{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,8,15]],"date-time":"2025-08-15T02:34:01Z","timestamp":1755225241777,"version":"3.43.0"},"reference-count":22,"publisher":"The Endocrine Society","issue":"9","license":[{"start":{"date-parts":[[2025,8,1]],"date-time":"2025-08-01T00:00:00Z","timestamp":1754006400000},"content-version":"vor","delay-in-days":15,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025,7,17]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Episodic severe Cushing syndrome resulting from ectopic ACTH secretion (EAS) from appendiceal neuroendocrine tumor (NET) is extremely rare. Here, we describe a case of a 24-year-old woman with episodic severe EAS resulting from appendiceal NET with extensive metastatic disease. The patient presented with rapid weight gain, violaceous striae, fatigue, edema, and anxiety. Biochemical evaluation showed markedly elevated 24-hour urinary free cortisol greater than 10-fold above the upper limit of normal, and widely fluctuating peaks and troughs of serum cortisol and ACTH concentrations indicating episodic severe EAS. Surgery for primary malignancy was initially deferred because of the high risk of perioperative complications related to severe hypercortisolism. She underwent bilateral adrenalectomy as first-line definitive treatment for severe EAS. Four months after adrenalectomy, she underwent cytoreductive surgery for primary metastatic appendiceal NET. Subsequent peptide receptor radionuclide therapy and monthly lanreotide injections rendered her disease stable. Three years after the initial presentation, she continued to undergo active surveillance with maintenance lanreotide for residual but stable metastatic appendiceal neuroendocrine tumor. This case of a rare metastatic appendiceal NET with EAS demonstrates the importance of individualized management and highlights the need for consideration of prompt bilateral adrenalectomy for patients with severe Cushing syndrome.<\/jats:p>","DOI":"10.1210\/jcemcr\/luaf171","type":"journal-article","created":{"date-parts":[[2025,7,22]],"date-time":"2025-07-22T11:27:34Z","timestamp":1753183654000},"source":"Crossref","is-referenced-by-count":0,"title":["Episodic Severe Ectopic Adrenocorticotropic Hormone Syndrome by Metastatic Appendiceal Neuroendocrine Tumor"],"prefix":"10.1210","volume":"3","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0720-8416","authenticated-orcid":false,"given":"Ruchi","family":"Desai","sequence":"first","affiliation":[{"name":"Department of Internal Medicine, University of Texas Southwestern Medical Center , Dallas, TX 75390 ,","place":["USA"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"F N U","family":"Sidra","sequence":"additional","affiliation":[{"name":"Division of Endocrinology and Metabolism, University of Texas Southwestern Medical Center , Dallas, TX 75390 ,","place":["USA"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Liwei","family":"Jia","sequence":"additional","affiliation":[{"name":"Division of Pathology, University of Texas Southwestern Medical Center , Dallas, TX 75390 ,","place":["USA"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1719-1208","authenticated-orcid":false,"given":"Patricio M","family":"Polanco","sequence":"additional","affiliation":[{"name":"Division of Surgical Oncology, University of Texas Southwestern Medical Center , Dallas, TX 75390 ,","place":["USA"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Salwan","family":"Al Mutar","sequence":"additional","affiliation":[{"name":"Division of Hematology\/Oncology, University of Texas Southwestern Medical Center , Dallas, TX 75390 ,","place":["USA"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7367-3885","authenticated-orcid":false,"given":"Oksana","family":"Hamidi","sequence":"additional","affiliation":[{"name":"Division of Endocrinology and Metabolism, University of Texas Southwestern Medical Center , Dallas, TX 75390 ,","place":["USA"]}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"80","published-online":{"date-parts":[[2025,8,1]]},"reference":[{"issue":"3","key":"2025081304265983500_luaf171-B1","doi-asserted-by":"crossref","first-page":"383","DOI":"10.1530\/EJE-11-0272","article-title":"The European Registry on Cushing's syndrome: 2-year experience. Baseline demographic and clinical characteristics","volume":"165","author":"Valassi","year":"2011","journal-title":"Eur J Endocrinol"},{"issue":"1","key":"2025081304265983500_luaf171-B2","first-page":"7159696","article-title":"Demographic characteristics, etiology, and comorbidities of patients with Cushing's syndrome: a 10-year retrospective study at a large general hospital in China","volume":"2019","author":"Zhou","year":"2019","journal-title":"Int J Endocrinol"},{"issue":"9996","key":"2025081304265983500_luaf171-B3","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":"2","key":"2025081304265983500_luaf171-B4","doi-asserted-by":"crossref","first-page":"170","DOI":"10.1001\/jama.2023.11305","article-title":"Cushing syndrome: a review","volume":"330","author":"Reincke","year":"2023","journal-title":"JAMA"},{"issue":"8","key":"2025081304265983500_luaf171-B5","doi-asserted-by":"crossref","first-page":"1217","DOI":"10.1590\/S0004-27302007000800007","article-title":"Ectopic ACTH syndrome","volume":"51","author":"Isidori","year":"2007","journal-title":"Arq Bras Endocrinol Metabol"},{"issue":"1","key":"2025081304265983500_luaf171-B6","doi-asserted-by":"crossref","first-page":"19","DOI":"10.2214\/AJR.16.17290","article-title":"Cushing syndrome: diagnostic workup and imaging features, with clinical and pathologic correlation","volume":"209","author":"Wagner-Bartak","year":"2017","journal-title":"AJR Am J Roentgenol"},{"issue":"19","key":"2025081304265983500_luaf171-B7","doi-asserted-by":"crossref","first-page":"4381","DOI":"10.1002\/cncr.26029","article-title":"Cushing syndrome secondary to ectopic adrenocorticotropic hormone secretion: the University of Texas MD Anderson Cancer Center Experience","volume":"117","author":"Ejaz","year":"2011","journal-title":"Cancer"},{"issue":"8","key":"2025081304265983500_luaf171-B8","doi-asserted-by":"crossref","first-page":"4955","DOI":"10.1210\/jc.2004-2527","article-title":"Cushing's syndrome due to ectopic corticotropin secretion: twenty years\u2019 experience at the National Institutes of Health","volume":"90","author":"Ilias","year":"2005","journal-title":"J Clin Endocrinol Metab"},{"issue":"2","key":"2025081304265983500_luaf171-B9","doi-asserted-by":"crossref","first-page":"371","DOI":"10.1210\/jc.2005-1542","article-title":"The ectopic adrenocorticotropin syndrome: clinical features, diagnosis, management, and long-term follow-up","volume":"91","author":"Isidori","year":"2006","journal-title":"J Clin Endocrinol Metab"},{"issue":"5","key":"2025081304265983500_luaf171-B10","doi-asserted-by":"crossref","first-page":"725","DOI":"10.1530\/eje.1.02278","article-title":"Ectopic ACTH syndrome: our experience with 25 cases","volume":"155","author":"Salgado","year":"2006","journal-title":"Eur J Endocrinol"},{"key":"2025081304265983500_luaf171-B11","doi-asserted-by":"crossref","first-page":"808199","DOI":"10.3389\/fendo.2022.808199","article-title":"Appendiceal neuroendocrine tumor is a rare cause of ectopic adrenocorticotropic hormone syndrome with cyclic hypercortisolism: a case report and literature review","volume":"13","author":"Zhao","year":"2022","journal-title":"Front Endocrinol (Lausanne)"},{"issue":"7","key":"2025081304265983500_luaf171-B12","doi-asserted-by":"crossref","first-page":"949","DOI":"10.1007\/s00384-010-1073-8","article-title":"Cushing's syndrome cured by resection of an appendiceal carcinoid tumor","volume":"26","author":"Beddy","year":"2011","journal-title":"Int J Colorectal Dis"},{"issue":"6","key":"2025081304265983500_luaf171-B13","doi-asserted-by":"crossref","first-page":"770","DOI":"10.1001\/archsurg.1971.01350120134028","article-title":"Cushing's