Ectopic Cushing' syndrome caused by a neuroendocrine carcinoma of the mesentery
- Mathias Fasshauer†1,
- Thomas Lincke†2,
- Helmut Witzigmann3,
- Regine Kluge2,
- Andrea Tannapfel4,
- Michael Moche5,
- Michael Buchfelder6,
- Stephan Petersenn7,
- Juergen Kratzsch8,
- Ralf Paschke1 and
- Christian A Koch1, 9Email author
© Fasshauer et al; licensee BioMed Central Ltd. 2006
Received: 09 March 2006
Accepted: 27 April 2006
Published: 27 April 2006
ACTH overproduction within the pituitary gland or ectopically leads to hypercortisolism. Here, we report the first case of Cushing' syndrome caused by an ectopic ACTH-secreting neuroendocrine carcinoma of the mesentery. Moreover, diagnostic procedures and pitfalls associated with ectopic ACTH-secreting tumors are demonstrated and discussed.
A 41 year-old man presented with clinical features and biochemical tests suggestive of ectopic Cushing's syndrome. First, subtotal thyroidectomy was performed without remission of hypercortisolism, because an octreotide scan showed increased activity in the left thyroid gland and an ultrasound revealed nodules in both thyroid lobes one of which was autonomous. In addition, the patient had a 3 mm hypoenhancing lesion of the neurohypophysis and a 1 cm large adrenal tumor. Surgical removal of the pituitary lesion within the posterior lobe did not improve hypercortisolism and we continued to treat the patient with metyrapone to block cortisol production. At 18-months follow-up from initial presentation, we detected an ACTH-producing neuroendocrine carcinoma of the mesentery by using a combination of octreotide scan, computed tomography scan, and positron emission tomography. Intraoperatively, use of a gamma probe after administration of radiolabeled 111In-pentetreotide helped identify the mesenteric neuroendocrine tumor. After removal of this carcinoma, the patient improved clinically. Laboratory testing confirmed remission of hypercortisolism. An octreotide scan 7 months after surgery showed normal results.
This case underscores the diagnostic challenge in identifying an ectopic ACTH-producing tumor and the pluripotency of cells, in this case of mesenteric cells that can start producing and secreting ACTH. It thereby helps elucidate the pathogenesis of neuroendocrine tumors. This case also suggests that patients with ectopic Cushing's syndrome and an octreotide scan positive in atypical locations may benefit from explorative radioguided surgery using 111In-pentetreotide and a gamma probe.
Endocrine tumors can develop from a variety of tissue types and are often under- or misdiagnosed which underscores the difficulties to classify them. Ectopic ACTH overproduction not only leads to hypercortisolism but is also associated with various diagnostic and therapeutic pitfalls despite performing extensive diagnostic procedures.
Follow-up at four weeks and at 4 (7) months after surgery showed a normal 2 mg dexamethasone suppression test and 24 h urinary cortisol levels. Plasma ACTH levels were normal (4.9 and 5.2 pmol/L, normal: 1.8–12.8). NSE was 10.7 ng/ml (normal, < 13), chromogranin A and calcitonin were undetectable. In addition, the insulin requirement to treat the patient' s type 2 diabetes declined by more than 50%. At 7 month follow-up, the patient had regained strength and muscle mass, did not need further potassium replacement, and felt fine. An octreoscan showed normal results.
