ESPE Abstracts (2015) 84 P-2-183

24-H Urinary Free Cortisol as a Screening Test for Cushing's Syndrome in Children

Lucy Shapiroa, Shezan Elahia, Joe Balieyb, Les Perryc, Lee Martina, Ashley Grossmand, Scott Akkera, John Monsona, William Drakea, Martin Savagea & Helen Storra

aCentre for Endocrinology, William Harvey Research Institute, Queen Mary University of London, Barts and the London School of Medicine and Dentistry, London, UK; bDepartment of Clinical Biochemistry, Barts Health NHS Trust, London, UK; cPathology Department, Croydon Health Services, Croydon, UK; dOxford Centre for Diabetes, Endocrinology and Metabolism, University of Oxford, Oxford, UK

Background: Cushing’s 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: Cushing’s 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.