Skip to main content

The ectopic ACTH syndrome

Abstract

Ectopic Cushing’s syndrome usually relates to the ectopic ACTH syndrome (EAS) and represents ∼20% of ACTH-dependent and ∼10% of all types of Cushing’s syndrome (CS). Nearly any neuroendocrine or non-endocrine tumours may be associated with EAS, but the more prevalent tumours are bronchial carcinoids, small cell lung carcinomas, pancreatic carcinoids, thymic carcinoids, medullary carcinomas of the thyroid, and phaeochromocytomas. Occult tumours are highly represented in all the series (12–38%) and constitute the more challenging cases of EAS, requiring long term follow-up. The lack of any completely reliable diagnostic test procedure and imaging to clearly reveal the source of EAS suggests that we should adopt a step-by-step multidisciplinary approach for their diagnosis and therapeutic management. Clinical features are often similar in ACTH-dependent CS, but the rapid onset and progress may suggest an ectopic source. A combination of biochemical tests and imaging studies seems the most appropriate approach for the prompt identification of EAS, even if there are several pitfalls to be avoided along the way. The most appropriate management for cure of EAS, when its source is identified, is surgical excision after controlling the hypercortisolaemia by inhibitors of cortisol secretion and other newer modalities alone or in combination; bilateral adrenalectomy remains an alternative option. Tumour histology, the presence of metastases and the effective control of hypercortisolaemia affect mortality and morbidity. If a source repeatedly fails to be found, the prognosis is often favourable but the identification of a malignant tumour should still be sought during life-long follow-up to avoid the calamity of misdiagnosis.

This is a preview of subscription content, access via your institution.

Abbreviations

BIPSS:

Bilateral inferior petrosal sinus sampling

CRH:

Corticotropin-releasing hormone

EAS:

ACTH ectopic syndrome

FDG-PET:

[18F]Flurodeoxyglucose positron emission tomography

HDDST:

High-dose dexamethasone test

LDDST:

Low-dose dexamethasone test

MTC:

Medullary carcinoma of the thyroid

NETs:

Neuroendocrine tumours

NSE:

Neuron-specific enolase

Octreoscan:

111In-octreotide scintigraphy

POMC:

Pro-opiomelanocortin

SCLC:

Small cell lung carcinoma

SSAs:

Somatostatin analogues

References

  1. 1.

    Newell-Price J, Bertagna X, Grossman AB, Nieman LK. Cushing’s syndrome. Lancet 2006;367:1605–17.

    CAS  Article  PubMed  Google Scholar 

  2. 2.

    Isidori AM, Kaltsas GA, Pozza C, Frajese V, Newell-Price J, Reznek RH, et al. The ectopic adrenocorticotrophin syndrome: clinical features, diagnosis, management and long-term follow-up. J Clin Endocrinol Metab. 2006;91:371–7.

    CAS  Article  PubMed  Google Scholar 

  3. 3.

    Aniszewski JP, Young Jr WF, Thompson GB, Grant CS, van Heerden JA. Cushing syndrome due to ectopic adrenocorticotropic hormone secretion. World J Surg. 2001;25:934–40.

    CAS  Article  PubMed  Google Scholar 

  4. 4.

    Imura H, Matsukura S, Yamamoto H, Hirata Y, Nakai Y. Studies on ectopic ACTH-producing tumors. II. Clinical and biochemical features of 30 cases. Cancer 1975;35:1430–7.

    CAS  Article  PubMed  Google Scholar 

  5. 5.

    Liddle GW, Nicholson WE, Island DP, Orth DN, Abe K, Lowder SC. Clinical and laboratory studies of ectopic humoral syndromes. Recent Prog Horm Res. 1969;25:283–314.

    CAS  PubMed  Google Scholar 

  6. 6.

    Jex RK, van Heerden JA, Carpenter PC, Grant CS. Ectopic ACTH syndrome. Diagnostic and therapeutic aspects. Am J Surg. 1985;149:276–82.

    CAS  Article  PubMed  Google Scholar 

  7. 7.

    Howlett TA, Drury PL, Perry L, Doniach I, Rees LH, Besser GM. Diagnosis and management of ACTH-dependent Cushing’s syndrome: comparison of the features in ectopic and pituitary ACTH production. Clin Endocrinol (Oxf). 1986;24:699–713.

    CAS  Article  Google Scholar 

  8. 8.

