Ectopic ACTH Cushing's syndrome caused by a large-cell neuroendocrine lung carcinoma responding to desmopressin

Program: Abstracts - Orals, Featured Poster Presentations, and Posters
Session: SUN 29-49-Congenital Adrenal Hyperplasia & Ectopic Cushing's
Sunday, June 16, 2013: 1:45 PM-3:45 PM
Expo Halls ABC (Moscone Center)

Poster Board SUN-41
Veronique Pelletier*1, Isabelle Ferdinand2, Agnes Rakel1, Louis-Georges Ste-Marie3, Raymonde Chartrand2, Roula Albadine2 and André Lacroix4
1Centre hospitalier de l'Université de Montréal, Montreal, QC, Canada, 2Centre hospitalier de l'Université de Montréal, Montréal, QC, Canada, 3CHUM - Hopital Saint-Luc, Montreal, QC, Canada, 4Centre Hospitalier de l'Université de Montréal, Montreal, QC, Canada
Introduction: Establishing the source of ACTH can be challenging in patients with ACTH-dependent Cushing’s syndrome who carry several co-morbidities.

Clinical case: A non-smoking 44 year-old man experienced progressive central obesity, proximal muscle weakness, high blood pressure and emotional lability during the last 6 months. At admission, recent left femoral vein thrombosis and silent bilateral pulmonary emboli were found.

Investigation: Elevated cortisoluria (>10xULN), ACTH level (112 pmol/L), hypokalemia, and poor dexamethasone suppression suggested ectopic ACTH source despite possible pituitary lesion at MRI. ACTH (t0:59.0 pmol/L;peak t15 min:151.9 pmol/L) and cortisol were stimulated by desmopressin  but not by CRH.  A low central-to-peripheral ACTH gradient was found during inferior petrosal venous sinus sampling with desmopressin. Combination of ketoconazole and metyrapone were necessary to control hypercortisolism. The interpretation of CT-scan of thorax and indium-111 octreoscan were complicated by the presence of multiple pulmonary emboli; a right 4 cm thoracic cage lipoma did not show any uptake with FDG-PET and no other thoraco-abdominal lesion was identified. A second indium-111 octreoscan two weeks later showed a persistent uptake in a 3 mm left inferior lobe lung nodule that was first interpreted as a vascular thrombus; other sites of uptake had regressed during therapy with low-molecular weight heparin. A left inferior lobectomy was performed and plasma cortisol and ACTH decreased abruptly after the surgery requiring hydrocortisone replacement. A diagnosis of lung carcinoid was expected based on the progressive Cushing’s syndrome and absence of activity of lesion on FDG-PET; a neuroendocrine large-cell carcinoma with intense ACTH expression was found at pathology with metastasis in 2/4  resected lymph nodes. The patient was referred to pulmonary oncology team for adjuvant therapy.

Conclusion : Neuroendocrine large-cell carcinoma is an infrequent subtype of bronchopulmonary neuroendocrine tumors, representing less than 1% of them. Our literature review indicates that this is the second case report of ectopic ACTH syndrome and the first of positive response to desmopressin test related to a large-cell lung carcinoma. This case illustrates the diversity of clinical and phenotypic behavior of ACTH secreting neuroendocrine tumors.

1. Tsagarakis S et al, The Desmopressin and Combined CRH-DesmopressinTests in the Differential Diagnosis of ACTH-Dependent Cushing’s Syndrome: Constraints Imposed by the Expression of V2 Vasopressin Receptors in Tumors with Ectopic ACTH Secretion, J Clin Endocrinol Metab. 2002 Apr; 87(4):1646-53. 2. Alexandraki KI et al, The ectopic ACTH syndrome, Rev Endocr Metab Disord. 2010 Jun;11(2): 117-26. 3. Lin CS et al, Ectopic ACTH Syndrome Associated With Large-Cell Neuroendocrine Carcinoma of the Lung, Am J Med Sci. 2007 Dec;334(6):487-9. 4. Gustafsson BI et al, Bronchopulmonary neuroendocrine tumors, Cancer 2008 Jul 1;113(1):5-21. Review.

Disclosure: AL: Investigator, Novartis Pharmaceuticals, Editor, Up To Date, Consultant, Novartis Pharmaceuticals. Nothing to Disclose: VP, IF, AR, LGS, RC, RA

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