We present for the first time a case of EAS caused by a neuroendocrine carcinoma of the mesentery. Among ectopic ACTH-producing lesions, approximately 50% originate from intrathoracic tumors, usually small cell carcinomas [2–6]. Other well-described tumors of ectopic ACTH-production include medullary thyroid carcinoma, pheochromocytoma, as well as carcinomas of the thymus and pancreas [2, 7–11]. Except for the pancreas, other organs and locations for ACTH-producing tumors in the abdomen, i.e. appendix, duodenum, ileum, colon, anal canal, uterine cervix, and ovary are uncommon [12–20]. Endocrine tumors can develop from a variety of tissue types and are often under- or misdiagnosed which underscores the difficulties to classify them . Endocrine tumors may or may not produce and/or secrete hormones [22–32]. Mesenchymal tumors such as solitary fibrous tumors of the pleura, for instance, can lead to tumor hypoglycemia through production and secretion of pro-IGF-II [Fasshauer and Koch, unpublished observation; [33, 34]]. This ability of tumor cells making hormones is not surprising, if one considers the embryologic origin of tissues. For instance, upon induction, ectoderm of the blastula differentiates into mesodermal tissue such as chorda, muscle, and fibrous tissue. Without induction, however, ectoderm will differentiate into epidermis-like epithelium . Arita-Melzer et al.  reported a 76-yo man who suffered from Cushing's syndrome caused by ectopic ACTH production of a sacrococcygeal chordoma. In our patient, we propose that cells of the mesentery became malignant and started to produce ACTH ectopically. Although all removed lymph nodes were negative for tumor and the patient postoperatively became and remained eucortisolemic at 7 month follow-up, there is still a small chance that he harbors somewhere else a primary endocrine tumor producing ACTH that had metastasized to the mesentery. Another atypical location for primary endocrine tumors that had been controversially discussed for a long time is the liver. Maire et al.  has recently shown that this organ can harbor primary endocrine tumors, although the histogenesis of these tumors remains unknown. One hypothesis claims that pluripotent stem cells in the liver lead to primary endocrine tumors, a theory that is supported by a study showing that rat hepatic stem cells can differentiate into pancreatic functional endocrine cells . Another hypothesis assumes that these liver tumor cells are of neuroectodermal origin. In our patient, no liver lesions were seen. Primary endocrine tumors have also been reported in lymph nodes . In our patient, however, the removed tumor tissue and lymph nodes did not demonstrate evidence for lymph nodes as an origin of tumor growth.
Diagnosing EAS is often difficult [39, 40]. None of the dynamic biochemical tests achieves 100% accuracy, although BIPSS almost always shows an absent central gradient . A recent report by Ilias and co-workers emphasizes that 21 % and 26 % of patients with EAS have false-positive responses to dexamethasone and/or CRH . In their hands, IPSS is the single best test for EAS that correctly identified 66 out of 67 patients . In our case, all three independent tests suggested EAS, since a) the decline of serum cortisol was less than 50 % in the overnight 8-mg dexamethasone suppression test as compared to basal values, b) the increase in serum cortisol and plasma ACTH was less than 20 % and 35 %, respectively, after CRH stimulation, and c) IPSS demonstrated a less than 2-fold central-to-peripheral ACTH gradient basal and less than 3-fold gradient after CRH administration.
However, in the case presented, correct localization of tumor causing the EAS had been difficult. The percentage of tumors not identified despite extensive evaluation is between 12% and 19% [5, 6, 42]. In our case, imaging studies consisted of CT scans of chest, abdomen, and pelvis, an MRI scan of the pituitary, octreotide scans, and 18F-FDG PET at initial presentation and during follow-up. Except for PET, these tests are commonly used to locate the cause of EAS [2, 39, 43–47]. Furthermore, octreotide has been suggested not only as a diagnostic tool but also as second-line therapy in some cases of EAS [48, 49]. PET is a second-line diagnostic procedure when CT scan, MRI, and octreotide scan do not locate the cause of EAS . In the case presented, only the octreotide scan and the MRI of the pituitary had yielded pathological results at first presentation. Since EAS has been described in medullary thyroid carcinoma and the patient had multinodular goiter in association with hyperthyroidism, subtotal thyroidectomy was performed with the intention to exclude medullary thyroid carcinoma and resect the proven autonomous adenoma simultaneously in the face of a normal basal calcitonin and lacking pentagastrin stimulated calcitonin [8, 10]. However, this surgical procedure did not improve EAS. This result supports recent findings by Becker and co-workers that false-positive octreotide scans occur in endemic goiter with or without thyroid autonomy . Furthermore, it confirms recent reports indicating that a positive octreotide scan alone may not be sufficient to locate EAS . In our patient, the octreotide scan was also weakly positive in an abdominal area not very typical for an ACTH-producing endocrine tumor that later on, however, proved to be the cause for EAS. Similarly, an 111In-pentetreotide scan provided the decisive clue for locating a malignant ACTH-producing tumor of the ileum in a patient reported by Segu et al. . This suggests that patients with EAS and a positive octreoscan in locations atypical for an ACTH-producing tumor may benefit from explorative surgery using 111In-pentetreotide and a gamma probe.
