Endocrine Abstracts

Introduction: Ectopic Cushing Syndrome (ECS) is a rare disease associated with significant comorbidity. Among the causes of Cushing’s syndrome (CS), ACTH-producing extrahypophyseal tumours are rarely reported. The aim of our study is to describe the clinical, diagnostic and therapeutic characteristics of patients with ECS treated in our Endocrinology department over a 15-year period.

Methods: A cross-sectional unicentric retrospective study was designed. Patients diagnosed of ECS in our hospital between 2005 and 2019 were included. Epidemiological, clinical, diagnostic, therapeutic and evolutive variables were recorded.

Results: A total of 7 patients (5 males and 2 females) with a mean age of 52 years (29–77 years) were included. The median time from the onset of symptoms to hypercortisolism diagnosis was two months. Most frequent comorbidities were hypertension in 6 patients (86%), and diabetes mellitus in 5 patients (71%). Cushingoid phenotype, oedema of limbs and proximal weakness was observed with 86%, 86% and 71% each. Regarding laboratory tests alterations, hypokalemic metabolic alkalosis, hypertransaminasemia (71%) and leucocytosis (57%) were detected. Relating to Cushing syndrome diagnosis, the mean serum cortisol was of 52.44 µg/dl (20–98), urinary free cortisol 2624.28 µg/24 h (838–6246) and ACTH 193.7 pg/ml (75–271). The ectopic origin was confirmed whether by dynamic tests in a total of 5 patients (CRH stimulation test and/or inferior petrosal sinus sampling) and/or by radiological images in 7 patients (CT, MRI, Octreoscan, FDG-PET/CT and/or 68Ga-DOTANOC PET/CT). The responsible neoplasm could be identified by histology in 6 out of 7 cases. They were mostly pulmonary neuroendocrine tumours (4 carcinoids and 2 small cell carcinoma (SCLC), and 3 of them presented metastatic dissemination at diagnosis. Regarding therapeutic management of CS, ketoconazole and metyrapone were indicated in 6 and 3 respectively. The treatment of the primary tumour included surgery in two cases, surgery combined with systemic therapy (chemotherapy and somatostatin analogues) in one case, sunitinib and somatostatin analogues in other case and chemotherapy-only in two patients. At follow-up 3 have died and 4 remain alive (3 free of disease and one with stable disease).

Conclusions: ECS is associated with significant morbidity and mortality both due to the complications derived from excess cortisol production and the tumour itself and its dissemination. Mortality differs according to the underlying primary tumour, showing SCLC the poorest prognosis. This fact highlights the importance of both hypercortisolism control and the antitumor treatment, which requires a multidisciplinary management.