Endocrine Pathology

, Volume 24, Issue 1, pp 25–29 | Cite as

Recurrent Acute-Onset Cushing’s Syndrome 6 Years after Removal of a Thymic Neuroendocrine Carcinoma: From Ectopic ACTH to CRH

  • Camilla Schalin-JänttiEmail author
  • Sylvia L. Asa
  • Johanna Arola
  • Timo Sane


We describe a rare case of ectopic Cushing’s syndrome that recurred 6 years after resection of a thymic neuroendocrine carcinoma. We discuss reasons for the differing clinical presentations, management, hormone profiles, as well as immunopathology. A 41-year-old male developed acute-onset Cushing’s syndrome. Clinical presentation and laboratory results were compatible with ectopic adrenocorticotropin hormone (ACTH) production. Computerized tomography (CT) showed a 3.6 cm thymic tumor which was successfully resected. Plasma ACTH (P-ACTH) normalized the first postoperative day. Histopathology demonstrated a well-differentiated neuroendocrine carcinoma with diffuse positivity for ACTH and focal corticotropin-releasing hormone (CRH) reactivity in a few scattered cells. The patient was in remission for 6 years. He then again presented with acute-onset Cushing’s syndrome. Fluorine-labeled dihydroxyphenylalanine (18F-DOPA) PET/CT showed local uptake in the mediastinum and he underwent repeat resection. However, P-ACTH remained increased (613 ng/l) and 24-h urinary cortisol was 36,720 nmol, suggesting incomplete tumor removal or metastatic spread. Metyrapone treatment was initiated but then withdrawn because the patient spontaneously recovered and cortisol metabolism gradually normalized within 3 weeks. Histopathology demonstrated a recurrent neuroendocrine carcinoma with the same features as the previous lesion but this time CRH was strongly positive in more numerous cells. Normalization of P-ACTH after primary surgery was compatible with ectopic ACTH production. However, the delayed fall in P-ACTH and serum cortisol is compatible with ectopic CRH production and stimulation of pituitary ACTH secretion, which gradually resolved. Although ectopic CRH production is very rare, the unusual dynamics illustrated here should raise the possibility of CRH production by a neuroendocrine tumor.


Cushing’s syndrome Neuroendocrine carcinoma Ectopic ACTH Ectopic CRH Immunostaining 



We thank Dr. Marko Seppänen at the Turku PET Centre, Turku University Hospital, Turku, Finland for providing the 18F-DOPA PET/CT images.


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Copyright information

© Springer Science+Business Media New York 2012

Authors and Affiliations

  • Camilla Schalin-Jäntti
    • 1
    • 2
    Email author
  • Sylvia L. Asa
    • 5
  • Johanna Arola
    • 3
    • 4
  • Timo Sane
    • 1
  1. 1.Division of Endocrinology, Department of MedicineHelsinki University Central HospitalHelsinkiFinland
  2. 2.University of HelsinkiHelsinkiFinland
  3. 3.Department of Pathology, Haartman InstituteUniversity of HelsinkiHelsinkiFinland
  4. 4.HUSLABHelsinki University HospitalHelsinkiFinland
  5. 5.Department of Laboratory Medicine and PathobiologyUniversity of TorontoTorontoCanada

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