Endocrine Abstracts

Introduction: Ectopic Cushing’s syndrome (ECS) is a rare disease with limited and error-prone published data on the epidemiology, clinical presentation and diagnosis of ECS.

Objectives: This study aims to examine the clinical course of patients with ECS in relation to the primary tumor localization.

Methods: Thirty-five consecutive ECS patients at a tertiary clinical center were analyzed. The clinical, biochemical (including CRH/desmopressin tests/BIPSS in selected cases) and imaging (CT/MRI, somatostatin receptor imaging, and FDG PET/CT) assessment were performed. Three patients with SCLC were excluded from further analysis.

Results: The primary lesion was identified in 28/32 patients. Neuroendocrine tumor (NET) constituted 47% of all ECS (60% gastroenteropancreatic (GEP-NETs), 40% thoracic (1 thymic and 5 pulmonary carcinoids (PC)). The median follow-up was 12 months, in the PCs was significantly higher compared to the GEP-NETs (54 vs 11 months). There were 18 deaths (56.25%). In patients with PC, 1 patient died due to pulmonary embolism, while in the GEP-NETs 8(89%) patients died due to disease progression. In patients with disseminated disease 1 patient underwent chemotherapy, 4 were treated surgically, 4 with PPRT. 5/6 of PCs underwent radical surgical treatment, all were treated with steroidogenesis inhibitors. There was a significant difference in the mean age at diagnosis between women and men (F=64.25 vs M=51.06 years, P=0.02). The dominant clinical feature for the entire group were muscle weakness (78.13%) and edema (62.5%). Typical changes in appearance characteristic of Cushing’s syndrome occurred in 6(16%) of patients, in 4/5 PC. PCs comparing to other ECSs showed more frequently striae (80% vs 14.81%, P=0.003), fat tissue redistribution (80% vs 51.85%, P=0.10). No PC experienced weight loss, observed in 11(47.4%) others ECSs (P=0.05). The median nocturnal serum cortisol was higher in patients with NETs compared to other ECSs (61 vs 25.5 μg/dl, P=0,058). In the GEP-NETs, the median concentration of both morning cortisol (71 vs 42 μg/dl, P=0.02) and midnight cortisol (64 vs 25.5 μg/dl. P=0.008) was higher than in other ECSs. In PCs, there was a strong correlation between the midnight serum cortisol and the severity of hypocalcemia (Spearman’s coefficient −0.90, P<0.05), which was not present in GEP-NETs.

Conclusion: The clinical picture of ECS is highly variable. PCs tend to display more prevalent classic symptoms of CS and notably extended survival times compared to other ECSs. Further studies are needed to understand the natural history of ECS and to improve the diagnosis and treatment outcomes of this rare disease.