{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,20]],"date-time":"2026-07-20T14:17:23Z","timestamp":1784557043740,"version":"3.55.0"},"reference-count":58,"publisher":"Bioscientifica","content-domain":{"domain":["edm.bioscientifica.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2015,3,1]]},"abstract":"Summary<\/jats:title>\n \n Ectopic ACTH Cushing's syndrome (EAS) is often caused by neuroendocrine tumors (NETs) of lungs, pancreas, thymus, and other less frequent locations. Localizing the source of ACTH can be challenging. A 64-year-old man presented with rapidly progressing fatigue, muscular weakness, and dyspnea. He was in poor condition and showed facial redness, proximal amyotrophy, and bruises. Laboratory disclosed hypokalemia, metabolic alkalosis, and markedly elevated ACTH and cortisol levels. Pituitary was normal on magnetic resonance imaging (MRI), and bilateral inferior petrosal sinus blood sampling with corticotropin-releasing hormone stimulation showed no significant central-to-periphery gradient of ACTH. Head and neck, thoracic and abdominal computerized tomography (CT), MRI, somatostatin receptor scintigraphy (SSRS), and\n 18<\/jats:sup>\n F-deoxyglucose-positron emission tomography (FDG-PET) failed to identify the primary tumor.\n 18<\/jats:sup>\n F-dihydroxyphenylalanine (F-DOPA)-PET\/CT unveiled a 20-mm nodule in the jejunum and a metastatic lymph node. Segmental jejunum resection showed two adjacent NETs, measuring 2.0 and 0.5\u200acm with a peritoneal metastasis. The largest tumor expressed ACTH in 30% of cells. Following surgery, after a transient adrenal insufficiency, ACTH and cortisol levels returned to normal values and remain normal over a follow-up of 26 months. Small mid-gut NETs are difficult to localize on CT or MRI, and require metabolic imaging. Owing to low mitotic activity, NETs are generally poor candidates for FDG-PET, whereas SSRS shows poor sensitivity in EAS due to intrinsically low tumor concentration of type-2 somatostatin receptors (SST2) or to receptor down regulation by excess cortisol. However, F-DOPA-PET, which is related to amine precursor uptake by NETs, has been reported to have high positive predictive value for occult EAS despite low sensitivity, and constitutes a useful alternative to more conventional methods of tumor localization.\n <\/jats:p>\n \n Learning points<\/jats:title>\n \n \n \n Uncontrolled high cortisol levels in EAS can be lethal if untreated.<\/jats:p>\n <\/jats:list-item>\n \n Surgical excision is the keystone of NETs treatment, thus tumor localization is crucial.<\/jats:p>\n <\/jats:list-item>\n \n Most cases of EAS are caused by NETs, which are located mainly in the lungs. However, small gut NETs are elusive to conventional imaging and require metabolic imaging for detection.<\/jats:p>\n <\/jats:list-item>\n \n FDG-PET, based on tumor high metabolic rate, may not detect NETs that have low mitotic activity. SSRS may also fail, due to absent or low concentration of SST2, which may be down regulated by excess cortisol.<\/jats:p>\n <\/jats:list-item>\n \n F-DOPA-PET, based on amine-precursor uptake, can be a useful method to localize the occult source of ACTH in EAS when other methods have failed.<\/jats:p>\n <\/jats:list-item>\n <\/jats:list>\n <\/jats:p>\n <\/jats:sec>","DOI":"10.1530\/edm-14-0104","type":"journal-article","created":{"date-parts":[[2015,3,17]],"date-time":"2015-03-17T06:51:31Z","timestamp":1426575091000},"update-policy":"https:\/\/doi.org\/10.1530\/crossmarkpolicy-2","source":"Crossref","is-referenced-by-count":2,"title":["Mid-gut ACTH-secreting neuroendocrine tumor unmasked with 18F-dihydroxyphenylalanine-positron emission tomography"],"prefix":"10.1530","volume":"2015","author":[{"given":"Julien","family":"Ducry","sequence":"first","affiliation":[{"name":"1 Services of Endocrinology Diabetes