Complicating the management of our patient with EAS and clearcut negative IPSS, a small lesion of the neurohypophysis was demonstrated at first presentation and during 1-year follow-up. False-negative results of IPPS in patients who do have an ACTH-producing pituitary tumor are reported to occur in up to 13% (7/127) . Given the increasingly difficult to control hypercortisolemia, the low risk of transsphenoidal surgery, and the recent findings of clinical researchers at the National Institutes of Health, where surgical removal of ACTHomas confined to the neurohypophysis resulted in remission of hypercortisolism in 12 patients , we decided to proceed with an exploration of the pituitary. However, in our case removal of the posterior lobe pituitary lesion did not result in remission of hypercortisolemia. These results re-emphasize the notion that a single positive imaging study may represent a falsely positive result, while more than one positive study in the same region may confirm a true ACTH-secreting lesion [2, 6]. It also underscores that in patients with Cushing's syndrome, dynamic biochemical testing is the most important step in establishing the diagnosis. Because our patient with EAS also had a left sided adrenal tumor in the setting of bilaterally enlarged adrenal glands, we measured 24 h urinary catecholamines including metanephrines to exclude an ACTH-producing pheochromocytoma which can occur in up to 25% of patients with EAS. In a recent study, 3 of 28 patients with ACTH-dependent Cushing's syndrome had focal adrenal nodules . Although non-catecholamine secreting pheochromocytomas have been described [9, 54], this is unlikely in our patient who had remission of hypercortisolism and ACTH production after the mesenterial tumor had been removed.
At 18-months after first presentation, another extensive diagnostic procedure was performed including CT scans of chest, abdomen, and pelvis, MRI head, octreotide scan, and 18F-FDG PET. Here, tracer accumulation in projection of the upper and middle part of the right abdomen was detectable in the octreotide scan and PET, for the first time corresponding to a 21 × 15 mm and 26 × 15 mm tumor mass on CT and MRI scans, respectively. These results support the view that regular follow-up of occult EAS may result in localization of ACTH production at later time points due to tumor growth [2, 6]. Furthermore, we could show that application of 111In-pentetreotide within hours before surgery facilitates localization of the tumor during surgery by use of radiolabeled 111In-pentetreotide and a gamma probe similar to recent reports [55, 56].
To further elucidate whether patients with neuroendocrine tumors that are (supposedly) completely resected, may benefit from adjuvant therapy including somatostatin analogs, we performed a MIB-1 proliferation index of the tumor in our patient and immunohistochemical analyses of somatostatin receptor expression [57, 58]. We found all 5 somatostatin receptors negative using immunohistochemistry [59, 60]. Especially the negative results for somatostatin receptor type 2 stand in contrast to our results on the octreoscans, although the tumor exceeded a size of 5 mm which is usually regarded as the detection limit for an octreoscan. These results may indicate that this ACTH-producing neuroendocrine tumor is very heterogeneous and/or somatostatin receptors were downregulated/saturated by intraoperative exposure to high doses of 111In-pentetreotide. Unfortunately, we were not able to assess mRNA for somatostatin receptor expression.
We report for the first time a patient with EAS due to a neuroendocrine carcinoma of the mesentery. This case not only may help elucidate the pathogenesis of (ACTH-producing) endocrine tumors, but also illustrates diagnostic pitfalls in the management of patients with EAS, and suggests that patients with EAS and an octreoscan positive in atypical locations may benefit from explorative radioguided surgery using a gamma probe.
inferior petrosal sinus sampling
magnetic resonance imaging
positron emission tomography
We thank all physicians and nurses who were involved in the clinical care for this patient. We thank especially Drs. A.O.Vortmeyer and E.H. Oldfield at the National Institutes of Health, Bethesda, MD, for offering their help in managing this patient. We also thank Novartis Pharma GmbH for supporting Dr. Koch in his efforts in elucidating the pathogenesis of neuroendocrine tumors. The antibodies for immunhistochemical detection of somatostatin receptors were kindly provided by Stefan Schulz.