    Doppman JL, Nieman L, Miller DL, Pass HI, Chang R, Cutler Jr GB, et al. Ectopic adrenocorticotropic hormone syndrome: localization studies in 28 patients. Radiology 1989;172:115–24.

    CAS  PubMed  Google Scholar 

  9. 9.

    Wajchenberg BL, Mendonça B, Liberman B, Adelaide M, Pereira A, Kirschner MA. Ectopic ACTH syndrome. J Steroid Biochem Mol Biol. 1995;53:139–51.

    CAS  Article  PubMed  Google Scholar 

  10. 10.

    Tabarin A, Valli N, Chanson P, Bachelot Y, Rohmer V, Bex-Bachellerie V, et al. Usefulness of somatostatin receptor scintigraphy in patients with occult ectopic adrenocorticotropin syndrome. J Clin Endocrinol Metab. 1999;84:1193–202.

    CAS  Article  PubMed  Google Scholar 

  11. 11.

    Torpy DJ, Mullen N, Ilias I, Nieman LK. Association of hypertension and hypokalemia with Cushing’s syndrome caused by ectopic ACTH secretion: a series of 58 cases. Ann NY Acad Sci. 2002;970:134–44.

    CAS  Article  PubMed  Google Scholar 

  12. 12.

    Hernández I, Espinosa-de-los-Monteros AL, Mendoza V, Cheng S, Molina M, Sosa E, et al. Ectopic ACTH-secreting syndrome: a single center experience report with a high prevalence of occult tumor. Arch Med Res. 2006;37:976–80.

    Article  PubMed  Google Scholar 

  13. 13.

    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;90:4955–62.

    CAS  Article  PubMed  Google Scholar 

  14. 14.

    Salgado LR, Fragoso MC, Knoepfelmacher M, Machado MC, Domenice S, Pereira MA, et al. Ectopic ACTH syndrome: our experience with 25 cases. Eur J Endocrinol. 2006;155:725–33.

    CAS  Article  PubMed  Google Scholar 

  15. 15.

    Bhansali A, Walia R, Rana SS, Dutta P, Radotra BD, Khandelwal N, et al. Ectopic Cushing’s syndrome: experience from a tertiary care centre. Indian J Med Res. 2009;129:33–41.

    CAS  PubMed  Google Scholar 

  16. 16.

    Wajchenberg BL, Mendonca BB, Liberman B, Pereira MA, Carneiro PC, Wakamatsu A, et al. Ectopic adrenocorticotropic hormone syndrome. Endocr Rev. 1994;15:752–87.

    CAS  PubMed  Google Scholar 

  17. 17.

    Beuschlein F, Hammer GD. Ectopic pro-opiomelanocortin syndrome. Endocrinol Metab Clin N Am. 2002;31:191–234.

    CAS  Article  Google Scholar 

  18. 18.

    Isidori AM, Kaltsas GA, Grossman AB. Ectopic ACTH syndrome. Front Horm Res. 2006;35:143–56.

    CAS  Article  PubMed  Google Scholar 

  19. 19.

    Isidori AM, Lenzi A. Ectopic ACTH syndrome. Arq Bras Endocrinol Metabol. 2007;51:1217–25.

    PubMed  Google Scholar 

  20. 20.

    Salvatori R. Ectopic Cushing’s syndrome: some facts. Indian J Med Res. 2009;129:4–6.

    PubMed  Google Scholar 

  21. 21.

    Sarlis NJ, Chanock SJ, Nieman LK. Cortisolemic indices predict severe infections in Cushing syndrome due to ectopic production of adrenocorticotropin. J Clin Endocrinol Metab. 2000;85:42–7.

    CAS  Article  PubMed  Google Scholar 

  22. 22.

    Newell-Price J, Trainer P, Besser GM, Grossman A. The diagnosis and differential diagnosis of Cushing’s syndrome and pseudo-Cushing’s states. Endocr Rev. 1998;19:647–72.

    CAS  Article  PubMed  Google Scholar 

  23. 23.

    Isidori AM, Kaltsas GA, Mohammed S, Morris DG, Jenkins P, Chew SL, et al. Discriminatory value of the low-dose dexamethasone suppression test in establishing the diagnosis and differential diagnosis of Cushing’s syndrome. J Clin Endocrinol Metab. 2003;88:5299–306.

    CAS  Article  PubMed  Google Scholar 

  24. 24.

