"O Karapanou","year":"2013","journal-title":"Endocrine Practice"},{"key":"ref20","doi-asserted-by":"publisher","first-page":"2616","DOI":"10.1210\/jcem.84.8.5930","article-title":"Asynchronous development of bilateral nodular adrenal hyperplasia in gastric\n                    inhibitory polypeptide-dependent Cushing\u2019s syndrome","volume":"84","author":"N N'Diaye","year":"1999","journal-title":"J Clin Endocrinol Metab"},{"key":"ref21","doi-asserted-by":"publisher","first-page":"697","DOI":"10.1055\/a-2359-8051","article-title":"From the first case reports to KDM1A identification: 35 years of food\n                    (GIP)-dependent Cushing\u2019s syndrome","volume":"132","author":"L Bouys","year":"2024","journal-title":"Exp Clin Endocrinol Diabetes"},{"key":"ref22","doi-asserted-by":"publisher","first-page":"G1","DOI":"10.1093\/ejendo\/lvad066","article-title":"European Society of Endocrinology clinical practice guidelines on the management\n                    of adrenal incidentalomas, in collaboration with the European Network for the\n                    Study of Adrenal Tumors","volume":"189","author":"M Fassnacht","year":"2023","journal-title":"Eur J Endocrinol"},{"key":"ref23","doi-asserted-by":"publisher","first-page":"659","DOI":"10.1055\/a-2299-5065","article-title":"Subtyping of Cushing's syndrome: A step ahead","volume":"132","author":"I Tizianel","year":"2024","journal-title":"Exp Clin Endocrinol Diabetes"},{"key":"ref24","doi-asserted-by":"publisher","first-page":"75","DOI":"10.1210\/edrv.22.1.0420","article-title":"Ectopic and abnormal hormone receptors in adrenal Cushing\u2019s syndrome","volume":"22","author":"A Lacroix","year":"2001","journal-title":"Endocr Rev"},{"key":"ref25","doi-asserted-by":"publisher","first-page":"155","DOI":"10.1007\/s12022-022-09710-8","article-title":"Overview of the 2022 WHO classification of adrenal cortical tumors","volume":"33","author":"O Mete","year":"2022","journal-title":"Endocr Pathol"},{"key":"ref26","doi-asserted-by":"crossref","first-page":"797","DOI":"10.1148\/radiology.216.3.r00au40797","article-title":"Adrenocorticotropin-independent macronodular adrenal hyperplasia: An uncommon\n                    cause of primary adrenal hypercortisolism","volume":"216","author":"J L Doppman","year":"2000","journal-title":"Radiology"},{"key":"ref27","doi-asserted-by":"crossref","first-page":"771","DOI":"10.1530\/EJE-07-0253","article-title":"Food-dependent Cushing\u2019s syndrome: From molecular characterization to\n                    therapeutical results","volume":"157","author":"N Albiger","year":"2007","journal-title":"Eur J Endocrinol"},{"key":"ref28","doi-asserted-by":"crossref","first-page":"974","DOI":"10.1056\/NEJM199210013271402","article-title":"Gastric inhibitory polypeptide\u2013dependent cortisol hypersecretion\u2014A new cause of\n                    Cushing\u2019s syndrome","volume":"327","author":"A Lacroix","year":"1992","journal-title":"N Engl J Med"},{"key":"ref29","doi-asserted-by":"crossref","first-page":"981","DOI":"10.1056\/NEJM199210013271403","article-title":"Food-dependent Cushing\u2019s syndrome mediated by aberrant adrenal sensitivity to\n                    gastric inhibitory polypeptide","volume":"327","author":"Y Reznik","year":"1992","journal-title":"N Engl J Med"},{"key":"ref30","doi-asserted-by":"crossref","first-page":"1980","DOI":"10.1210\/jcem.87.5.8458","article-title":"The ectopic expression of the gastric inhibitory polypeptide receptor is\n                    frequent in adrenocorticotropin-independent bilateral macronodular adrenal\n                    hyperplasia, but rare in unilateral tumors","volume":"87","author":"L Groussin","year":"2002","journal-title":"J Clin Endocrinol Metab"},{"key":"ref31","doi-asserted-by":"publisher","first-page":"853","DOI":"10.1515\/jpem.2002.15.6.853","article-title":"An adolescent with food-dependent Cushing\u2019s syndrome secondary to ectopic\n                    expression of GIP receptor in unilateral adrenal adenoma","volume":"15","author":"C Noordam","year":"2002","journal-title":"J Pediatr Endocrinol Metab"},{"key":"ref32","doi-asserted-by":"publisher","first-page":"583","DOI":"10.1210\/jcem.86.2.7171","article-title":"Food-dependent androgen and cortisol secretion by a gastric inhibitory\n                    polypeptide-receptor expressive adrenocortical adenoma leading to hirsutism and\n                    subclinical Cushing\u2019s syndrome: In vivo and in vitro studies","volume":"86","author":"S Tsagarakis","year":"2001","journal-title":"J Clin Endocrinol Metab"},{"key":"ref33","doi-asserted-by":"publisher","first-page":"229","DOI":"10.1016\/j.endien.2023.04.005","article-title":"Primary bilateral macronodular adrenal hyperplasia: A series of 32 cases and\n                    literature review","volume":"70","author":"M Araujo-Castro","year":"2023","journal-title":"Endocrinol Diabetes Nutr"},{"key":"ref34","doi-asserted-by":"publisher","first-page":"334","DOI":"10.1093\/ejendo\/lvae106","article-title":"Primary unilateral macronodular adrenal hyperplasia with concomitant\n                    glucocorticoid and androgen excess and KDM1A inactivation","volume":"191","author":"Y S Elhassan","year":"2024","journal-title":"Eur J Endocrinol"}],"container-title":["Experimental and Clinical Endocrinology &amp; Diabetes"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/www.thieme-connect.de\/products\/ejournals\/pdf\/10.1055\/a-2676-1138.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,9,8]],"date-time":"2025-09-08T22:30:27Z","timestamp":1757370627000},"score":1,"resource":{"primary":{"URL":"http:\/\/www.thieme-connect.de\/DOI\/DOI?10.1055\/a-2676-1138"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,8]]},"references-count":34,"journal-issue":{"issue":"08","published-online":{"date-parts":[[2025,9,8]]},"published-print":{"date-parts":[[2025,8]]}},"URL":"https:\/\/doi.org\/10.1055\/a-2676-1138","archive":["Portico","CLOCKSS"],"relation":{},"ISSN":["0947-7349","1439-3646"],"issn-type":[{"type":"print","value":"0947-7349"},{"type":"electronic","value":"1439-3646"}],"subject":[],"published":{"date-parts":[[2025,8]]}}}