- Weil RJ, DeVroom HL, Vortmeyer AO, Nieman LK, Oldfield EH: Adenomas Confined to the Neurohypophysis in Cushings Disease. Endocrine Society Meeting San Diego CA. 2005, P2-526.Google Scholar
- Wajchenberg BL, Mendonca BB, Liberman B, Pereira MA, Carneiro PC, Wakamatsu A, Kirschner MA: Ectopic adrenocorticotropic hormone syndrome. Endocr Rev. 1994, 15: 752-787. 10.1210/er.15.6.752.PubMedGoogle Scholar
- Phan GY, Yeo CJ, Hruban RH, Lillemoe KD, Pitt HA, Cameron JL: Surgical experience with pancreatic and peripancreatic neuroendocrine tumors: review of 125 patients. J Gastrointest Surg. 1998, 2: 472-482. 10.1016/S1091-255X(98)80039-5.View ArticlePubMedGoogle Scholar
- Koch CA, Doppman JL, Watson JC, Patronas NJ, Nieman LK: Spinal epidural lipomatosis in a patient with the ectopic corticotropin syndrome. N Engl J Med. 1999, 341: 1399-1400. 10.1056/NEJM199910283411814.View ArticlePubMedGoogle Scholar
- Aniszewski JP, Young WF, Thompson GB, Grant CS, van Heerden JA: Cushing syndrome due to ectopic adrenocorticotropic hormone secretion. World J Surg. 2001, 25: 934-940. 10.1007/s00268-001-0032-5.View ArticlePubMedGoogle Scholar
- Ilias I, Torpy DJ, Pacak K, Mullen N, Wesley RA, Nieman LK: Cushing's syndrome due to ectopic corticotropin secretion: twenty years' experience at the National Institutes of Health. J Clin Endocrinol Metab. 2005, 90: 4955-4962. 10.1210/jc.2004-2527.View ArticlePubMedGoogle Scholar
- Doppman JL, Nieman LK, Cutler GB, Chrousos GP, Fraker DL, Norton JA, Jensen RT: Adrenocorticotropic hormone-secreting islet cell tumors: are they always malignant ?. Radiology. 1994, 190: 59-64.View ArticlePubMedGoogle Scholar
- Mure A, Gicquel C, Abdelmoumene N, Tenenbaum F, Francese C, Travagli JP, Gardet P, Schlumberger M: Cushing's syndrome in medullary thyroid carcinoma. J Endocrinol Invest. 1995, 18: 180-185.View ArticlePubMedGoogle Scholar
- Alvarez P, Isidro L, Gonzales-Martin M, Loidi L, Arnal F, Cordido F: Ectopic adrenocorticotropic hormone production by a noncatecholamine secreting pheochromocytoma. J Urol. 2002, 167: 2514-2515. 10.1016/S0022-5347(05)65017-3.View ArticlePubMedGoogle Scholar
- Smallridge RC, Bourne K, Pearson BW, van Heerden JA, Carpenter PC, Young WF: Cushing's syndrome due to medullary thyroid carcinoma: diagnosis by proopiomelanocortin messenger ribonucleic acid in situ hybridization. J Clin Endocrinol Metab. 2003, 88: 4565-4568. 10.1210/jc.2002-021796.View ArticlePubMedGoogle Scholar
- Miehle K, Tannapfel A, Lamesch P, Borte G, Schenker E, Kluge R, Ott RA, Wiechmann V, Koch M, Kassahun W, Paschke R, Koch CA: Pancreatic neuroendocrine tumor with ectopic adrenocorticotropin production upon second recurrence. J Clin Endocrinol Metab. 2004, 89: 3731-3736. 10.1210/jc.2003-032164.View ArticlePubMedGoogle Scholar
- Bankole DO, Bertino JR, Cyne EA, Coonce M: Ectopic Cushing's syndrome in cloagenic carcinoma of the anal canal: a case demonstrating APUD characteristics. Yale J Biol Med. 1980, 53: 543-553.PubMedPubMed CentralGoogle Scholar