    Vilar L, Freitas Mda C, Faria M, Montenegro R, Casulari LA, Naves L, et al. Pitfalls in the diagnosis of Cushing’s syndrome. Arq Bras Endocrinol Metabol. 2007;51:1207–16.

    PubMed  Google Scholar 

  25. 25.

    Vilar L, Naves LA, Freitas MC, Moura E, Canadas V, Leal E, et al. Endogenous Cushing’s syndrome: clinical and laboratorial features in 73 cases. Arq Bras Endocrinol Metabol. 2007;51:566–74.

    PubMed  Google Scholar 

  26. 26.

    Kaye TB, Crapo L. The Cushing syndrome: an update on diagnostic tests. Ann Intern Med. 1990;112:434–44.

    CAS  PubMed  Google Scholar 

  27. 27.

    Meier CA, Biller BMK. Clinical and biochemical evaluation of Cushing’s syndrome. Endocrinol Metab Clin N Am. 1997;26:741–62.

    CAS  Article  Google Scholar 

  28. 28.

    Invitti C, Giraldi FP, de Martin M, Cavagnini F. Diagnosis and management of Cushing’s syndrome: results of an Italian multicentre study. Study group of the Italian Society of Endocrinology on the pathophysiology of the hypothalamic-pituitaryadrenal axis. J Clin Endocrinol Metab. 1999;84:440–8.

    CAS  Article  PubMed  Google Scholar 

  29. 29.

    Nieman LK, Oldfield EH, Wesley R, Chrousos GP, Loriaux DL, Cutler Jr GB. A simplified morning ovine corticotropin-releasing hormone stimulation test for the differential diagnosis of adrenocorticotropin-dependent Cushing’s syndrome. J Clin Endocrinol Metab. 1993;77:1308–12.

    CAS  Article  PubMed  Google Scholar 

  30. 30.

    Newell-Price J, Morris DG, Drake WM, Drake WM, Korbonits M, Monson JP, et al. Optimal response criteria for the human CRH test in the differential diagnosis of ACTH-dependent Cushing’s syndrome. J Clin Endocrinol Metab. 2002;87:1640–5.

    CAS  Article  PubMed  Google Scholar 

  31. 31.

    Terzolo M, Reimondo G, Ali A, Borretta G, Cesario F, Pia A, et al. The limited value of the desmopressin test in the diagnostic approach to Cushing’s syndrome. Clin Endocrinol (Oxf). 2001;54:609–16.

    CAS  Article  Google Scholar 

  32. 32.

    Castinetti F, Morange I, Dufour H, Jaquet P, Conte-Devolx B, Girard N, et al. Desmopressin test during petrosal sinus sampling: a valuable tool to discriminate pituitary or ectopic ACTH-dependent Cushing’s syndrome. Eur J Endocrinol. 2007;157:271–7.

    CAS  Article  PubMed  Google Scholar 

  33. 33.

    Kaltsas GA, Giannulis MG, Newell-Price JD, Dacie JE, Thakkar C, Afshar F, et al. A critical analysis of the value of simultaneous inferior petrosal sinus sampling in Cushing’s disease and the occult ectopic adrenocorticotropin syndrome. J Clin Endocrinol Metab. 1999;84:487–92.

    CAS  Article  PubMed  Google Scholar 

  34. 34.

    Swearingen B, Katznelson L, Miller K, Grinspoon S, Waltman A, Dorer DJ, et al. Diagnostic errors after inferior petrosal sinus sampling. J Clin Endocrinol Metab. 2004;89:3752–63.

    CAS  Article  PubMed  Google Scholar 

  35. 35.

    Oldfield EH, Doppman JL, Nieman LK, Chrousos GP, Miller DL, Katz DA, et al. Petrosal sinus sampling with and without corticotropin-releasing hormone for the differential diagnosis of Cushing’s syndrome. N Engl J Med. 1991;325:897–905.

    CAS  Article  PubMed  Google Scholar 

  36. 36.

    Yamamoto Y, Davis DH, Nippoldt TB, Young Jr WF, Huston III J, Parisi JE. False-positive inferior petrosal sinus sampling in the diagnosis of Cushing’s disease. Report of two cases. J Neurosurg. 1995;83:1087–91.

    CAS  Article  PubMed  Google Scholar 

  37. 37.

