8598 Heterogeneous course of ectopic Cushing's syndrome (EAS) - does the location of the primary tumor affect the clinical picture and the outcome?
Authors: Gamrat A , Minasyan M , Komisarz-Calik M , Paleń-Tytko J , Opalińska M , Hubalewska-Dydejczyk A , Gilis-Januszewska A 
Published: October 2024

Disclosure: A. Gamrat: None. M. Minasyan: None. M. Komisarz-Calik: None. J. Paleń-Tytko: None. M. Opalińska: None. A. Hubalewska-Dydejczyk: None. A. Gilis-Januszewska: None.

Introduction: Ectopic Cushing's syndrome (EAS) is a very rare disease with limited and error-prone published data on the epidemiology, clinical presentation and diagnosis of EAS. Objectives: This study aims to examine the clinical course of patients with EAS depending on the primary tumor localization. Methods: We retrospectively analyzed the data of 36 consecutive EAS patients diagnosed between 2020-2023 at the tertiary clinical center. The diagnosis of EAS was based on the clinical presentation and biochemical work up including CRH/desmopressin tests/BIPS in selected cases. The imaging included CT/MRI, somatostatin receptor imaging and FDG PET/CT. Results: The primary lesion causing EAS was identified in 32 patients, 1 patient died before the source of ACTH overproduction was detected, in 3 patients the diagnosis is ongoing. The most common cause of EAS was neuroendocrine tumor (NET) (16/44,4%), of which 9/56,2% was gastroenteropancreatic NET (GEPNET), and 7/43,8% NET of the thorax (1 thymic and 6 pulmonary carcinoids (PC)). The median follow-up period was 12 months and in the PC group was significantly higher compared to the GEPNET group (56 vs 11 months p=0.05). There were 20 deaths/55%. In patients with PC, 1 patient died due to pulmonary embolism, while in the GEPNETs 8/89% of patients died (due to widely disseminated disease at diagnosis). In the group of disseminated patients, 1 patient underwent chemotherapy, 4 were treated surgically while 4 with PPRT. 5/6 patients with PC underwent radical surgical treatment, all were treated with steroidogenesis inhibitors. The dominant clinical feature for the entire group were muscle weakness (77%) and edema (61%). Typical changes in appearance characteristic of Cushing's syndrome occurred in 6/16% of patients, mainly with PC. Patients with PC compared to the other EAS presented more frequent striae (83.3%vs. 10.34%, p=0.001), redistribution of fat tissue (83,3 vs 46,57%, p=0,08) and weight gain (66,7% vs 26,7%, p=0,07). The median nocturnal serum cortisol was higher in patients with NETs compared to other EAS (59.5 ug/dL vs 25.5 ug/dL, p=0.032). In the GEPNET, the median serum morning (71 ug/dL vs 43.5 ug/dL p=0.03) and night cortisol concentration (64 ug/dL vs 26.3 ug/dL, p=0.02) was higher than in the group of other patients. In PC, there was a strong correlation between the morning cortisol level and the severity of hypokalemia (Spearman's coefficient -0.94, p&lt;0.05), which was not present in gastrointestinal neuroendocrine tumors. Conclusion: The clinical picture of EAS is highly variable and varies in EAS of different origins. The classic symptoms of Cushing's syndrome as well as significantly longer survival times are more common in lung and thymic carcinomas compared to other EAS. Further, multicenter studies are needed to understand the natural history, course of EAS and to improve the diagnosis and treatment outcomes of this rare disease.

Presentation: 6/2/2024