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Imaging Strategies for Localization of ACTH-Secreting Tumors

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The Hypothalamic-Pituitary-Adrenal Axis in Health and Disease

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Abstract

The causes of ACTH-dependent Cushing’s syndrome include corticotrope tumors that secrete ACTH (Cushing’s disease) and tumors outside the pituitary gland that secrete ACTH “ectopically” (Ectopic ACTH secretion). Since pituitary tumors are much more common, imaging usually begins with a pituitary MRI. The specific protocol used for the study influences the ability to identify a tumor, but even the best protocols do not identify more than 80 % of these tumors.

Ectopic ACTH-secreting tumors occur most commonly in the thorax but may be found in the neck, abdomen, or pelvis. Structural imaging with CT (and MRI as an adjunctive modality) is the mainstay but is complemented by function imaging, usually with somatostatin analogs. Since many tumors are occult at initial presentation, imaging is repeated at intervals until a tumor is identified and (hopefully) resected.

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References

  1. Atlas SW. Magnetic resonance imaging of the brain and spine. 3rd ed. Baltimore: Lippincott Williams & Wilkins; 2002.

    Google Scholar 

  2. Rajan SS. MRI: a conceptual overview. New York: Springer; 1998.

    Book  Google Scholar 

  3. Doppman JL, Frank JA, Dwyer AJ, Oldfield EH, Miller DL, Nieman LK, Chrousos GP, Cutler Jr GB, Loriaux DL. Gadolinium DTPA enhanced MR imaging of ACTH-secreting microadenomas of the pituitary gland. J Comput Assist Tomogr. 1988;12:728–35.

    Article  CAS  PubMed  Google Scholar 

  4. Dwyer AJ, Frank JA, Doppman JL, Oldfield EH, Hickey AM, Cutler GB, Loriaux DL, Schiable TF. Pituitary adenomas in patients with Cushing disease: initial experience with Gd-DTPA-enhanced MR imaging. Radiology. 1987;163:421–6.

    Article  CAS  PubMed  Google Scholar 

  5. Peck WW, Dillon WP, Norman D, Newton TH, Wilson CB. High resolution MR imaging of pituitary microadenomas at 1.5 T: experience with Cushing disease. AJR Am J Roentgenol. 1989;152:145–51.

    Article  CAS  PubMed  Google Scholar 

  6. Patronas N, Bulakbasi N, Stratakis C, Lafferty A, Oldfield EH, Doppman J, Nieman LK. Spoiled gradient recalled acquisition in the steady state technique is superior to conventional postcontrast spin echo technique for magnetic resonance imaging detection of adrenocorticotropin-secreting pituitary tumors. J Clin Endocrinol Metab. 2003;88:1665–9.

    Article  Google Scholar 

  7. Stadnik T, Stevenaert A, Beckers A, Luypaert R, Buisseret T, Osteaux M. Pituitary microadenomas: diagnosis with two-and three-dimensional MR imaging at 1.5 T before and after injection of gadolinium. Radiology. 1990;176:419–28.

    Article  CAS  PubMed  Google Scholar 

  8. Tabarin A, Laurent F, Catargi B, Olivier-Puel F, Lescene R, Berge J, Galli FS, Drouillard J, Roger P, Guerin J. Comparative evaluation of conventional and dynamic magnetic resonance imaging of the pituitary gland for the diagnosis of Cushing’s disease. Clin Endocrinol (Oxf). 1998;49:293–300.

    Article  CAS  Google Scholar 

  9. Kasaliwal R, Sankhe SS, Lila AR, Budyal SR, Jagtap VS, Sarathi V, Kakade H, Bandgar T, Menon PS, Shah NS. Volume interpolated 3D-spoiled gradient echo sequence is better than dynamic contrast spin echo sequence for MRI detection of corticotropin secreting pituitary microadenomas. Clin Endocrinol (Oxf). 2013;78:825–30.

    Article  CAS  Google Scholar 

  10. Erickson D, Erickson B, Watson R, Patton A, Atkinson J, Meyer F, Nippoldt T, Carpenter P, Natt N, Vella A, Thapa P. 3 Tesla magnetic resonance imaging with and without corticotropin releasing hormone stimulation for the detection of microadenomas in Cushing’s syndrome. Clin Endocrinol (Oxf). 2010;72:793–9.

    Article  CAS  Google Scholar 

  11. Stobo DB, Lindsay RS, Connell JM, Dunn L, Forbes KP. Initial experience of 3 Tesla versus conventional field strength magnetic resonance imaging of small functioning pituitary tumours. Clin Endocrinol (Oxf). 2011;75:673–7.