    Nieman LK, Chrousos GP, Oldfield EH, Avgerinos PC, Cutler Jr GB, Loriaux DL. The ovine corticotropin-releasing hormone stimulation test and the dexamethasone suppression test in the differential diagnosis of Cushing’s syndrome. Ann Intern Med. 1986;105:862–7.

    CAS  PubMed  Google Scholar 

  38. 38.

    Ghigo E, Arvat E, Ramunni J, Colao A, Gianotti L, Deghenghi R, et al. Adrenocorticotropin-and cortisolreleasing effect of hexarelin, a synthetic growth hormonereleasing peptide, in normal subjects and patients with Cushing’s syndrome. J Clin Endocrinol Metab. 1997;82:2439–44.

    CAS  Article  PubMed  Google Scholar 

  39. 39.

    Doppman JL, Pass HI, Nieman LK, Miller DL, Chang R, Cutler Jr GB, et al. Corticotropin-secreting carcinoid tumors of the thymus: diagnostic unreliability of thymic venous sampling. Radiology 1992;184:71–4.

    CAS  PubMed  Google Scholar 

  40. 40.

    Kuhn JM, Proeschel MF, Seurin DJ, Bertagna XY, Luton JP, Girard FL. Comparative assessment of ACTH and lipotropin plasma levels in the diagnosis and follow-up of patients with Cushing’s syndrome: a study of 210 cases. Am J Med. 1989;86:678–84.

    CAS  Article  PubMed  Google Scholar 

  41. 41.

    Tabarin A, Corcuff JB, Rashedi M, Navarranne A, Ducassou D, Roger P. Comparative value of plasma ACTH and beta-endorphin measurement with three different commercial kits for the etiological diagnosis of ACTH-dependent Cushing’s syndrome. Acta Endocrinol (Copenh). 1992;126:308–14.

    CAS  Google Scholar 

  42. 42.

    Raffin-Sanson ML, Massias JF, Dumont C, Raux-Demay MC, Proeschel MF, Luton JP, et al. High plasma proopiomelanocortin in aggressive adrenocorticotropin-secreting tumors. J Clin Endocrinol Metab. 1996;81:4272–7.

    CAS  Article  PubMed  Google Scholar 

  43. 43.

    Van Sickle DG. Carcinoid tumors. Analysis of 61 cases, including 11 cases of carcinoid syndrome. Cleve Clin Q. 1972;39:79–86.

    PubMed  Google Scholar 

  44. 44.

    Grossman AB, Kelly P, Rockall A, Bhattacharya S, McNicol A, Barwick T. Cushing’s syndrome caused by an occult source: difficulties in diagnosis and management. Nat Clin Pract Endocrinol Metab. 2006;2:642–7.

    Article  PubMed  Google Scholar 

  45. 45.

    Torpy DJ, Chen CC, Mullen N, Doppman JL, Carrasquillo JA, Chrousos GP, et al. Lack of utility of (111)In-pentetreotide scintigraphy in localizing ectopic ACTH producing tumors: follow-up of 18 patients. J Clin Endocrinol Metab. 1999;84:1186–92.

    CAS  Article  PubMed  Google Scholar 

  46. 46.

    Reincke M, Allolio B, Arlt W, Körber C. Comment on primary localization of an ectopic ACTH-producing bronchial carcinoid tumor by indium111 pentetreotide scintigraphy. J Clin Endocrinol Metab. 1999;84:3399–400.

    CAS  Article  PubMed  Google Scholar 

  47. 47.

    Silva F, Vázquez-Sellés J, Aguilö F, Vázquez G, Flores C. Recurrent ectopic adrenocorticotropic hormone producing thymic carcinoid detected with octreotide imaging. Clin Nucl Med. 1999;24:109–10.

    CAS  Article  PubMed  Google Scholar 

  48. 48.

    De Herder WW, Lamberts SW. Octapeptide somatostatin-analogue therapy of Cushing’s syndrome. Postgrad Med J. 1999;75:65–6.

    PubMed  Google Scholar 

  49. 49.

    Fanti S, Farsad M, Battista G, Monetti F, Montini GC, Chiti A, et al. Somatostatin receptor scintigraphy for bronchial carcinoid follow-up. Clin Nucl Med. 2003;28:548–52.

    Article  PubMed  Google Scholar 

  50. 50.

