Prognostic factors in ectopic Cushing’s syndrome due to neuroendocrine tumors: a multicenter study

Davi’ MV1Cosaro E2Piacentini S3Reimondo G4Albiger N5Arnaldi G6Faggiano A7Mantovani G8Fazio N9Piovesan A10Arvat E10Grimaldi F11Canu L12Mannelli M12Ambrogio AG13,14Pecori Giraldi F13,14Martini C15Lania A16Albertelli M17Ferone D18Zatelli MC19Campana D20Colao A21Scaroni C5Terzolo M4De Marinis L3Cingarlini S22Micciolo R23Francia G2.

Eur J Endocrinol. 2017 Apr; 176(4): 451-459



Evidence is limited regarding outcome of patients with ectopic Cushing’s syndrome (ECS) due to neuroendocrine tumors(NETs).


We assessed the prognostic factors affecting the survival of patients with NETs and ECS.


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.


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.


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.

Print Friendly, PDF & Email