To document the frequency and outcome of endocrine involvement in pediatric-onset Langerhans' cell histiocytosis (LCH), and the association with other types of organ involvement.

This retrospective nationwide multicenter study involved 589 patients with pediatric-onset LCH, 148 of whom had endocrine dysfunction. Median follow-up was 11.6 years.

Pituitary dysfunction was present in 145 patients, and 141 had diabetes insipidus (DI). The estimated 10-year risks of pituitary involvement were 24.2% ± 1.8%. GH deficiency occurred in 61 patients. Median age at onset was 2.8 years for LCH, 3.9 years for DI, and 7.7 years for GH deficiency. The risk of cranial involvement; ear, nose, and throat involvement; pneumothorax; and cholangitis was significantly higher in patients with endocrinopathy. The chronology of episodes did not support a causal link between pituitary involvement and involvement of other organs. Systemic treatment of LCH did not prevent pituitary involvement. The most severe complication was a neurodegenerative syndrome, which affected 4.3% and 10.8% of patients, respectively, 5 and 15 years after initial diagnosis, and appeared to be linked to pituitary involvement.

Patients who develop endocrine LCH disorders are at a high risk of neurodegenerative LCH and require long-term follow-up.