    Article  Google Scholar 

  12. Hall WA, Luciano MG, Doppman JL, Patronas NJ, Oldfield EH. Pituitary magnetic resonance imaging in normal human volunteers: occult adenomas in the general population. Ann Intern Med. 1994;120:817–20.

    Article  CAS  PubMed  Google Scholar 

  13. Wind JJ, Lonser RR, Nieman LK, DeVroom HL, Chang R, Oldfield EH. The lateralization accuracy of inferior petrosal sinus sampling in 501 patients with Cushing’s disease. J Clin Endocrinol Metab. 2013;98:2285–93.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. 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.

    Article  CAS  PubMed  Google Scholar 

  15. Yogi-Morren D, Habra MA, Faiman C, Bena J, Hatipoglu B, Kennedy L, Weil RJ, Hamrahian AH. Pituitary MRI findings in patients with pituitary and ectopic ACTH-dependent Cushing syndrome: does a 6-mm pituitary tumor size Cut-Off value exclude ectopic ACTH syndrome? Endocr Pract. 2015;21:1098–103.

    Article  PubMed  Google Scholar 

  16. Gurazada K, Ihuoma A, Galloway M, Dorward N, Wilhelm T, Khoo B, Bouloux PM. Nasally located ectopic ACTH-secreting pituitary adenoma (EAPA) causing Nelson’s syndrome: diagnostic challenges. Pituitary. 2014;17:423–9.

    Article  CAS  PubMed  Google Scholar 

  17. Flitsch J, Schmid SM, Bernreuther C, Winterberg B, Ritter MM, Lehnert H, Burkhardt T. A pitfall in diagnosing Cushing’s disease: ectopic ACTH-producing pituitary adenoma in the sphenoid sinus. Pituitary. 2015;18:279–82.

    Article  CAS  PubMed  Google Scholar 

  18. Mason RB, Nieman LK, Doppman JL, Oldfield EH. Selective excision of adenomas originating in or extending into the pituitary stalk with preservation of pituitary function. J Neurosurg. 1997;87:343–51.

    Article  CAS  PubMed  Google Scholar 

  19. Pluta RM, Nieman L, Doppman JL, et al. Extrapituitary parasellar microadenoma in Cushing’s disease. J Clin Endocrinol Metab. 1999;84:2912–23.

    CAS  PubMed  Google Scholar 

  20. Weil RJ, Vortmeyer AO, Nieman LK, Devroom HL, Wanebo J, Oldfield EH. Surgical remission of pituitary adenomas confined to the neurohypophysis in Cushing’s disease. J Clin Endocrinol Metab. 2006;91:2656–64.

    Article  CAS  PubMed  Google Scholar 

  21. Koulouri O, Steuwe A, Gillett D, Hoole AC, Powlson AS, Donnelly NA, Burnet NG, Antoun NM, Cheow H, Mannion RJ, Pickard JD, Gurnell M. A role for 11C-methionine PET imaging in ACTH-dependent Cushing’s syndrome. Eur J Endocrinol. 2015;173:M107–20.

    Article  CAS  PubMed  Google Scholar 

  22. Chittiboina P, Montgomery BK, Millo C, Herscovitch P, Lonser RR. High-resolution(18)F-fluorodeoxyglucose positron emission tomography and magnetic resonance imaging for pituitary adenoma detection in Cushing disease. J Neurosurg. 2015;122:791–7.

    Article  CAS  PubMed  Google Scholar 

  23. Nieman LK, Biller BM, Findling JW, Murad MH, Newell-Price J, Savage MO, Tabarin A, Endocrine Society. Treatment of Cushing’s syndrome: an endocrine society clinical practice guideline. J Clin Endocrinol Metab. 2015;100:2807–31.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Isidori AM, Sbardella E, Zatelli MC, Boschetti M, Vitale G, Colao A, Pivonello R, ABC Study Group. Conventional and nuclear medicine imaging in ectopic Cushing’s syndrome: a systematic review. J Clin Endocrinol Metab. 2015;100:3231–44.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Alexandraki KI, Grossman AB. The ectopic ACTH syndrome. Rev Endocr Metab Disord. 2010;11:117–26.

    Article  PubMed  Google Scholar 

  26. Sookur PA, Sahdev A, Rockall AG, Isidori AM, Monson JP, Grossman AB, Reznek RH. Imaging in covert ectopic ACTH secretion: a CT pictorial review. Eur Radiol. 2009;19:1069–78.

    Article  PubMed  Google Scholar 

  27. Tamm EP, Bhosale P, Lee JH, Rohren EM. State-of-the-art imaging of pancreatic neuroendocrine tumors. Surg Oncol Clin N Am. 2016;25:375–400.

