, Volume 42, Issue 1, pp 69–73 | Cite as

Mini-review: pheochromocytomas causing the ectopic ACTH syndrome

  • Chitrabhanu Ballav
  • Auditi Naziat
  • Radu Mihai
  • Niki Karavitaki
  • Olaf Ansorge
  • Ashley B. GrossmanEmail author
Mini Review


Cushing’s syndrome (CS) is a condition associated with high cortisol levels and affects around 0.7–2.4 cases per million population per year [1, 2, 3]. Approximately 80 % of cases of CS are secondary to excess adrenocorticotrophin (ACTH) secretion, while in around 20 % the primary abnormality lies in the adrenal, most often an adrenal adenoma or carcinoma. Of the ACTH-dependent causes, some 80–90 % are due to a pituitary adenoma—Cushing’s disease—but in a significant proportion the cause is ectopic secretion from a non-pituitary source, the ectopic ACTH syndrome (EAS) [4]. The commonest source of ACTH secretion in these patients is a bronchial carcinoid. However, many other tumors are capable of secreting ACTH, and in most series a small but significant number are secondary to an ACTH-secreting pheochromocytoma. Amalgamating the data from 6 large series of patients with ectopic ACTH, pheochromocytoma was the source of ACTH secretion in 19 out of 363 patients (5.2 %) [5, 6, 7, 8, 9, 10, 11]. In this mini-review, we present a patient presenting to our department with a pheochromocytoma as well as Cushing’s syndrome due to ectopic ACTH secretion by the pheochromocytoma, and we discuss published cases in the world literature to assess its significance. We emphasize the problems in the simultaneous management of these two serious endocrine conditions.


Pheochromocytoma Cushing’s syndrome ACTH Review 



We are grateful to Dr J Foote and Dr T Dugal, Royal Cornwall Hospital, Truro, UK, for referring this patient.