    Tsagarakis S, Christoforaki M, Giannopoulou H, Rondogianni F, Housianakou I, Malagari C, et al. A reappraisal of the utility of somatostatin receptor scintigraphy in patients with ectopic adrenocorticotropin Cushing’s syndrome. J Clin Endocrinol Metab. 2003;88:4754–8.

    CAS  Article  PubMed  Google Scholar 

  51. 51.

    Pacak K, Ilias I, Chen CC, Carrasquillo JA, Whatley M, Nieman LK. The role of [(18)F]fluorodeoxyglucose positron emission tomography and [(111)In]-diethylenetriaminepentaacetate-D-Phe-pentetreotide scintigraphy in the localization of ectopic adrenocorticotropin-secreting tumors causing Cushing’s syndrome. J Clin Endocrinol Metab. 2004;89:2214–21.

    CAS  Article  PubMed  Google Scholar 

  52. 52.

    Aide N, Reznik Y, Icard P, Franson T, Bardet S. Paraneoplastic ACTH secretion: bronchial carcinoid overlooked by planar indium-111 pentetreotide scintigraphy and accurately localized by SPECT/CT acquisition. Clin Nucl Med. 2007;32:398–400.

    Article  PubMed  Google Scholar 

  53. 53.

    Adams S, Baum RP, Stuckensen T, Bitter K, Hor G. Prospective comparison of 18F-FDG PET with conventional imaging modalities (CT, MRI, US) in lymph node staging of head and neck cancer. Eur J Nucl Med. 1998;25:1255–60.

    CAS  Article  PubMed  Google Scholar 

  54. 54.

    Kumar J, Spring M, Carroll PV, Barrington SF, Powrie JK. 18Flurodeoxyglucose positron emission tomography in the localization of ectopic ACTH-secreting neuroendocrine tumours. Clin Endocrinol (Oxf). 2006;64:371–4.

    CAS  Google Scholar 

  55. 55.

    Markou A, Manning P, Kaya B, Datta SN, Bomanji JB, Conway GS. [18F]fluoro-2-deoxy-D-glucose ([18F]FDG) positron emission tomography imaging of thymic carcinoid tumor presenting with recurrent Cushing’s syndrome. Eur J Endocrinol. 2005;152:521–5.

    CAS  Article  PubMed  Google Scholar 

  56. 56.

    Moreno-Fernández J, Gutiérrez-Alcántara C, Gálvez Moreno MA, Jiménez-Reina L, Castaño JP, Benito-López P. Corticotrophin-dependent Cushing syndrome due to Sacrococcygeal Teratoma detected by [18F]fluorodeoxyglucose positron emission tomography. J Clin Endocrinol Metab. 2008;93(9):3282–3.

    Article  PubMed  Google Scholar 

  57. 57.

    Nikolaou A, Thomas D, Kampanellou C, Alexandraki K, Andersson LG, Sundin A, et al. The value of 11C-5-hydroxy-tryptophan (5HTP) positron emission tomography (PET) in neuroendocrine tumour diagnosis and management: experience from one center. J Endocrinol Investig. 2010 doi:10.3275/6936.

  58. 58.

    Orlefors H, Sundin A, Garske U, Juhlin C, Oberg K, Skogseid B, et al. Whole-body (11)C-5-hydroxytryptophan positron emission tomography as a universal imaging technique for neuroendocrine tumors: comparison with somatostatin receptor scintigraphy and computed tomography. J Clin Endocrinol Metab. 2005;90:3392–400.

    CAS  Article  PubMed  Google Scholar 

  59. 59.

    Grossrubatscher E, Vignati F, Dalino P, Possa M, Belloni PA, Vanzulli A, et al. Use of radioguided surgery with [111In]-pentetreotide in the management of an ACTH-secreting bronchial carcinoid causing ectopic Cushing’s syndrome. J Endocrinol Investig. 2005;28:72–8.

    CAS  Google Scholar 

  60. 60.

    Connor TB, Wood C, Lance BK, Orth DN, Williams JB. Multiple recurrent carcinoid tumors that secreted adrenocorticotropin (ACTH) over a period of 26 years. The Endocrinologist. 1994;4:177–83.

    Article  Google Scholar 

  61. 61.

    Zografos GN, Markou A, Ageli C, Kopanakis N, Koutmos S, Kaltsas G, et al. Laparoscopic surgery for adrenal tumors. A retrospective analysis. Hormones (Athens) 2006;5:52–6.

    Google Scholar 

  62. 62.

