Clinicopathologic features, treatments, and survival of patients with ectopic Cushing's syndrome from neuroendocrine tumours: data from an Italian multicentre study

Abstract

Introduction: Literature on ectopic Cushing syndrome (ECS) and NET is scarce. Aim(s): This is the first Italian multicenter study on clinicopathologic features, treatment and survival of ECS-NET patients. Materials and Methods: Retrospective analysis of data on ECS-NET from 17 centers, obtained by a questionnaire. Results: 110 patients, 58.2% females, mean +/- SD age at diagnosis 49.5 +/- 15.9 yr. Clinical presentation: hypertension 89.1%, diabetes mellitus 65.5%, proximal myopathy 70.9%, weight loss 29.1%, skin fragility 54.5%, hypercoagulability 30%, osteoporosis 48.2%, psychiatric disease 34.5%. NET prevalence: 40.9% bronchial carcinoids (BC), 22.7% occult, 15.5% pancreatic pNET, 6.4% pheochromocytomas, 5.5% thymic carcinoids (TC), 3.6% SCLC, other (5.4%). pNET tumor diameter was larger than BC (p = 0.002). Distant metastases were more prevalent in pNET, SCLC and TC than in BC and occult. Curative surgery was performed in 56.7% (76.5% of BC, 11% of pNET). Adrenalectomy in 28.2%. Steroidogenesis inhibitors were used in 94.9%, SA in 54.5%. 5 yr OS was higher in BC vs. pNET and occult (p = 0.009), in G1 vs. G2-G3(p = 0.007), in patients with S-U cortisol and ACTH <5ULN, without ipokaliemia (p < 0.002) and metastases (p = 0.019) with NET surgery (p < 0.01) and adrenalectomy. Conclusion: BC are the main ECS-NET with high curative surgical rate and best survival. 23%are occult with poorer prognosis than BC. Type of NET, grading, distant metastases, severity of hypercortisolism are main prognostic factors. A multimodal treatment, including surgery and adrenalectomy, can prolong survival.