- Anthoney DA, Dunlop DJ, Connell JM, Kaye SB: Colonic adenocarcinoma associated ectopic ACTH secretion: a case history. Eur J Cancer. 1995, 31A: 2109-2112. 10.1016/0959-8049(95)00388-6.View ArticlePubMedGoogle Scholar
- Dobnig H, Stepan V, Leb G, Wolf G, Buchfelder M, Krejs GJ: Recovery from severe osteoporosis following cure from ectopic ACTH syndrome caused by an appendix carcinoid. J Intern Med. 1996, 239: 365-369. 10.1046/j.1365-2796.1996.416763000.x.View ArticlePubMedGoogle Scholar
- Segu VB, Mahvi DM, Wilson MA, Hale SJ, Warner TF, Meredith M, Shenker Y: Use of In-111 pentetreotide scintigraphy in the diagnosis of a midgut carcinoid causing Cushing's syndrome. Eur J Endocrinol. 1997, 137: 79-83. 10.1530/eje.0.1370079.View ArticlePubMedGoogle Scholar
- Uecker JM, Janzow MT: A case of Cushing syndrome secondary to ectopic adrenocorticotropic hormone producing carcinoid of the duodenum. Am Surg. 2005, 71: 445-446.PubMedGoogle Scholar
- Valo I, Rohmer V, Guyetant S, Martin JF, Venault S, Saint-Andre JP: Cushing's syndrome caused by a well-differentiated ileal neuroendocrine carcinoma. Endocr Pathol. 2000, 11: 359-364. 10.1385/EP:11:4:359.View ArticlePubMedGoogle Scholar
- Onishi R, Sano T, Nakamura Y, Namiuchi S, Sawada S, Ihara C, Shimatsu A: Ectopic adrenocorticotropin syndrome associated with undifferentiated carcinoma of the colon showing multidirectional neuroendocrine, exocrine, and squamous differentiation. Virchows Arch. 1996, 427: 537-541. 10.1007/BF00199515.View ArticlePubMedGoogle Scholar
- Hashi A, Yasmizu T, Yoda I, Kou T, Mizuno K, Hirata S, Kato J, Katoh R, Inoue M, Kawaguchi A, Nakazato M, Onaya T: A case of small cell carcinoma of the uterine cervix presenting Cushing's syndrome. Gynecol Oncol. 1996, 61: 427-431. 10.1006/gyno.1996.0168.View ArticlePubMedGoogle Scholar
- Orbetzova M, Andreeva M, Zacharieva S, Ivanova R, Dashev G: Ectopic ACTH-syndrome due to ovarian carcinoma. Exp Clin Endocrinol Diabetes. 1997, 105: 363-365.View ArticlePubMedGoogle Scholar
- Solcia E, Kloppel G, Sobin LH: Histological typing of endocrine tumours. 2000, Springer, Berlin, Heidelberg, New York, 2View ArticleGoogle Scholar
- DeBold CR, Menefee JK, Nicholson WE, Orth DN: Proopiomelanocortin gene is expressed in many normal human tissues and in tumors not associated with ectopic adrenocorticotropin syndrome. Mol Endocrinol. 1998, 2: 862-870.View ArticleGoogle Scholar
- Vortmeyer AO, Lubensky IA, Merino MJ, Wang CY, Pham T, Furth EE, Zhuang Z: Concordance of genetic alterations in poorly differentiated colorectal neuroendocrine carcinomas and associated adenocarcinomas. J Natl Cancer Inst. 1997, 89: 1448-53. 10.1093/jnci/89.19.1448.View ArticlePubMedGoogle Scholar
- Arita-Melzer O, Medina H, Borsotto G, Gamboa A, Larriva-Sahd J, Trejo G, Cardenas S, Aguilar-Salinas CA, Rull JA, Gomez-Perez FJ: An ectopic adrenocorticotropic hormone syndrome caused by a sacrococcygeal chordoma: report of a case with a slow progression. Endocr Pract. 1998, 4: 37-40.View ArticlePubMedGoogle Scholar
