ESPE Yearbook of Paediatric Endocrinology

Brief Summary: This large patient cohort of children with endogenous Cushing syndrome describes their anthropometric, clinical, and biochemical characteristics, as well as their associated complications and outcomes. The findings inform diagnosis, treatment, and management.

Comment: Endogenous Cushing syndrome is rare in children and adolescents, and has variable manifestations (1-6). This prospective, multicenter cohort of 342 children and adolescents aged ≤18 years at diagnosis of Cushing syndrome collected clinical, biochemical, and imaging data until their latest appointment. 193 (56%) were female, 149 (44%) male, 261 (76%) had Cushing disease, 74 (22%) had adrenal-associated Cushing syndrome, and 7 (2%) had ectopic Cushing syndrome. Delay in diagnosis was median 2 years (IQR 1·0-3·0) after the first concerning sign or symptom. Patients with adrenal-associated Cushing syndrome were the youngest at diagnosis (median 10·4 years [IQR 7·4-13·6] vs 13·0 years [10·5-15·3] for Cushing disease vs 13·4 years [11·0-13·7] for ectopic Cushing syndrome). Body-mass index z-scores did not differ between subtypes (1·90 [1·19-2·34] for adrenal-associated Cushing syndrome vs 2·18 [1·60-2·56] for Cushing disease vs 2·22 [1·42-2·35] for ectopic Cushing syndrome). Baseline biochemical screening for cortisol and ACTH at diagnosis showed overlapping results between subtypes, and especially between Cushing disease and ectopic Cushing syndrome. However, patients with ectopic Cushing syndrome had higher urinary free cortisol than thosse with adrenal-associated Cushing syndrome or Cushing disease.

Common complications of endogenous Cushing syndrome were decreased growth velocity, hypertension, hyperglycemia, elevated alanine transaminase, and dyslipidemia. Long-term recurrence was noted in at least 16/195 (8%) patients with Cushing disease. Recurrence was reported up to 8 years after surgery. This suggests that annual screening for recurrence should be performed in children for a minimum of 10 years after remission, and possibly longer, as recommended in adults.

In conclusion, this uniquely large patient cohort provides detailed information on the diagnostic evaluation of patients with this rare endocrine condition, as well as for screening for its complications. The prognosis of Cushing syndrome remains excellent if the diagnosis and management is performed by experienced specialists.

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