Endocrine Abstracts (2012) 29 P346

ACTH-dependent Cushing's syndrome secondary to an ectopic source of ACTH/CRH: three clinical cases with different prognosis and outcome

B. Fibbi, C. Maggioli, L. Vannucci, E. Giurgola, M. De Feo, L. Petrone, G. Parenti, M. Mannelli, G. Forti & C. Pupilli


Careggi Hospital and University of Florence, Florence, Italy.


Introduction: Ectopic ACTH-dependent Cushing’s syndrome (ACS) may present with different clinical pictures and it may represent a diagnostic challenge.

Methods: We describe the clinical presentation and the laboratory, imaging and pathologic findings of three patients with ectopic ACS.

Results: Case 1. A 31-year-old man with a 1-year history of spontaneous rib and vertebral fractures was admitted to our hospital for ACS evaluation. He displayed typical cushingoid features. Pituitary magnetic resonance imaging (MRI), chest/abdomen computed tomography (CT) and whole body Octreoscan (WBO) were unremarkable. Petrosal sinus sampling with corticotrophin-releasing hormone (CRH) stimulation was negative. A (68Ga)DOTATOC-PET/CT showed a 7 mm-pulmonary nodule that was excised and diagnosed as a typical carcinoid. Six months later, he showed nearly complete biochemical and clinical recovery.

Case 2. A 72-year-old man was referred to endocrinological evaluation for hyponatremia. Biochemical analysis revealed ACS, thrombocytopenia and monoclonal gammopathy. Chest CT showed a widespread mass in the left lung. Both the cytology on bronchoalveolar lavage and the osteomedullary biopsy revealed neuroendocrine-differentiated cells. He started chemotherapy, but died after few weeks.

Case 3. A 66-year-old man with a 2-year history of diabetes mellitus and hypogonadotropic hypogonadism and recent leg swelling was referred to our center for ACS. He didn’t show cushingoid features except for muscle hypotrophy. Melanodermia, marked hypokalemia and psychosis were present. Chest/abdomen CT and WBO were negative. Pituitary MRI showed a microadenoma and petrosal sinus sampling with CRH stimulation was inconclusive. Despite ketokonazole and mifepristone treatment, he became hemodynamically unstable for a massive bilateral pleural effusion and sepsis, and rapidly died. The post-mortem result of cytologic analysis on pleural liquid was positive for adenocarcinoma.

Conclusions: Ectopic ACS can be caused by tumors with different degrees of malignancy, thus conditioning different prognosis. The disease course can also be complicated by the difficulty in tumor localization with conventional imaging techniques.

Declaration of interest: The authors declare that there is no conflict of interest that could be perceived as prejudicing the impartiality of the research project.

Funding: This research did not receive any specific grant from any funding agency in the public, commercial or not-for-profit sector.