Reviews in Endocrine and Metabolic Disorders

, Volume 11, Issue 2, pp 117–126

The ectopic ACTH syndrome

  • Krystallenia I. Alexandraki
  • Ashley B. Grossman

DOI: 10.1007/s11154-010-9139-z

Cite this article as:
Alexandraki, K.I. & Grossman, A.B. Rev Endocr Metab Disord (2010) 11: 117. doi:10.1007/s11154-010-9139-z


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.


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



Bilateral inferior petrosal sinus sampling


Corticotropin-releasing hormone


ACTH ectopic syndrome


[18F]Flurodeoxyglucose positron emission tomography


High-dose dexamethasone test


Low-dose dexamethasone test


Medullary carcinoma of the thyroid


Neuroendocrine tumours


Neuron-specific enolase


111In-octreotide scintigraphy




Small cell lung carcinoma


Somatostatin analogues

Copyright information

© Springer Science+Business Media, LLC 2010

Authors and Affiliations

  • Krystallenia I. Alexandraki
    • 1
  • Ashley B. Grossman
    • 1
  1. 1.Department of EndocrinologySt. Bartholomew’s HospitalLondonUK

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