Exp Clin Endocrinol Diabetes 2011; 119(09): 525-529
DOI: 10.1055/s-0031-1284368
Case Report
© J. A. Barth Verlag in George Thieme Verlag KG Stuttgart · New York

Ectopic ACTH-syndrome due to a Neuroendocrine Tumour of the Appendix

N. Perakakis
1   Division of Endocrinology and Diabetology, Department of Internal Medicine II, University Hospital of Freiburg
,
K. Laubner
1   Division of Endocrinology and Diabetology, Department of Internal Medicine II, University Hospital of Freiburg
,
T. Keck
2   Department of General and Visceral Surgery, University Hospital of Freiburg
,
D. Steffl
3   Department of Nephrology, University Hospital of Freiburg
,
M. Lausch
3   Department of Nephrology, University Hospital of Freiburg
,
P. T. Meyer
4   Department of Nuclear Medicine, University Hospital of Freiburg
,
D. Burger
5   Department of Diagnostic Radiology, University Hospital of Freiburg
,
A. Csanadi
6   Institute of Pathology, University Hospital of Freiburg
,
J. Seufert
1   Division of Endocrinology and Diabetology, Department of Internal Medicine II, University Hospital of Freiburg
› Author Affiliations
Further Information

Publication History

received 16 May 2011
firstdecision 29 June 2011

accepted 12 July 2011

Publication Date:
17 October 2011 (online)

Abstract

Ectopic ACTH production causes 10% of Cushing’s syndromes. The diagnostic workup is difficult, can last more than 6 months (> 50% of cases), and the underlying tumour is still frequently not located (12%). Carcinoid tumours of the appendix are frequent and are revealed in 0.3% of patients undergoing routine appendectomy. However, neuroendocrine tumours of the appendix with ACTH production are an extremely rare entity.

Here we report the case of a female patient with clinically overt Cushing’s syndrome due to ectopic ACTH-production from a carcinoid tumour of the appendix. During the diagnostic workup, repeated endocrine tests, multiple different imaging modalities and frequent and lengthy hospitalisations were necessary. Wrongly, even a neurosurgical pituitary exploration was performed. After 12 months from the initial admission, the tumour was finally detected by an 18F-fluoro-L-dihydroxyphenylalanine (18FDOPA PET) and an appendectomy followed by right hemicolectomy were performed. The patient recovered rapidly and the symptoms from the hypercortisolism were no more present.

In this case, we discuss the multitude of problems, which may delay the diagnosis and the pitfalls, that should be avoided in order to locate the tumour and to initiate adequate therapy as early as possible. Furthermore, our case demonstrates the complexity of diagnostic procedures, which demand most of the times a multidisciplinary approach. In this setting, regular follow-ups in short time intervals and the use of novel imaging techniques can finally cut the diagnostic “Gordian knot”.