    Article  PubMed  Google Scholar 

  28. Papotti M, Croce S, Bello M, Bongiovanni M, Allia E, Schindler M, Bussolati G. Expression of somatostatin receptor types 2, 3 and 5 in biopsies and surgical specimens of human lung tumours. Correlation with preoperative octreotide scintigraphy. Virchows Arch. 2001;439:787–97.

    Article  CAS  PubMed  Google Scholar 

  29. Kwekkeboom DJ, Krenning EP, Bakker WH, Oei HY, Kooij PP, Lamberts SW. Somatostatin analogue scintigraphy in carcinoid tumours. Eur J Nucl Med. 1993;20:283–92.

    Article  CAS  PubMed  Google Scholar 

  30. McCarthy KE, Espenan GD, Cronin M, Anthony LB, Woltering EA. Visualization of somatostatin receptor-positive lesions with 111-In-pentetreotide is dose dependent. Dig Dis Sci. 1998;43:1876.

    Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  32. Tsagarakis S, Christoforaki M, Giannopoulou H, Rondogianni F, Housianakou I, Malagari C, Rontogianni D, Bellenis I, Thalassinos N. 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.

    Article  CAS  PubMed  Google Scholar 

  33. Torpy DJ, Chen CC, Mullen N, Doppman JL, Carrasquillo JA, Chrousos GP, Nieman LK. 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.

    Article  CAS  PubMed  Google Scholar 

  34. Ejaz S, Vassilopoulou-Sellin R, Busaidy NL, Hu MI, Waguespack SG, Jimenez C, Ying AK, Cabanillas M, Abbara M, Habra MA. Cushing syndrome secondary to ectopic adrenocorticotropic hormone secretion: the University of Texas MD Anderson Cancer Center Experience. Cancer. 2011;117:4381–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. Özkan ZG, Kuyumcu S, Balköse D, Ozkan B, Aksakal N, Yılmaz E, Sanlı Y, Türkmen C, Aral F, Adalet I. The value of somatostatin receptor imaging with In-111 Octreotide and/or Ga-68 DOTATATE in localizing ectopic ACTH producing tumors. Mol Imaging Radionucl Ther. 2013;22:49–55.

    Article  PubMed  PubMed Central  Google Scholar 

  36. Zemskova MS, Gundabolu B, Sinaii N, Chen CC, Carrasquillo JA, Whatley M, Chowdhury I, Gharib AM, Nieman LK. Utility of various functional and anatomic imaging modalities for detection of ectopic adrenocorticotropin-secreting tumors. J Clin Endocrinol Metab. 2010;95:1207–19.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. Gabriel M, Decristoforo C, Kendler D, Dobrozemsky G, Heute D, Uprimny C, Kovacs P, Von Guggenberg E, Bale R, Virgolini IJ. 68Ga-DOTA-Tyr3-Octreotide PET in neuroendocrine tumors: comparison with somatostatin receptor scintigraphy and CT. J Nucl Med. 2007;48:508–18.

    Article  CAS  PubMed  Google Scholar 

  38. Koukouraki S, Strauss LG, Georgoulias V, Eisenhut M, Haberkorn U, Dimitrakopoulou-Strauss A. Comparison of the pharmacokinetics of 68Ga-DOTATOC and [18F] FDG in patients with metastatic neuroendocrine tumours scheduled for 90Y-DOTATOC therapy. Eur J Nucl Med Mol Imaging. 2006;33:1115–22.

    Article  CAS  PubMed  Google Scholar 

  39. Kayani I, Conry BG, Groves AM, Win T, Dickson J, Caplin M, Bomanji JB. A comparison of 68Ga-DOTATATE and 18F-FDG PET/CT in pulmonary neuroendocrine tumors. J Nucl Med. 2009;50:1927–32.

    Article  PubMed  Google Scholar 

  40. Jindal T, Kumar A, Venkitaraman B, Dutta R, Kumar R. Role of (68)Ga-DOTATOC PET/CT in the evaluation of primary pulmonary carcinoids. Korean J Intern Med. 2010;25:386–91.

    Article  PubMed  PubMed Central  Google Scholar 

  41. Goroshi M, Jadhav S, Lila AR, Kasaliwal R, Khare S, Yerawar C, Hira P, Phadke U, Shah H, Lele V, Malhotra G, Bandgar TR, Shah N. Comparison of 68Ga-DOTANOC PET/CT and CECT in localisation of tumors in EAS. Endocr Connect. 2016;5(2):83–91.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  42. Conti PS, Lilien DL, Hawley K, Keppler J, Grafton ST, Bading JR. PET and [18F]-FDG in oncology: a clinical update. Nucl Med Biol. 1996;23:717–35.