syndrome cured by resection of appendiceal carcinoid","volume":"103","author":"Miller","year":"1971","journal-title":"Arch Surg"},{"issue":"11","key":"2025081304265983500_luaf171-B14","doi-asserted-by":"crossref","first-page":"642","DOI":"10.1038\/ncpendmet0327","article-title":"Cushing's syndrome caused by an occult source: difficulties in diagnosis and management","volume":"2","author":"Grossman","year":"2006","journal-title":"Nat Clin Pract Endocrinol Metab"},{"issue":"11","key":"2025081304265983500_luaf171-B15","doi-asserted-by":"crossref","first-page":"881","DOI":"10.1097\/RLU.0000000000002766","article-title":"68Ga-DOTATATE PET\/CT of ectopic cushing syndrome due to appendicular carcinoid","volume":"44","author":"Diwaker","year":"2019","journal-title":"Clin Nucl Med"},{"issue":"4","key":"2025081304265983500_luaf171-B16","doi-asserted-by":"crossref","first-page":"365","DOI":"10.1046\/j.1365-2796.1996.416763000.x","article-title":"Recovery from severe osteoporosis following cure from ectopic ACTH syndrome caused by an appendix carcinoid","volume":"239","author":"Dobnig","year":"1996","journal-title":"J Intern Med"},{"issue":"1","key":"2025081304265983500_luaf171-B17","doi-asserted-by":"crossref","first-page":"141","DOI":"10.1515\/jpem-2020-0442","article-title":"Ectopic ACTH production by thymic and appendiceal neuroendocrine tumors\u2013two case reports","volume":"34","author":"Moszczy\u0144ska","year":"2021","journal-title":"J Pediatr Endocrinol Metab"},{"issue":"(09|9)","key":"2025081304265983500_luaf171-B18","first-page":"525","article-title":"Ectopic ACTH-syndrome due to a neuroendocrine tumour of the appendix","volume":"119","author":"Perakakis","year":"2011","journal-title":"Exp Clin Endocrinol Diabetes"},{"issue":"8","key":"2025081304265983500_luaf171-B19","doi-asserted-by":"crossref","first-page":"593","DOI":"10.1016\/S2213-8587(23)00150-X","article-title":"Diagnostic challenges in cyclic Cushing's syndrome: a systematic review","volume":"11","author":"Nowak","year":"2023","journal-title":"Lancet Diabetes Endocrinol"},{"issue":"3","key":"2025081304265983500_luaf171-B20","doi-asserted-by":"crossref","first-page":"245","DOI":"10.1530\/EJE-07-0262","article-title":"Cyclic Cushing's syndrome: a clinical challenge","volume":"157","author":"Meinardi","year":"2007","journal-title":"Eur J Endocrinol"},{"issue":"8","key":"2025081304265983500_luaf171-B21","doi-asserted-by":"crossref","first-page":"2807","DOI":"10.1210\/jc.2015-1818","article-title":"Treatment of Cushing's syndrome: an endocrine society clinical practice guideline","volume":"100","author":"Nieman","year":"2015","journal-title":"J Clin Endocrinol Metab"},{"issue":"4","key":"2025081304265983500_luaf171-B22","doi-asserted-by":"crossref","first-page":"453","DOI":"10.1530\/EJE-16-0809","article-title":"Prognostic factors in ectopic Cushing's syndrome due to neuroendocrine tumors: a multicenter study","volume":"176","author":"Davi","year":"2017","journal-title":"Eur J Endocrinol"}],"container-title":["JCEM Case Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/jcemcr\/article-pdf\/3\/9\/luaf171\/63919474\/luaf171.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/jcemcr\/article-pdf\/3\/9\/luaf171\/63919474\/luaf171.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,8,13]],"date-time":"2025-08-13T08:27:12Z","timestamp":1755073632000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/jcemcr\/article\/doi\/10.1210\/jcemcr\/luaf171\/8220834"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,7,17]]},"references-count":22,"journal-issue":{"issue":"9","published-print":{"date-parts":[[2025,7,17]]}},"URL":"https:\/\/doi.org\/10.1210\/jcemcr\/luaf171","relation":{},"ISSN":["2755-1520"],"issn-type":[{"type":"electronic","value":"2755-1520"}],"subject":[],"published-other":{"date-parts":[[2025,9]]},"published":{"date-parts":[[2025,7,17]]},"article-number":"luaf171"}}