    Morris D, Grossman A. The medical management of Cushing’s syndrome. Ann N Y Acad Sci. 2002;970:119–33.

    CAS  Article  PubMed  Google Scholar 

  63. 63.

    Biller BM, Grossman AB, Stewart PM, et al. Treatment of adrenocorticotropin-dependent Cushing’s syndrome: a consensus statement. J Clin Endocrinol Metab. 2008;93:2454–62.

    CAS  Article  PubMed  Google Scholar 

  64. 64.

    Vassilopoulou-Sellin R. Paraneoplastic hypercortisolism as a risk factor for severe infections in patients with malignant diseases. J Clin Endocrinol Metab. 2001;86:947–8.

    CAS  Article  PubMed  Google Scholar 

  65. 65.

    Drake WM, Perry LA, Hinds CJ, Lowe DG, Reznek RH, Besser GM. Emergency and prolonged use of intravenous etomidate to control hypercortisolemia in a patient with Cushing’s syndrome and peritonitis. J Clin Endocrinol Metab. 1998;83:3542–4.

    CAS  Article  PubMed  Google Scholar 

  66. 66.

    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;86:4104–8.

    CAS  Article  PubMed  Google Scholar 

  67. 67.

    de Bruin C, Feelders RA, Lamberts SW, Hofland LJ. Somatostatin and dopamine receptors as targets for medical treatment of Cushing’s Syndrome. Rev Endocr Metab Disord. 2009;10:91–102.

    CAS  Article  PubMed  Google Scholar 

  68. 68.

    Peri A, Bemporad D, Parenti G, Luciani P, Serio M, Mannelli M. Cushing’s syndrome due to intermittent ectopic ACTH production showing a temporary remission during a pulmonary infection. Eur J Endocrinol. 2001;145:605–11.

    CAS  Article  PubMed  Google Scholar 

  69. 69.

    de Herder WW, Krenning EP, Malchoff CD, Hofland LJ, Reubi JC, Kwekkeboom DJ, et al. Somatostatin receptor scintigraphy: its value in tumor localization in patients with Cushing’s syndrome caused by ectopic corticotropin or corticotropin-releasing hormone secretion. Am J Med. 1994;96:305–12.

    Article  PubMed  Google Scholar 

  70. 70.

    Phlipponneau M, Nocaudie M, Epelbaum J, De Keyzer Y, Lalau JD, Marchandise X, et al. Somatostatin analogs for the localization and preoperative treatment of an adrenocorticotropin-secreting bronchial carcinoid tumor. J Clin Endocrinol Metab. 1994;78:20–4.

    CAS  Article  PubMed  Google Scholar 

  71. 71.

    Bertagna X, Favrod-Coune C, Escourolle H, Beuzeboc P, Christoforov B, Girard F, et al. Suppression of ectopic adrenocorticotropin secretion by the long-acting somatostatin analog octreotide. J Clin Endocrinol Metab. 1989;68:988–91.

    CAS  Article  PubMed  Google Scholar 

  72. 72.

    Vignati F, Loli P. Additive effect of ketoconazole and octreotide in the treatment of severe adrenocorticotropin-dependent hypercortisolism. J Clin Endocrinol Metab. 1996;81:2885–90.

    CAS  Article  PubMed  Google Scholar 

  73. 73.

    Pivonello R, Ferone D, de Herder WW, Faggiano A, Bodei L, de Krijger RR, et al. Dopamine receptor expression and function in corticotroph ectopic tumors. J Clin Endocrinol Metab. 2007;92:65–9.

    CAS  Article  PubMed  Google Scholar 

  74. 74.

    Lamberts SW, Tilanus HW, Klooswijk AI, Bruining HA, van der Lely AJ, de Jong FH. Successful treatment with SMS 201-995 of Cushing’s syndrome caused by ectopic adrenocorticotropin secretion from a metastatic gastrin-secreting pancreatic islet cell carcinoma. J Clin Endocrinol Metab. 1988;67:1080–3.

    CAS  Article  PubMed  Google Scholar 

  75. 75.

    Hofland LJ, Lamberts SW. The pathophysiological consequences of somatostatin receptor internalization and resistance. Endocr Rev. 2003;24:28–47.

    CAS  Article  PubMed  Google Scholar 

  76. 76.