    Article  CAS  PubMed  Google Scholar 

  43. 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 

  44. Timmers HJ, Kozupa A, Chen CC, Carrasquillo JA, Ling A, Eisenhofer G, Adams KT, Solis D, Lenders JW, Pacak K. Superiority of fluorodeoxyglucose positron emission tomography to other functional imaging techniques in the evaluation of metastatic SDHB associated pheochromocytoma and paraganglioma. J Clin Oncol. 2007;25:2262–9.

    Article  PubMed  Google Scholar 

  45. Pearse AG. The cytochemistry and ultrastructure of polypeptide hormone-producing cells of the APUD series and the embryologic, physiologic and pathologic implications of the concept. J Histochem Cytochem. 1969;17:303–13.

    Article  CAS  PubMed  Google Scholar 

  46. Sundin A, Eriksson B, Bergstrom M, Långström B, Oberg K, Orlefors H. PET in the diagnosis of neuroendocrine tumors. Ann N Y Acad Sci. 2004;1014:246–57.

    Article  CAS  PubMed  Google Scholar 

  47. Bergstrom M, Eriksson B, Oberg K, Sundin A, Ahlström H, Lindner KJ, Bjurling P, Långström B. In vivo demonstration of enzyme activity in endocrine pancreatic tumors: Decarboxylation of carbon-11-DOPA to carbon-11-dopamine. J Nucl Med. 1996;37:32–7.

    CAS  PubMed  Google Scholar 

  48. Gazdar AF, Helman LJ, Israel MA, Russell EK, Linnoila RI, Mulshine JL, Schuller HM, Park JG. Expression of neuroendocrine cell markers L-dopa decarboxylase, chromogranin A, and dense core granules in human tumors of endocrine and nonendocrine origin. Cancer Res. 1988;48:4078–82.

    CAS  PubMed  Google Scholar 

  49. Nikolaou A, Thomas D, Kampanellou C, Alexandraki K, Andersson LG, Sundin A, Kaltsas G. The value of 11C-5-hydroxy-tryptophan positron emission tomography in neuroendocrine tumor diagnosis and management: experience from one center. J Endocrinol Invest. 2010;33:794–9.

    Article  CAS  PubMed  Google Scholar 

  50. de Herder WW, Lamberts SW. Tumor localization: the ectopic ACTH syndrome. J Clin Endocrinol Metab. 1999;84:1184–5.

    PubMed  Google Scholar 

  51. Chowdhury IN, Sinaii N, Oldfield EH, Patronas N, Nieman LK. A change in pituitary magnetic resonance imaging protocol detects ACTH-secreting tumours in patients with previously negative results. Clin Endocrinol (Oxf). 2010;72:502–6.

    Article  Google Scholar 

  52. de Rotte AA, Groenewegen A, Rutgers DR, Witkamp T, Zelissen PM, Meijer FJ, van Lindert EJ, Hermus A, Luijten PR, Hendrikse J. High resolution pituitary gland MRI at 7.0 Tesla: a clinical evaluation in Cushing’s disease. Eur Radiol. 2016;26:271–7.

    Article  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  54. 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.

    Article  CAS  PubMed  Google Scholar 

  55. 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.

    Article  CAS  PubMed  Google Scholar 

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

    CAS  PubMed  Google Scholar 

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

    CAS  PubMed  Google Scholar 

  58. Pinker K, Ba-Ssalamah A, Wolfsberger S, Mlynarik V, Knosp E, Trattnig S. The value of high-field MRI (3T) in the assessment of sellar lesions. Eur J Radiol. 2005;54:327–34.

    Article  CAS  PubMed  Google Scholar 

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Authors and Affiliations

  1. Diabetes, Endocrinology and Obesity Branch, National Institute of Diabetes and Digestive and Kidney Diseases, Bethesda, MD, USA

    Lynnette K. Nieman M.D.

  2. Biomedical and Metabolic Imaging Branch, National Institute of Diabetes and Digestive and Kidney Diseases, Bethesda, MD, USA

    Ahmed M. Gharib M.D.

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  1. Lynnette K. Nieman M.D.
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  2. Ahmed M. Gharib M.D.
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Correspondence to Lynnette K. Nieman M.D. .

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Editors and Affiliations

  1. Division of Endocrinology, Multidisciplinary Pituitary and Skull Base Tumor Center, Memorial Sloan Kettering Cancer Center, New York, New York, USA

    Eliza B. Geer

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Nieman, L.K., Gharib, A.M. (2017). Imaging Strategies for Localization of ACTH-Secreting Tumors. In: Geer, E. (eds) The Hypothalamic-Pituitary-Adrenal Axis in Health and Disease. Springer, Cham. https://doi.org/10.1007/978-3-319-45950-9_7

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  • DOI: https://doi.org/10.1007/978-3-319-45950-9_7

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