- Arioglu E, Gottlieb NA, Koch CA, Doppman JL, Grey NJ, Gorden P: Natural history of a proinsulin-secreting insulinom: from symptomatic hypoglycemia to clinical diabetes. J Clin Endocrinol Metab. 2000, 85: 3628-3630. 10.1210/jc.85.10.3628.View ArticlePubMedGoogle Scholar
- Witzigmann H, Loracher C, Geissler F, Wagner T, Tannapfel A, Uhlmann D, Caca K, Hauss J, Hehl JA: Neuroendocrine tumours of the duodenum. Clinical aspects, pathomorphology, and therapy. Langenbeck's Arch Surg. 2002, 386: 525-533. 10.1007/s00423-001-0260-z.View ArticleGoogle Scholar
- Pelte MF, Schwaller J, Cerrato C, Meier CA: Proopiomelanocortin expression in a metastatic breast carcinoma with ectopic ACTH secretion. Breast J. 2004, 10: 350-354. 10.1111/j.1075-122X.2004.21467.x.View ArticlePubMedGoogle Scholar
- Yu J, Koch CA, Patsalides A, Chang R, Altemus RM, Nieman LK, Pacak K: Ectopic Cushing's syndrome caused by an esthesioneuroblastoma. Endocr Pract. 2004, 10: 119-124.View ArticlePubMedGoogle Scholar
- Koch CA, Azumi N, Furlong MA, Jha RC, Kehoe TE, Trowbridge CH, O'Dorisio TM, Chrousos GP, Clement SC: Carcinoid syndrome caused by an atypical carcinoid of the uterine cervix. J Clin Endocrinol Metab. 1999, 84: 4209-4213. 10.1210/jc.84.11.4209.View ArticlePubMedGoogle Scholar
- Koch CA, Brouwers FM, Rosenblatt K, Burman KD, Davis MM, Vortmeyer AO, Pacak K: Adrenal ganglioneuroma in a patient presenting with severe hypertension and diarrhea. Endocr Rel Cancer. 2003, 10: 99-107. 10.1677/erc.0.0100099.View ArticleGoogle Scholar
- Koch CA, Rodbard JS, Brouwers FM, Eisenhofer G, Pacak K: Hypotension in a woman with metastatic dopamine-secreting carotid body tumor. Endocr Pract. 2003, 9: 310-314.View ArticlePubMedGoogle Scholar
- Koch CA, Pacak K, Chrousos GP: Endocrine Tumors. Principles and practice of pediatric oncology. Edited by: Pizzo P & Poplack DG. 2005, Lippincott Williams & Wilkins, Philadelphia, PA, 5Google Scholar
- Koch CA, Rother KI, Roth J: Tumor hypoglycaemia linked to IGF-II. Contemporary Endocrinology: The IGF System. Edited by: Rosenfeld R, Roberts C. 1999, Humana Press Inc, Totowa, NJ, 675-698.Google Scholar
- LeRoith D: Tumor-induced hypoglycaemia. N Engl J Med. 1999, 341: 757-758. 10.1056/NEJM199909023411011.View ArticleGoogle Scholar
- Nieukoop PD: Pattern formation in artificially activated ectoderm. Dev Biol. 1963, 7: 255-279. 10.1016/0012-1606(63)90122-2.View ArticleGoogle Scholar
- Maire F, Couvelard A, Vullierme MP, Kianmanesh R, O'Toole D, Hammel P, Belghiti J, Ruszniewski P: Primary endocrine tumours of the liver. Br J Surg. 2005, 92: 1255-1260. 10.1002/bjs.5073.View ArticlePubMedGoogle Scholar
- Yang L, Li S, Hatch H, Ahrens K, Cornelius JG, Petersen BE, Peck AB: In vitro trans-differentiation of adult hepatic stem cells into pancreatic endocrine hormone-producing cells. Proc Natl Acad Sci USA. 2002, 99: 8078-8083. 10.1073/pnas.122210699.View ArticlePubMedPubMed CentralGoogle Scholar
- Perrier ND, Batt KP, Thompson GB, Grant CS, Plummer TB: An immunohistochemical survey for neuroendocrine cells in regional pancreatic lymph nodes: a plausible explanation for primary nodal gastrinomas ? The Mayo Clinic Pancreatic Surgery Group. Surgery. 1995, 118: 957-965.View ArticlePubMedGoogle Scholar
