Background: Cushings syndrome (CS) in children remains a challenge to diagnose and exclude. Published diagnostic guidelines for CS are heavily based upon adult data. The use of 24-h urinary free cortisol (UFC) measurements in the diagnosis of adult CS may have limited use. There is little data on the utility of 24-h UFC in children.
Objective and hypotheses: We hypothesised that 24-h UFC is a robust and reliable screening test in children. The study aims to assess its screening accuracy in paediatric patients referred for evaluation of possible CS.
Method: Retrospective study of children referred to our centre between 1982-2014 was undertaken. 68 patients: 19 controls (9M) and 49 CS cases (30M), which included: Cushings Disease (CD) (39 patients, 25M), bilateral micronodular adrenocortical disease (BMAD) (8 patients, 4M), ectopic ACTH secreting tumours (two patients, 1M). All patient groups had either one or several 24-h UFC collections analysed by radioassay, immunoassay or liquid chromatography-mass spectrometry. Data was measured using the Receiver Operating Characteristics (ROC) analysis and expressed as area under the curve (AUC) and by an independent 2 tailed t-test.
Results: The diagnostic accuracy of 24-h UFC was excellent (0.98, 95% CI 0.946-1.00), with sensitivity and specificity for CS being 94% and 90%, respectively. 24-h UFC levels were higher in CS secondary to peripheral causes (ectopic CS or BMAD) as compared to CD (mean: 1430 vs 885 nmol/24-h; P=0.025). For CD, the mean 24-h UFC values were higher in males compared to females (P=0.02).
Conclusion: 24-h UFC is a reliable and practical screening tool with excellent diagnostic accuracy for paediatric CS. Children with a single high 24-h UFC, despite a normal overall mean, should be thoroughly investigated for CS. UFC measurements were significantly higher in male compared to female CD patients and in peripheral causes of CS compared to CD.
01 - 03 Oct 2015
European Society for Paediatric Endocrinology