Cushing's Syndrome in Children and Adolescents: A Danish Nationwide Population-Based Cohort Study

OBJECTIVE: Cushing's syndrome (CS) affects all age groups, but epidemiologic data in young pa-tients are very limited. We therefore examined the incidence, prevalence, and hospital morbidity of CS in children and adolescents.

DESIGN: In a nationwide cohort study we included all Danish citizens aged 0-20 years from 1977 to 2012. Data were obtained from the Danish National Patient Registry using the International Classi-fication of Diseases (ICD) codes and the Danish Civil Registration System. The diagnosis and treatment were validated by means of individual patient charts. Incidence rate of CS patients aged 0-20 years at diagnosis were computed (standardized to the age and sex distribution of the Danish population). The patients were followed for a maximum of 36 years. Standardized incidence ratios (SIRs) of different hospital-recorded outcomes based on the ICD codes in patients with CS com-pared to the general population were assessed.

RESULTS: We identified a total of 40 pediatric patients with CS, yielding an annual incidence of 0.89 cases/106 population (95% confidence interval (CI) = 0.63-1.16). The median age at time of diagno-sis was 13.8 years (interquartile range 10.5-18.2 years), 58% were female, and 70% had adrenocor-ticotropic hormone-producing pituitary adenomas. During follow-up, CS patients (excluding three malignant cases) were at increased risk of being diagnosed with infections (standardized incidence ratio (SIR) 3.24, 95% CI 1.05-7.54) and infertility (SIR 4.56, 95% CI 1.48-10.63). The three pa-tients with an adrenocortical carcinoma died shortly after diagnosis, but mortality was not increased in the remaining patients.

CONCLUSIONS: CS is rare in the pediatric population. The risk of morbidity related to infections and infertility is elevated and merits further attention.