Prognostic factors in ectopic Cushing's syndrome due to neuroendocrine tumors: a multicenter study.
OBJECTIVE
Evidence is limited regarding outcome of patients with ectopic Cushing's syndrome (ECS) due to neuroendocrine tumors (NETs).


METHODS
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.
Section of EndocrinologyDepartment of Medicine, University of Verona, Verona, Italy.
Maria Vittoria
MV
Davi'
Section of EndocrinologyDepartment of Medicine, University of Verona, Verona, Italy.
Elisa
E
Cosaro
Endocrinology UnitCatholic University of Sacred Heart, Policlinico A. Gemelli, Rome, Italy.
Serena
S
Piacentini
Internal MedicineDepartment of Clinical and Biological Sciences, University of Turin, San Luigi Gonzaga Hospital, Orbassano, Italy.
Giuseppe
G
Reimondo
Endocrinology UnitDepartment of Medicine DIMED, University Hospital, Padua, Italy.
Nora
N
Albiger
Clinica di Endocrinologia e Malattie del Metabolismo Ospedali Riuniti di AnconaAncona, Italy.
Giorgio
G
Arnaldi
Thyroid and Parathyroid Surgery UnitIstituto Nazionale per lo Studio e la Cura dei Tumori 'Fondazione G. Pascale' IRCCS, Napoli, Italy.
Antongiulio
A
Faggiano
Endocrinology and Diabetology UnitUniversity of Milan, Milan, Italy.
Giovanna
G
Mantovani
Unit of Gastrointestinal Medical Oncology and Neuroendocrine TumorsEuropean Institute of Oncology, IEO, Milan, Italy.
Nicola
N
Fazio
Oncological Endocrinology UnitDepartment of Medical Sciences, University of Turin, Turin, Italy.
Alessandro
A
Piovesan
Oncological Endocrinology UnitDepartment of Medical Sciences, University of Turin, Turin, Italy.
Emanuela
E
Arvat
EndocrinologyDiabetes, Metabolism and Clinical Nutrition Unit, University-Hospital S. Maria della Misericordia, Udine, Italy.
Franco
F
Grimaldi
Department of Experimental and Clinical Biomedical Sciences 'Mario Serio'University of Florence, Florence, Italy.
Letizia
L
Canu
Department of Experimental and Clinical Biomedical Sciences 'Mario Serio'University of Florence, Florence, Italy.
Massimo
M
Mannelli
Department of Clinical Sciences & Community HealthUniversity of Milan, Milan, Italy.|Neuroendocrine Research LaboratoryIstituto Auxologico Italiano, Milan, Italy.
Alberto Giacinto
AG
Ambrogio
Department of Clinical Sciences & Community HealthUniversity of Milan, Milan, Italy.|Neuroendocrine Research LaboratoryIstituto Auxologico Italiano, Milan, Italy.
Francesca
F
Pecori Giraldi
Internal MedicineDepartment of Medicine, DIMED, University of Padova, Padova, Italy.
Chiara
C
Martini
Department of Biomedical SciencesHumanitas University and Endocrinology Unit, Humanitas Research Hospital, Rozzano, Italy.
Andrea
A
Lania
EndocrinologyDepartment of Internal Medicine (DiMI), University of Genoa, Genoa, Italy.
Manuela
M
Albertelli
EndocrinologyDepartment of Internal Medicine (DiMI), IRCCS, AOU San Martino IST and Center of Excellence for Biomedical Research (CEBR), University of Genoa, Genoa, Italy.
Diego
D
Ferone
Sezione di Endocrinologia e Medicina InternaDepartment of Medical Sciences, University of Ferrara, Ferrara, Italy.
Maria Chiara
MC
Zatelli
Department of Medical and Surgical SciencesUniversity of Bologna, Bologna, Italy.
Davide
D
Campana
Endocrinology DivisionDepartment of Clinical Medicine and Surgery, Università di Napoli Federico II, Naples, Italy.
Annamaria
A
Colao
Endocrinology UnitDepartment of Medicine DIMED, University Hospital, Padua, Italy.
Carla
C
Scaroni
Internal MedicineDepartment of Clinical and Biological Sciences, University of Turin, San Luigi Gonzaga Hospital, Orbassano, Italy.
Massimo
M
Terzolo
Endocrinology UnitCatholic University of Sacred Heart, Policlinico A. Gemelli, Rome, Italy.
Laura
L
De Marinis
OncologyUniversity of Verona, Verona, Italy.
Sara
S
Cingarlini
Department of Psychology and Cognitive SciencesUniversity of Trento, Trento, Italy.
Rocco
R
Micciolo
Section of EndocrinologyDepartment of Medicine, University of Verona, Verona, Italy.
Giuseppe
G
Francia
D000324:Adrenocorticotropic Hormone / Q000097:blood; D000328:Adult; D000368:Aged; D003480:Cushing Syndrome / Q000097:blood / Q000175:diagnosis* / Q000209:etiology* / Q000473:pathology*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D018358:Neuroendocrine Tumors / Q000097:blood / Q000150:complications* / Q000175:diagnosis* / Q000473:pathology; D011379:Prognosis; D012189:Retrospective Studies
D000324:Adrenocorticotropic Hormone