Paediatric Cushing syndrome: a prospective, multisite, observational cohort study
Christina Tatsi1, Crystal Kamilaris1, Meg Keil2
1Unit on Hypothalamic and Pituitary Disorders, National Institutes of Health, Bethesda, MD, USA.
Insights
Paediatric Cushing syndrome, a rare condition, presents with varied symptoms. This study details characteristics, complications, and outcomes in a large cohort to improve diagnosis and management of this rare endocrine disorder.
Area of Science:
- Pediatric Endocrinology
- Rare Endocrine Diseases
- Cushing Syndrome Pathophysiology
Background:
- Paediatric endogenous Cushing syndrome is a rare endocrine disorder with diverse clinical presentations.
- Accurate diagnosis and management are often challenging due to symptom variability.
- Understanding the specific characteristics of paediatric Cushing syndrome is crucial for effective patient care.
Purpose of the Study:
- To describe the anthropometric, clinical, and biochemical features of paediatric endogenous Cushing syndrome.
- To identify common complications and long-term outcomes in children with this condition.
- To provide data that aids in the diagnosis, treatment, and management of paediatric Cushing syndrome.
Main Methods:
- A prospective, multisite cohort study involving children and adolescents (≤18 years) diagnosed with Cushing syndrome.
- Collection of clinical, biochemical, and imaging data, along with post-operative course monitoring.
- Analysis of data from 342 paediatric patients with Cushing syndrome.
Main Results:
- The study included 342 patients: 76% with Cushing disease, 22% with adrenal-associated Cushing syndrome, and 2% with ectopic Cushing syndrome.
- Diagnosis occurred a median of 2 years after symptom onset, with adrenal-associated cases diagnosed youngest.
- Common complications included hypertension (52%), hyperglycaemia (30%), elevated ALT (64%), and dyslipidaemia (48%).
- Ectopic Cushing syndrome showed significantly higher urinary free cortisol levels compared to other subtypes.
Conclusions:
- This large cohort provides extensive insights into paediatric Cushing syndrome, aiding diagnostic workup.
- Findings can inform preventative strategies and follow-up protocols for children with this rare endocrine condition.
- Understanding subtype-specific features and common complications is key for optimizing patient management.
Background:
Paediatric endogenous Cushing syndrome is a rare condition with variable signs and symptoms of presentation. We studied a large cohort of paediatric patients with endogenous Cushing syndrome with the aim of describing anthropometric, clinical, and biochemical characteristics as well as associated complications and outcomes to aid diagnosis, treatment, and management.
Methods:
In this prospective, multisite cohort study, we studied children and adolescents (≤18 years at time of presentation) with a diagnosis of Cushing syndrome. Patients had either received their initial diagnosis and evaluation at the Eunice Kennedy Shriver National Institute of Child Health and Human Development (Bethesda, MD, USA) or been referred from other centres in the USA or outside the USA. We collected participants' clinical, biochemical, and imaging findings and recorded their post-operative course until their latest appointment.
Findings:
Of 342 paediatric patients with a diagnosis of Cushing syndrome, 193 (56%) were female and 149 (44%) male. 261 (76%) patients had corticotroph pituitary neuroendocrine tumours (Cushing disease), 74 (22%) had adrenal-associated Cushing syndrome, and seven (2%) had ectopic Cushing syndrome. Patients were diagnosed at a median of 2 years (IQR 1·0-3·0) after the first concerning sign or symptom, and 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; p<0·0001). Body-mass index z-scores did not differ between the diagnostic groups (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; p=0·26). Baseline biochemical screening for cortisol and adrenocorticotropin 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 (fold change in median cortisol concentration from upper limit of normal: 15·5 [IQR 12·7-18·0]) than patients with adrenal-associated Cushing syndrome (1·5 [0·6-5·7]) or Cushing disease (3·9 [2·3-6·9]; p<0·0001). Common complications of endogenous Cushing syndrome were hypertension (147 [52%] of 281 patients), hyperglycaemia (78 [30%] of 260 patients), elevated alanine transaminase (145 [64%] of 227 patients), and dyslipidaemia (105 [48%] of 219 patients). Long-term recurrence was noted in at least 16 (8%) of 195 patients with Cushing disease.
Interpretation:
This extensive description of a unique cohort of paediatric patients with Cushing syndrome has the potential to inform diagnostic workup, preventative actions, and follow-up of children with this rare endocrine condition.
Funding:
Intramural Research Program, Eunice Kennedy Shriver National Institute of Child Health & Human Development, National Institutes of Health.