and Metabolism, Lausanne University Hospital, Lausanne, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fulgencio","family":"Gomez","sequence":"additional","affiliation":[{"name":"1 Services of Endocrinology Diabetes and Metabolism, Lausanne University Hospital, Lausanne, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John O","family":"Prior","sequence":"additional","affiliation":[{"name":"2 Nuclear Medicine, Lausanne University Hospital, Lausanne, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ariane","family":"Boubaker","sequence":"additional","affiliation":[{"name":"2 Nuclear Medicine, Lausanne University Hospital, Lausanne, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maurice","family":"Matter","sequence":"additional","affiliation":[{"name":"3 Visceral Surgery, Lausanne University Hospital, Lausanne, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matteo","family":"Monti","sequence":"additional","affiliation":[{"name":"4 Internal Medicine, Lausanne University Hospital, Lausanne, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yan","family":"Pu","sequence":"additional","affiliation":[{"name":"5 Institute of Pathology, Lausanne University Hospital, Lausanne, CH-1011, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nelly","family":"Pitteloud","sequence":"additional","affiliation":[{"name":"1 Services of Endocrinology Diabetes and Metabolism, Lausanne University Hospital, Lausanne, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luc","family":"Portmann","sequence":"additional","affiliation":[{"name":"1 Services of Endocrinology Diabetes and Metabolism, Lausanne University Hospital, Lausanne, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"416","reference":[{"key":"ref551","doi-asserted-by":"crossref","first-page":"373","DOI":"10.1148\/radiology.220.2.r01au25373","article-title":"Whole-body 18F-Dopa PET for detection of gastrointestinal carcinoid tumors","volume":"220","year":"2001","journal-title":"Radiology"},{"key":"ref461","doi-asserted-by":"crossref","first-page":"173","DOI":"10.1007\/BF01468882","article-title":"Somatostatin: a potent inhibitor of ACTH hyper-secretion in adrenal insufficiency","volume":"54","year":"1976","journal-title":"Klinische Wochenschrift"},{"key":"ref11","doi-asserted-by":"crossref","first-page":"934","DOI":"10.1002\/cncr.11105","article-title":"A 5-decade analysis of 13,715 carcinoid tumors","volume":"97","year":"2003","journal-title":"Cancer"},{"key":"ref331","doi-asserted-by":"publisher","first-page":"168","DOI":"10.1530\/EJE-12-0418","article-title":"LepageCBouvierAM of malignant digestive neuroendocrine tumors of","author":"FaivreJ","year":"2013","journal-title":"Epidemiology European Journal Endocrinology"},{"key":"ref541","first-page":"1","article-title":"Utility of various functional and anatomic imaging modalities for detection of ectopic adrenocorticotropin-secreting tumors","volume":"95","year":"2010","journal-title":"Journal of Clinical Endocrinology and Metabolism"},{"key":"ref141","doi-asserted-by":"crossref","first-page":"524","DOI":"10.1055\/s-0029-1243634","article-title":"Ectopic Cushing's syndrome caused by a well differentiated ACTH-secreting neuroendocrine carcinoma of the ileum","volume":"118","year":"2010","journal-title":"Experimental and Clinical Endocrinology & Diabetes"},{"key":"ref01","doi-asserted-by":"crossref","first-page":"4381","DOI":"10.1002\/cncr.26029","article-title":"Cushing's syndrome secondary to ectopic adrenocorticotropic hormone secretion: the University of Texas MD Anderson Cancer Center Experience","volume":"117","year":"2011","journal-title":"Cancer"},{"key":"ref371","doi-asserted-by":"publisher","first-page":"39","DOI":"10.1007\/s00259-011-2039-y","article-title":"KamBLRTeunissenJJMKrennningEPde HerderWWKhanSvan Lutetium - 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