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 patients are very limited. We therefore examined the incidence, prevalence and hospital morbidity of CS in children and adolescents.


METHODS
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 Classification 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 compared 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/106population (95% confidence interval (CI) = 0.63-1.16). The median age at the time of diagnosis was 13.8 years (interquartile range: 10.5-18.2 years), 58% were female and 70% had adrenocorticotropic hormone-producing pituitary adenomas. During follow-up, CS patients (excluding three malignant cases) were at increased risk of being diagnosed with infections (SIR: 3.24, 95% CI: 1.05-7.54) and infertility (SIR: 4.56, 95% CI: 1.48-10.63). The three patients 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.
Departments of Internal Medicine and Endocrinology.
Johanne Marie
JM
Holst
Departments of Clinical EpidemiologyAarhus University Hospital, Aarhus, Denmark.
Erzsébet
E
Horváth-Puhó
Department of Growth and ReproductionRigshospitalet, University of Copenhagen, Copenhagen, Denmark.
Rikke Beck
RB
Jensen
Department of PediatricsAalborg University Hospital, Aalborg, Denmark.
Mariane
M
Rix
Department of PediatricsAarhus University Hospital, Aarhus, Denmark.
Kurt
K
Kristensen
Hans Christian Andersen Children's HospitalOdense University Hospital, Odense, Denmark.
Niels Thomas
NT
Hertel
Departments of Clinical EpidemiologyAarhus University Hospital, Aarhus, Denmark.
Olaf M
OM
Dekkers
Departments of Clinical EpidemiologyAarhus University Hospital, Aarhus, Denmark.
Henrik Toft
HT
Sørensen
Department of Growth and ReproductionRigshospitalet, University of Copenhagen, Copenhagen, Denmark.
Anders
A
Juul
Departments of Internal Medicine and Endocrinology.
Jens Otto L
JOL
Jørgensen
D000293:Adolescent; D002648:Child; D002675:Child, Preschool; D015331:Cohort Studies; D003480:Cushing Syndrome / Q000175:diagnosis* / Q000453:epidemiology* / Q000601:surgery; D003718:Denmark / Q000453:epidemiology; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D011159:Population Surveillance / Q000379:methods; D055815:Young Adult