Paediatric and adolescent ectopic Cushing's syndrome: systematic review

Objective The data on clinical, biochemical, radiological characteristics, and outcomes in paediatric ectopic adrenocorticotropic hormone syndrome (EAS) are limited owing to rarity of the condition. We report three new cases and perform a systematic review of paediatric EAS. Design and Method Case records of paediatric and adolescent EAS patient's <= 20 years presenting at our centre between 1997 and 2021 were retrospectively reviewed, and a systematic review of the literature published between January 1970 and December 2022 was performed. Results A total of 161 patients including 3 new patients from our centre were identified. Bronchial neuroendocrine tumours (NET) (28.5%), thymic NET (22.9%), primitive cell-derived tumours (18.6%), and gastro-entero-pancreatic-NET (13.7%) were the common causes. Primitive cell-derived tumours were the most common in the first decade (24/45, 53.4%) and were the largest (82 [60-100] mm), whereas bronchial NETs predominated during the second decade (42/116, 36.2%) and were the smallest (15 [10-25] mm). Computed tomography localized 92.9% (118/127) of paediatric EAS patients. Immediate postoperative remission was attained in 77.9% (88/113) patients, whereas 30.4% (24/79) relapsed over a median (IQR) period of 13 (8-36) months. Over a median (IQR) follow-up of 2 (0.6-4.6) years, 31.4% of patients died. The median survival was higher in bronchial NET than in other tumour groups. Distant metastasis and tumour size were independent negative predictors of survival. Conclusions Aetiological profile of paediatric and adolescent EAS is distinct from that of adults. Bronchial NETs have the best long-term survival, whereas distant metastasis and tumour size predict poor survival.