- Arnaldi G, Angeli A, Atkinson , Bertagna X, Cavagnini F, Chrousos GP, Fava GA, Findling JW, Gaillard RC, Grossman AB, Kola B, Lacroix A, Mancini T, Mantero F, Newell-Price J, Nieman LK, Sonino N, Vance ML, Giustina A, Boscaro M: Diagnosis and complications of Cushing's syndrome: a consensus statement. J Clin Endocrinol Metab. 2003, 88: 5593-5602. 10.1210/jc.2003-030871.View ArticlePubMedGoogle Scholar
- Raff H, Findling JW: A physiological approach to diagnosis of the Cushing's syndrome. Ann Intern Med. 2003, 138: 980-991.View ArticlePubMedGoogle Scholar
- Isidori AM, Kaltsas GA, Pozza C, Frajese V, Newell-Price J, Reznek RH, Jenkins PJ, Monson JP, Grossman AB, Besser GM: The ectopic adrenocorticotropin syndrome: clinical features, diagnosis, management, and longterm follow-up. J Clin Endocrinol Metab. 2006, 91: 371-377. 10.1210/jc.2005-1542.View ArticlePubMedGoogle Scholar
- Findling JW, Tyrrell JB: Occult ectopic secretion of corticotropin. Arch Intern Med. 1986, 146: 929-933. 10.1001/archinte.146.5.929.View ArticlePubMedGoogle Scholar
- Pacak K, Eisenhofer G, Goldstein DS: Functional imaging of endocrine tumors: role of positron emission tomography. Endocr Rev. 2004, 25: 568-580. 10.1210/er.2003-0032.View ArticlePubMedGoogle Scholar
- Pacak K, Ilias I, Chen CC, Carrasquillo JA, Whatley M, Nieman LK: The role of 18F-FDG positron emission tomography and 111-In-pentetreotide scintigraphy in the localization of ectopic adrenocorticotropin-secreting tumors causing Cushing's syndrome. J Clin Endocrinol Metab. 2004, 89: 2214-2221. 10.1210/jc.2003-031812.View ArticlePubMedGoogle Scholar
- Biering H, Pirlich M, Bauditz J, Sandrock D, Lochs H, Gerl H: PET scan in occult ectopic ACTH syndrome: a useful tool?. Clin Endocrinol. 2003, 59: 404-405. 10.1046/j.1365-2265.2003.01853.x.View ArticleGoogle Scholar
- Bombardieri E, Maccauro M, De Deckere E, Savelli G, Chiti A: Nuclear medicine imaging of neuroendocrine tumours. Ann Oncol Suppl. 2001, 2: S51-61. 10.1023/A:1012488727716.View ArticleGoogle Scholar
- Kaltsas G, Rockall A, Papadogias D, Reznek R, Grossman AB: Recent advances in radiological and radionuclide imaging and therapy of neuroendocrine tumours. Eur J Endocrinol. 2004, 151: 15-27. 10.1530/eje.0.1510015.View ArticlePubMedGoogle Scholar
- von Werder K, Muller OA, Stalla GK: Somatostatin analogs in ectopic corticotropin production. Metabolism. 1996, 45: 129-131. 10.1016/S0026-0495(96)90107-9.View ArticlePubMedGoogle Scholar
- Uwaifo GI, Koch CA, Hirshberg B, Chen CC, Hartzband P, Nieman LK, Pacak K: Is there a therapeutic role for octreotide in patients with ectopic Cushing's syndrome?. J Endocrinol Invest. 2003, 26: 710-717.View ArticlePubMedGoogle Scholar
- Becker W, Schrell U, Buchfelder M, Hensen J, Wendler J, Gramatzki M, Wolf F: Somatostatin receptor expression in the thyroid demonstrated with 111In-octreotide scintigraphy. Nuklearmedizin. 1995, 34: 100-103.PubMedGoogle Scholar