    Pivonello R, Ferone D, Lamberts SW, Colao A. Cabergoline plus lanreotide for ectopic Cushing’s syndrome. N Engl J Med. 2005;352:2457–8.

    CAS  Article  PubMed  Google Scholar 

  77. 77.

    Mansi L, Rambaldi PF, Panza N, Esposito D, Esposito V, Pastore V. Diagnosis and radioguided surgery with 111In-pentetreotide in a patient with paraneoplastic Cushing’s syndrome due to a bronchial carcinoid. Eur J Endocrinol. 1997;137:688–90.

    CAS  Article  PubMed  Google Scholar 

  78. 78.

    Findling JW, Tyrrell JB. Occult ectopic secretion of corticotropin. Arch Intern Med. 1986;146:929–33.

    CAS  Article  PubMed  Google Scholar 

  79. 79.

    Krikorian A, Aron D. Evaluation and management of pituitary incidentalomas-revisiting an acquaintance. Nat Clin Pract Endocrinol Metab. 2006;2:138–45.

    CAS  Article  PubMed  Google Scholar 

  80. 80.

    Vilar L, Freitas MC, Moura E, Campos R, Leal E, Teixeira L, et al. Cushing’s disease caused by macroadenomas—Report of 7 cases. Arq Bras Endocrinol Metabol. 1996;40:S221.

    Google Scholar 

  81. 81.

    Woo YS, Isidori AM, Wat WZ, Kaltsas GA, Afshar F, Sabin I, et al. Clinical and biochemical characteristics of adrenocorticotropin-secreting macroadenomas. J Clin Endocrinol Metab. 2005;90:4963–9.

    CAS  Article  PubMed  Google Scholar 

  82. 82.

    Zerikly RK, Eray E, Faiman C, Prayson R, Lorenz RR, Weil RJ, et al. Cyclic Cushing syndrome due to an ectopic pituitary adenoma. Nat Clin Pract Endocrinol Metab. 2009;5:174–9.

    Article  PubMed  Google Scholar 

  83. 83.

    Meinardi JR, Wolffenbuttel BH, Dullaart RP. Cyclic Cushing’s syndrome: a clinical challenge. Eur J Endocrinol. 2007;157(3):245–54.

    CAS  Article  PubMed  Google Scholar 

  84. 84.

    Albiger NM, Scaroni CM, Mantero F. Cyclic Cushing’s syndrome: an overview. Arq Bras Endocrinol Metabol. 2007;51:1253–60.

    PubMed  Google Scholar 

  85. 85.

    Alexandraki KI, Kaltsas GA, Isidori AM, Akker SA, Drake WM, Chew SL, et al. The prevalence and characteristic features of cyclicity and variability in Cushing’s disease. Eur J Endocrinol. 2009;160:1011–8.

    CAS  Article  PubMed  Google Scholar 

  86. 86.

    Chrisoulidou A, Pazaitou-Panayiotou K, Georgiou E, Boudina M, Kontogeorgos G, Iakovou I, et al. Ectopic Cushing’s syndrome due to CRH secreting liver metastasis in a patient with medullary thyroid carcinoma. Hormones (Athens) 2008;7:259–62.

    Google Scholar 

  87. 87.

    Orth DN. Cushing’s syndrome. N Engl J Med. 1995;332:791–803.

    CAS  Article  PubMed  Google Scholar 

  88. 88.

    Chetty R, Serra S. Spindle cell pancreatic endocrine tumor associated with Cushing’s syndrome. Endocr Pathol. 2005;16:145–51.

    Article  PubMed  Google Scholar 

  89. 89.

    Shah NA, Urusova IA, D’Agnolo A, Colquhoun SD, Rosenbloom BE, Vener SL, et al. Primary hepatic carcinoid tumor presenting as Cushing’s syndrome. J Endocrinol Investig. 2007;30:327–33.

    CAS  Google Scholar 

Download references

Author information

Affiliations

Authors

Corresponding author

Correspondence to Ashley B. Grossman.

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Alexandraki, K.I., Grossman, A.B. The ectopic ACTH syndrome. Rev Endocr Metab Disord 11, 117–126 (2010). https://doi.org/10.1007/s11154-010-9139-z

Download citation

Keywords

  • Ectopic Cushing’s syndrome
  • ACTH ectopic syndrome
  • Cushing’s syndrome
  • Neuroendocrine tumours
  • Carcinoids
  • Small cell lung carcinoma
  • Hypercortisolaemia