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

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Abstract

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 Metyrapone treatment was initiated but then withdrawn because the patient spontaneously recovered and cortisol metabolism gradually normalized within 3 weeks.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.

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Acknowledgments

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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Authors and Affiliations

  1. Division of Endocrinology, Department of Medicine, Helsinki University Central Hospital, P.O. Box 340, 00290, Helsinki, Finland

    Camilla Schalin-Jäntti & Timo Sane

  2. University of Helsinki, Helsinki, Finland

    Camilla Schalin-Jäntti

  3. Department of Pathology, Haartman Institute, University of Helsinki, Helsinki, Finland

    Johanna Arola

  4. HUSLAB, Helsinki University Hospital, Helsinki, Finland

    Johanna Arola

  5. Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Canada

    Sylvia L. Asa

Authors
  1. Camilla Schalin-Jäntti
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  2. Sylvia L. Asa
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  4. Timo Sane
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Correspondence to Camilla Schalin-Jäntti.

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Schalin-Jäntti, C., Asa, S.L., Arola, J. et al. Recurrent Acute-Onset Cushing’s Syndrome 6 Years after Removal of a Thymic Neuroendocrine Carcinoma: From Ectopic ACTH to CRH. Endocr Pathol 24, 25–29 (2013). https://doi.org/10.1007/s12022-012-9228-5

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  • DOI: https://doi.org/10.1007/s12022-012-9228-5

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