- Krakoff J, Koch CA, Calis KA, Alexander RH, Nieman LK: Use of a parenteral propylene glycol-containing etomidate preparation for the long-term management of ectopic Cushing' s syndrome. J Clin Endocrinol Metab. 2001, 86: 4104-4108. 10.1210/jc.86.9.4104.PubMedGoogle Scholar
- Swearingen B, Katznelson L, Miller K, Grinspoon S, Waltman A, Dorer DJ, Klibanski A, Biller B: Diagnostic errors after inferior petrosal sinus sampling. J Clin Endocrinol Metab. 2004, 89: 3752-3763. 10.1210/jc.2003-032249.View ArticlePubMedGoogle Scholar
- Imaki T, Naruse M, Takano K: Adrenocortical hyperplasia associated with ACTH-dependent Cushing's syndrome: comparison of the size of adrenal glands with clinical and endocrinological data. Endocr J. 2004, 51: 89-95. 10.1507/endocrj.51.89.View ArticlePubMedGoogle Scholar
- Walther MM, Reiter R, Keiser HR, Choyke PL, Venzon D, Hurley K, Gnarra JR, Reynolds JC, Glenn GM, Zbar B, Linehan WM: Clinical and genetic characterization of pheochromocytoma in von Hippel-Lindau families: comparison with sporadic pheochromocytoma gives insight into natural history of pheochromocytoma. J Urol. 1999, 162: 659-664. 10.1097/00005392-199909010-00004.View ArticlePubMedGoogle Scholar
- Filippi L, Valentini FB, Gossetti B, Gossetti F, De Vincentis G, Scopinaro F, Massa R: Intraoperative gamma probe detection of head and neck paragangliomas with 111In-pentetreotide: a pilot study. Tumori. 2005, 91: 173-176.PubMedGoogle Scholar
- Grossrubatscher E, Vignati F, Dalino P, Possa M, Belloni PA, Vanzulli A, Bramerio M, Marocchi A, Rossetti O, Zurleni F, Loli P: Use of radioguided surgery with [111In]-pentetreotide in the management of an ACTH-secreting bronchial carcinoid causing ectopic Cushing's syndrome. J Endocrinol Invest. 2005, 28: 72-78.View ArticlePubMedGoogle Scholar
- Janson ET, Oberg K: Neuroendocrine tumors-somatostatin receptor expression and somatostatin analog treatment. Cancer Chemother Biol Response Modif. 2003, 21: 535-546.View ArticlePubMedGoogle Scholar
- Plockinger U, Rindi G, Arnold R, Eriksson B, Krenning EP, de Herder WW, Goede A, Caplin M, Oberg K, Reubi JC, Nilsson O, Delle Fave G, Ruszniewski P, Ahlman H, Wiedenmann B: Guidelines for the diagnosis and treatment of neuroendocrine gastointestinal tumours. A consensus statement on behalf of the European Neuroendocrine Tumour Society (ENETS). Neuroendocrinology. 2004, 80: 394-424. 10.1159/000085237.View ArticlePubMedGoogle Scholar
- Unger N, Serdiuk I, Sheu SY, Walz MK, Schulz S, Schmid KW, Mann K, Petersenn S: Immunohistochemical determination of somatostatin receptor subtypes 1, 2, 3, 4, and 5 in various adrenal tumors. Endocrine Res. 2004, 30: 931-934. 10.1081/ERC-200044161.View ArticleGoogle Scholar
- Kristiansen MT, Rasmussen LM, Olsen N, Jorgenson JO: Ectopic ACTH syndrome: discrepancy between somatostatin receptor status in vivo and ex vivo, and between immunostaining and gene transcription for POMC and CRH. Horm Res. 2002, 57: 200-204. 10.1159/000058383.View ArticlePubMedGoogle Scholar
- The pre-publication history for this paper can be accessed here:http://www.biomedcentral.com/1471-2407/6/108/prepub
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