Cushing's syndrome in children and adolescents: a Danish nationwide population-based cohort study

TY - JOUR

T1 - Cushing's syndrome in children and adolescents

T2 - a Danish nationwide population-based cohort study

AU - Holst, Johanne Marie

AU - Horváth-Puhó, Erzsébet

AU - Jensen, Rikke Beck

AU - Rix, Mariane

AU - Kristensen, Kurt

AU - Hertel, Niels Thomas

AU - Dekkers, Olaf M

AU - Sørensen, Henrik Toft

AU - Juul, Anders

AU - Jørgensen, Jens Otto L

N1 - © 2017 European Society of Endocrinology.

PY - 2017/5

Y1 - 2017/5

N2 - 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.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 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.

AB - 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.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 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.

KW - Adolescent

KW - Child

KW - Child, Preschool

KW - Cohort Studies

KW - Cushing Syndrome/diagnosis

KW - Denmark/epidemiology

KW - Female

KW - Follow-Up Studies

KW - Humans

KW - Infant

KW - Infant, Newborn

KW - Male

KW - Population Surveillance/methods

KW - Young Adult

U2 - 10.1530/eje-16-0843

DO - 10.1530/eje-16-0843

M3 - Journal article

C2 - 28179451

SN - 0804-4643

VL - 176

SP - 567

EP - 574

JO - European Journal of Endocrinology

JF - European Journal of Endocrinology

IS - 5

ER -