  1. 1.
    J. Lindholm, S. Juul, J.O. Jorgensen et al., Incidence and late prognosis of Cushing’s syndrome: a population-based study. J. Clin. Endocrinol. Metab. 86, 117–123 (2001)PubMedCrossRefGoogle Scholar
  2. 2.
    J. Etxabe, J.A. Vazquez, Morbidity and mortality in Cushing’s disease: an epidemiological approach. Clin. Endocrinol. (Oxf) 40, 479–484 (1994)CrossRefGoogle Scholar
  3. 3.
    B. Ambrosi, D. Bochicchio, R. Ferrario, P. Colombo, G. Faglia, Screening tests for Cushing’s syndrome. Clin. Endocrinol. (Oxf) 33, 809–811 (1990)CrossRefGoogle Scholar
  4. 4.
    J. Newell-Price, X. Bertagna, A.B. Grossman, L.K. Nieman, Cushing’s syndrome. Lancet 367(9522), 1605–1617 (2006)PubMedCrossRefGoogle Scholar
  5. 5.
    A.M. Isidori, G.A. Kaltsas, C. Pozza, V. Frajese, J. Newell-Price, R.H. Reznek, P.J. Jenkins, J.P. Monson, A.B. Grossman, M. Besser, The ectopic adrenocorticotropin syndrome: clinical features, diagnosis, management and long-term follow-up. J. Clin. Endocrinol. Metab. 91(2), 371–377 (2006)PubMedCrossRefGoogle Scholar
  6. 6.
    I. Ilias, D.J. Torpy, K. Pacak, N. Mullen, R.A. Wesley, L.K. Nieman, Cushing’s syndrome due to ectopic corticotropin secretion: 20 years’ experience at the National Institute of Health. J. Clin. Endocrinol. Metab. 90(8), 4955–4962 (2005)PubMedCrossRefGoogle Scholar
  7. 7.
    J.P. Aniszweski, W.F. Young, G.B. Thompson, C.S. Grant, J.A. Heerden, Cushing syndrome due to ectopic adrenocorticotropic hormone secretion. World J. Surg. 25(7), 934–940 (2001)CrossRefGoogle Scholar
  8. 8.
    D.J. Torpy, N. Mullen, I. Ilias, L.K. Nieman, Association of hypertension and hypokalemia with Cushing’s syndrome caused by ectopic ACTH secretion a series of 58 cases. Ann. N Y Acad. Sci. 970, 134–144 (2002)PubMedCrossRefGoogle Scholar
  9. 9.
    J.L. Doppman, L. Nieman, D.L. Miller, H.I. Pass, R. Chang, G.B. Cutler, M. Scaaf, G.P. Chrousos, J.A. Norton, H.A. Ziessman, Ectopic adrenocorticotropic hormone syndrome: localization studies in 28 patients. Radiology 172, 115–124 (1989)PubMedGoogle Scholar
  10. 10.
    T.A. Howlett, P.L. Drury, L. Perry, I. Doniach, L.H. Rees, G.M. Besser, Diagnosis and management of ACTH-dependent Cushing’s syndrome: comparison of the features in ectopic and pituitary ACTH production. Clin. Endocrinol. 24(6), 699–713 (1986)CrossRefGoogle Scholar
  11. 11.
    L.R. Salgado, M.C.B. Fragoso, M. Knoepfelmacher, M.C. Machado, M. Domenice, A. Pereira, B.B. de Mendonca, Ectopic ACTH syndrome: our experience with 25 cases. Eur. J. Endocrinol. 155, 725–733 (2006)PubMedCrossRefGoogle Scholar
  12. 12.
    B.H. Forman, E. Marban, R. Kayne, N.M. Passarelli, S.N. Bobrow, V.A. Livolsi, M. Merino, M. Minor, L.R. Farber, Ectopic ACTH syndrome due to pheochromocytoma: case report and review of literature. Yale J. Biol. Med. 52, 181–189 (1979)PubMedGoogle Scholar
  13. 13.
    H. Chen, J.L. Doppman, G.P. Chrousos, J.A. Norton, L.K. Nieman, R. Udelsman, Adrenocorticotropic hormone-secreting pheochromocytomas: The exception to the rule. Surgery 118, 988–995 (1995)PubMedCrossRefGoogle Scholar
  14. 14.
    J. Bourgoignie, J.C.I. Dupont, R. Noiret, Association d’un pheochromocytome et d’un hypercorticisme du type Cushing avec hyperaldosteronurie. Ann. Endocrinol. (Paris) 25, 269 (1964)Google Scholar
  15. 15.
    M.F. Nijhoff, O.M. Dekkers, L.J. Vleming, J.W.A. Smit, J.A. Romijn, A.M. Pereira, ACTH-producing pheochromocytoma: clinical considerations and concise review of literature. Eur. J. Intern. Med. 20, 682–685 (2009)PubMedCrossRefGoogle Scholar
  16. 16.
