Endocrine Abstracts

Objective: To analyze long-term treatment outcomes and to determine prognostic factors affecting the survival of patients with ECS.

Matherials and methods: Retrospective, observational study on 147 patients (88 women, 59 men) with ECS diagnosed between 1990 and 2021. Various imaging studies were performed on all patients to find the source of ACTH producing neuroendocrine tumor (NET). Multivariable analysis was performed using a Cox proportional hazards model to define the independent prognostic factors.

Results: The median age at diagnosis was 40 years [28;54]. 89 patients (60,5%) had bronchopulmonary NET, 15 (10,2%) – thymic carcinoid, 5 – pancreatic NET, 6 – pheochromocytoma, 1– cecum NET, 1– appendix carcinoid tumor, 1 – medullary thyroid cancer and 29 (19,7%) patients had an occult NET. Mean time to diagnosis was 31 months, 11 patients (7,5%) had a cyclic course of disease. The most common complications in the active stage of disease were arterial hypertension (83,7%), osteoporosis with low-energy fractures (60%), type 2 DM (56,5%), cardiovascular disease (52,4%). The median follow-up period of patients was 36 months [11;73] with a maximum follow-up of 379 months. To the present date, the primary tumor was removed in 94 (63,9%) patients. Regional and distant metastases were revealed in 32 (21,8%). At the time of last observation, 62 patients (66%) had achieved stable remission, 12 (12,8%) had relapsed and received treatment with somatostatin analogs (n=9) or ketoconazole (n=1), and 38 patients (25,9%) had died from multiple organ failure (n=22), pulmonary embolism (n=5), sudden cardiac death (n=2), acute cerebrovascular accident (n=2), COVID-19 (n=3), complications of surgery (n=2), hip fracture (n=1), unknown cause (n=1). Bilateral adrenalectomy was performed on 45 patients (30,6%): due to occult tumor in 16 patients and incurable stage of disease in 29 patients. Multivariate analysis revealed that negative predictive factors for survival were: age ≥51 years at diagnosis, P<0,001 (HR 5,513 (2,286–13,293)), localization of NET in the pancreas, P=0,013 (HR 5,771 (1,473–23,176)), occult tumors, P=0,006 (HR 3,670 (1,461–9,216)) and LNSC ≥108,4 nmol/l, P=0,009 (HR 4,205 (1,433–12,334)). Bronchial NET, P=0,006 (HR 0,272 (0,109–0,684)) was a positive predictor of survival.

Conclusion: The survival rate ofECS is up to 75% over a mean follow-up of 36 months in spite of severe multiple complications associated with hypercortisolism. The severity of hypercortisolism, NET localization and occult tumors are negative factors associated with high mortality. Consequently, more aggressive treatment of hypercortisolism is potentially beneficial for survival in patients with extremely high LNSC.