Maria Vittoria Davi'1, Elisa Cosaro1, Serena Piacentini2, Giuseppe Reimondo3, Nora Albiger4, Giorgio Arnaldi5, Antongiulio Faggiano6, Giovanna Mantovani7, Nicola Fazio8, Alessandro Piovesan9, Emanuela Arvat9, Franco Grimaldi10, Letizia Canu11, Massimo Mannelli11, Alberto Giacinto Ambrogio12,13, Francesca Pecori Giraldi12,13, Chiara Martini14, Andrea Lania15, Manuela Albertelli16, Diego Ferone17, Maria Chiara Zatelli18, Davide Campana19, Annamaria Colao20, Carla Scaroni4, Massimo Terzolo3, Laura De Marinis2, Sara Cingarlini21, Rocco Micciolo22, Giuseppe Francia1. 1. Section of EndocrinologyDepartment of Medicine, University of Verona, Verona, Italy. 2. Endocrinology UnitCatholic University of Sacred Heart, Policlinico A. Gemelli, Rome, Italy. 3. Internal MedicineDepartment of Clinical and Biological Sciences, University of Turin, San Luigi Gonzaga Hospital, Orbassano, Italy. 4. Endocrinology UnitDepartment of Medicine DIMED, University Hospital, Padua, Italy. 5. Clinica di Endocrinologia e Malattie del Metabolismo Ospedali Riuniti di AnconaAncona, Italy. 6. Thyroid and Parathyroid Surgery UnitIstituto Nazionale per lo Studio e la Cura dei Tumori 'Fondazione G. Pascale' IRCCS, Napoli, Italy. 7. Endocrinology and Diabetology UnitUniversity of Milan, Milan, Italy. 8. Unit of Gastrointestinal Medical Oncology and Neuroendocrine TumorsEuropean Institute of Oncology, IEO, Milan, Italy. 9. Oncological Endocrinology UnitDepartment of Medical Sciences, University of Turin, Turin, Italy. 10. EndocrinologyDiabetes, Metabolism and Clinical Nutrition Unit, University-Hospital S. Maria della Misericordia, Udine, Italy. 11. Department of Experimental and Clinical Biomedical Sciences 'Mario Serio'University of Florence, Florence, Italy. 12. Department of Clinical Sciences & Community HealthUniversity of Milan, Milan, Italy. 13. Neuroendocrine Research LaboratoryIstituto Auxologico Italiano, Milan, Italy. 14. Internal MedicineDepartment of Medicine, DIMED, University of Padova, Padova, Italy. 15. Department of Biomedical SciencesHumanitas University and Endocrinology Unit, Humanitas Research Hospital, Rozzano, Italy. 16. EndocrinologyDepartment of Internal Medicine (DiMI), University of Genoa, Genoa, Italy. 17. EndocrinologyDepartment of Internal Medicine (DiMI), IRCCS, AOU San Martino IST and Center of Excellence for Biomedical Research (CEBR), University of Genoa, Genoa, Italy. 18. Sezione di Endocrinologia e Medicina InternaDepartment of Medical Sciences, University of Ferrara, Ferrara, Italy. 19. Department of Medical and Surgical SciencesUniversity of Bologna, Bologna, Italy. 20. Endocrinology DivisionDepartment of Clinical Medicine and Surgery, Università di Napoli Federico II, Naples, Italy. 21. OncologyUniversity of Verona, Verona, Italy. 22. Department of Psychology and Cognitive SciencesUniversity of Trento, Trento, Italy.
Abstract
OBJECTIVE: Evidence is limited regarding outcome of patients with ectopic Cushing's syndrome (ECS) due to neuroendocrine tumors (NETs). DESIGN: We assessed the prognostic factors affecting the survival of patients with NETs and ECS. METHODS: Retrospective analysis of clinicopathological features, severity of hormonal syndrome, treatments from a large cohort of patients with NETs and ECS collected from 17 Italian centers. RESULTS: Our series included 110 patients, 58.2% female, with mean (±s.d.) age at diagnosis of 49.5 ± 15.9 years. The main sources of ectopic ACTH were bronchial carcinoids (BC) (40.9%), occult tumors (22.7%) and pancreatic (p)NETs (15.5%). Curative surgery was performed in 56.7% (70.2% of BC, 11% of pNETs). Overall survival was significantly higher in BC compared with pNETs and occult tumors (P = 0.033) and in G1-NETs compared with G2 and G3 (P = 0.007). Negative predictive factors for survival were severity of hypercortisolism (P < 0.02), hypokalemia (P = 0.001), diabetes mellitus (P = 0.0146) and distant metastases (P < 0.001). Improved survival was observed in patients who underwent NET removal (P < 0.001). Adrenalectomy improved short-term survival. CONCLUSIONS: Multiple factors affect prognosis of ECS patients: type of NET, grading, distant metastases, severity of hypercortisolism, hypokalemia and diabetes mellitus. BCs have the highest curative surgical rate and better survival compared with occult tumors and pNETs. Hypercortisolism plays a primary role in affecting outcome and quality of life; therefore, prompt and vigorous treatment of hormonal excess by NET surgery and medical therapy should be a key therapeutic goal. In refractory cases, adrenalectomy should be considered as it affects outcome positively at least in the first 2 years.
OBJECTIVE: Evidence is limited regarding outcome of patients with ectopic Cushing's syndrome (ECS) due to neuroendocrine tumors (NETs). DESIGN: We assessed the prognostic factors affecting the survival of patients with NETs and ECS. METHODS: Retrospective analysis of clinicopathological features, severity of hormonal syndrome, treatments from a large cohort of patients with NETs and ECS collected from 17 Italian centers. RESULTS: Our series included 110 patients, 58.2% female, with mean (±s.d.) age at diagnosis of 49.5 ± 15.9 years. The main sources of ectopic ACTH were bronchial carcinoids (BC) (40.9%), occult tumors (22.7%) and pancreatic (p)NETs (15.5%). Curative surgery was performed in 56.7% (70.2% of BC, 11% of pNETs). Overall survival was significantly higher in BC compared with pNETs and occult tumors (P = 0.033) and in G1-NETs compared with G2 and G3 (P = 0.007). Negative predictive factors for survival were severity of hypercortisolism (P < 0.02), hypokalemia (P = 0.001), diabetes mellitus (P = 0.0146) and distant metastases (P < 0.001). Improved survival was observed in patients who underwent NET removal (P < 0.001). Adrenalectomy improved short-term survival. CONCLUSIONS: Multiple factors affect prognosis of ECS patients: type of NET, grading, distant metastases, severity of hypercortisolism, hypokalemia and diabetes mellitus. BCs have the highest curative surgical rate and better survival compared with occult tumors and pNETs. Hypercortisolism plays a primary role in affecting outcome and quality of life; therefore, prompt and vigorous treatment of hormonal excess by NET surgery and medical therapy should be a key therapeutic goal. In refractory cases, adrenalectomy should be considered as it affects outcome positively at least in the first 2 years.
Authors: Taweesak Wannachalee; Adina F Turcu; Irina Bancos; Mouhammed Amir Habra; Anca M Avram; Hubert H Chuang; Steven G Waguespack; Richard J Auchus Journal: Clin Endocrinol (Oxf) Date: 2019-06-12 Impact factor: 3.478
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