    K.C. Loh, R. Gupta, A.H. Shlossberg, Spontaneous remission of ectopic Cushing’s syndrome due to pheochromocytoma: a case report. Eur. J. Endocrinol. 135(4), 440–443 (1996)PubMedCrossRefGoogle Scholar
  17. 17.
    H.C. Oh, J.M. Koh, M.S. Kim, J.Y. Park, Y.K. Shong, K.U. Lee, J.S. Kim, J.S. Hong, H.L. Koo, W.B. Kim, A case of ACTH-producing pheochromocytoma associated with pregnancy. Endocr. J. 50(6), 739–744 (2003)PubMedCrossRefGoogle Scholar
  18. 18.
    M. Quinkler, P.M. Stewart, Hypertension and the cortisol–cortisone shuttle. J. Clin. Endocrinol. Metab. 88, 2384–2392 (2003)PubMedCrossRefGoogle Scholar
  19. 19.
    E. Resmini, F. Minuto, A. Colao, D. Ferone, Secondary diabetes associated with principal endocrinopathies: the impact of new treatment modalities. Acta Diabetol. 46(2), 85–95 (2009)PubMedCrossRefGoogle Scholar
  20. 20.
    G. Mazziotti, C. Gazzaruso, A. Giustina, Diabetes in Cushing syndrome: basic and clinical aspects. Trends Endocrinol. Metab. 22(12), 499–506 (2011)PubMedCrossRefGoogle Scholar
  21. 21.
    L.K. Nieman, B.M.K. Biller, J.W. Findling, J. Newell-Price, M.O. Savage, P.M. Stewart, V.M. Montori, The diagnosis of Cushing’s syndrome: an endocrine society clinical practice guideline. J. Clin. Endocrinol. Metab. 93(5), 1526–1540 (2008)PubMedCrossRefGoogle Scholar
  22. 22.
    M. Terzolo, A. Alì, A. Pia, E. Bollito, G. Reimondo, P. Paccotti, R. Scardapane, A. Angeli, Cyclic Cushing’s syndrome due to ectopic ACTH secretion by an adrenal pheochromocytoma. J. Endocrinol. Invest. 17(11), 869–874 (1994)PubMedGoogle Scholar
  23. 23.
    L. Crapo, Cushing’s syndrome: a review of diagnostic tests. Metabolism 28, 955–977 (1979)PubMedCrossRefGoogle Scholar
  24. 24.
    J. Newell-Price, P. Trainer, M. Besser, A. Grossman, The diagnosis and differential diagnosis of Cushing’s syndrome and pseudo-Cushing’s states. Endocr. Rev. 19, 647–672 (1998)PubMedCrossRefGoogle Scholar
  25. 25.
    B.B. Mendonça, I.J. Arnhold, W. Nicolau, V.A. Avancini, W. Boise, Cushing’s syndrome due to ectopic ACTH secretion by bilateral pheochromocytomas in multiple endocrine neoplasia type 2A. N. Engl. J. Med. 319(24), 1610–1611 (1988)PubMedGoogle Scholar
  26. 26.
    R. Darr, G. Eisenhofer, J. Kotzerke, K. Zophel, C. Stroszczynski, J. Deinum, L.J.S. Kool, S. Pistorius, H. Neumann, H.R. Bornstein, L.C. Hofbauer, Is there still a place for adrenal venous sampling in the diagnostic localization of pheochromocytoma? Endocrine 40, 75–79 (2011)PubMedCrossRefGoogle Scholar
  27. 27.
    K. Kakudo, K. Uematsu, Y. Matsuno, M. Mitsunobu, A. Toyosaka, E. Okamoto, M. Fukuchi, Malignant pheochromocytoma with ACTH production. Acta Pathol. Jpn. 34(6), 1403–1410 (1984)PubMedGoogle Scholar
  28. 28.
    T.I.M. Korevaar, A.B. Grossman, Pheochromocytomas and paragangliomas: assessment of malignant potential. Endocrine 40, 354–365 (2011)PubMedCrossRefGoogle Scholar
  29. 29.
    M.R. Berenyi, G. Singh, E.S. Gloster, M.I. Davidson, D.H. Woldenberg, ACTH-producing pheochromocytoma. Arch. Pathol. Lab. Med. 101(1), 31–35 (1977)PubMedGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2012

Authors and Affiliations

  • Chitrabhanu Ballav
    • 1
  • Auditi Naziat
    • 1
  • Radu Mihai
    • 2
  • Niki Karavitaki
    • 1
  • Olaf Ansorge
    • 3
  • Ashley B. Grossman
    • 1
    Email author
  1. 1.Oxford Centre for Diabetes, Endocrinology and MetabolismChurchill Hospital, University of OxfordOxfordUK
  2. 2.Department of SurgeryOxford University Hospitals, University of OxfordOxfordUK
  3. 3.Department of PathologyOxford University Hospitals, University of OxfordOxfordUK

Personalised recommendations