Endocrine Abstracts

Introduction

Ectopic Cushing’s syndrome (ECS) is a rare entity caused by ACTH secretion by a non-pituitary tumor. The management of these patients is challenging due to its low frequency and limited experienced. The objective of this study was to describe the patients with ECS treated in the Division of Endocrinology at the Ramón y Cajal University Hospital (Madrid, Spain) in the last six years.

Methods

Records of patients with ECS from 2016 to 2020 were retrospectively reviewed including clinical and biochemical data, imaging modalities to locate the non-pituitary source of ACTH production, management and follow up.

Results

The study group included 5 patients: two ECS secondary to bronchial carcinoid, one secondary to thymic carcinoma, one secondary to metastatic medullary thyroid carcinoma (MTC) and one occult ECS. Two were women and 4 men, median age of 44.6 (15.0–57.6) years at diagnosis. The specific clinical picture of Cushing syndrome developed in all patients with the exception of one patient with ECS due to bronchial carcinoid. Moreover, 2 patients presented hypertension, diabetes and obesity. Only the patient with ECS due to MTC had hypokalemia at diagnosis. The median urinary free cortisol and nocturnal salivary cortisol levels were 421.8 (30.6–47142) µg/24 h and 29.9 (3.4–2436) µg/dl, respectively, and the median plasma ACTH levels was 148.4 (46.1–929) pg/ml. The ectopic origin was confirmed by a combination of dynamic tests and imaging modalities. The tumor was identified in all patients except in one case, and 2 patients had metastatic dissemination. Primary treatment was surgery in 4 patients, one of them combined with chemotherapy and radiotherapy (thymic carcinoid), and medical treatment in 1 patient (occult ECS). Bilateral adrenalectomy was required in one patient. The medical treatments used to control hypercortisolism were ketoconazole in 3 patients and metopirone plus ketoconazole in one patient. After a mean follow-up of 67 months, 1 patient (MTC) died and 4 are still alive, 2 (bronchial carcinoid) cured and 2 (occult ECS and thymic carcinoid) with persistent/recurrent disease.

Conclusions

ECS is a rare disease caused by a wide spectrum of tumors with varied manifestations and associated increased morbidity and mortality. The most common tumor was bronchial carcinoid. Control of both tumor and hypercortisolism requires multiple treatment modalities, and surgery with removal of primary tumor was found to be the treatment of choice, if possible. Therefore, multidisciplinary management is recommended.