 
  • References

  • 1 Adams S, Baum RP, Stuckensen T et al. 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: 1255-1260
  • 2 Aniszewski JP, Young Jr WF, Thompson GB et al. Cushing syndrome due to ectopic adrenocorticotropic hormone secretion. World J Surg 2001; 25: 934-940
  • 3 Beuschlein F, Hammer GD. Ectopic pro-opiomelanocortin syndrome. Endocrinol Metab Clin North Am 2002; 31: 191-234
  • 4 Boscaro M, Arnaldi G. Approach to the patient with possible Cushing’s syndrome. J Clin Endocrinol Metab 2009; 94: 3121-3131
  • 5 Boudreaux JP, Klimstra DS, Hassan MM et al. The NANETS consensus guideline for the diagnosis and management of neuroendocrine tumors: well-differentiated neuroendocrine tumors of the Jejunum, Ileum, Appendix, and Cecum. Pancreas 2010; 39: 753-766
  • 6 Delisle L, Boyer MJ, Warr D. Ectopic corticotropin syndrome and small-cell carcinoma of the lung. Clinical features, outcome, and complications. Arch Intern Med 1993; 153: 746-752
  • 7 Deschamps L, Couvelard A. Endocrine tumors of the appendix: a pathologic review. Arch Pathol Lab Med 2010; 134: 871-875
  • 8 Doppman JL, Nieman L, Miller DL et al. Ectopic adrenocorticotropic hormone syndrome: localization studies in 28 patients. Radiology 1989; 172: 115-124
  • 9 Howlett TA, Drury PL, Perry L et al. 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
  • 10 Ilias I, Torpy DJ, Pacak K et al. 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
  • 11 Invitti C, Pecori Giraldi F, de Martin M et al. 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-Pituitary-Adrenal Axis. J Clin Endocrinol Metab 1999; 84: 440-448
  • 12 Isidori AM, Kaltsas GA, Grossman AB. Ectopic ACTH syndrome. Front Horm Res 2006a 35: 143-156
  • 13 Isidori AM, Kaltsas GA, Pozza C et al. The ectopic adrenocorticotropin syndrome: clinical features, diagnosis, management, and long-term follow-up. J Clin Endocrinol Metab 2006b 91: 371-377
  • 14 Isidori AM, Lenzi A. Ectopic ACTH syndrome. Arq Bras Endocrinol Metabol 2007; 51: 1217-1225
  • 15 Kaltsas GA, Giannulis MG, Newell-Price JD 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: 487-492
  • 16 Kaye TB, Crapo L. The Cushing syndrome: an update on diagnostic tests. Ann Intern Med 1990; 112: 434-444
  • 17 Kumar J, Spring M, Carroll PV et al. 18Flurodeoxyglucose positron emission tomography in the localization of ectopic ACTH-secreting neuroendocrine tumours. Clin Endocrinol (Oxf) 2006; 64: 371-374
  • 18 Lindsay JR, Nieman LK. Differential diagnosis and imaging in Cushing’s syndrome. Endocrinol Metab Clin North Am 2005; 34: 403-421 x
  • 19 Markou A, Manning P, Kaya B et al. [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: 521-525
  • 20 Meier CA, Biller BM. Clinical and biochemical evaluation of Cushing’s syndrome. Endocrinol Metab Clin North Am 1997; 26: 741-762
  • 21 Moreno-Fernandez J, Gutierrez-Alcantara C, Galvez Moreno MA et al. Corticotrophin-dependent Cushing syndrome due to Sacrococcygeal Teratoma detected by [18F]fluorodeoxyglucose positron emission tomography. J Clin Endocrinol Metab 2008; 93: 3282-3283
  • 22 Mullen JT, Savarese DM. Carcinoid tumors of the appendix: A population-based study. J Surg Oncol 2011; 104: 41-44
  • 23 Newell-Price J, Morris DG, Drake WM 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: 1640-1645
  • 24 Newell-Price J, Trainer P, Besser M et al. The diagnosis and differential diagnosis of Cushing’s syndrome and pseudo-Cushing’s states. Endocr Rev 1998; 19: 647-672
  • 25 Nieman LK, Oldfield EH, Wesley R et al. 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: 1308-1312
  • 26 Oldfield EH, Doppman JL, Nieman LK 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
  • 27 Pacak K, Ilias I, Chen CC et al. 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: 2214-2221
  • 28 Putzer D, Gabriel M, Kendler D. et al. Comparison of (68)Ga-DOTA-Tyr(3)-octreotide and (18)F-fluoro-L-dihydroxyphenylalanine positron emission tomography in neuroendocrine tumor patients. Q J Nucl Med Mol Imaging 2010; 54: 68-75
  • 29 Salgado LR, Fragoso MC, Knoepfelmacher M et al. Ectopic ACTH syndrome: our experience with 25 cases. Eur J Endocrinol 2006; 155: 725-733
  • 30 Shrager JB, Wright CD, Wain JC et al. Bronchopulmonary carcinoid tumors associated with Cushing’s syndrome: a more aggressive variant of typical carcinoid. J Thorac Cardiovasc Surg 1997; 114: 367-375
  • 31 Tabarin A, Valli N, Chanson P et al. Usefulness of somatostatin receptor scintigraphy in patients with occult ectopic adrenocorticotropin syndrome. J Clin Endocrinol Metab 1999; 84: 1193-1202
  • 32 Vilar L, Freitas Mda C, Faria M et al. Pitfalls in the diagnosis of Cushing’s syndrome. Arq Bras Endocrinol Metabol 2007; 51: 1207-1216
  • 33 Vilar L, Naves LA, Freitas Mda C et al. Endogenous Cushing’s syndrome: clinical and laboratorial features in 73 cases. Arq Bras Endocrinol Metabol 2007; 51: 566-574
  • 34 Wajchenberg BL, Mendonca BB, Liberman B et al. Ectopic adrenocorticotropic hormone syndrome. Endocr Rev 1994; 15: 752-787
  • 35 Zemskova MS, Gundabolu B, Sinaii N et al. Utility of Various functional and Anatomic Imaging Modalities for Detection of Ectopic Adrenocorticotropin-Secreting Tumors. J Clin Endocrinol Metab 2010; 95: 1207-1219