Patients with langerhans cell histiocytosis and hypothalamic-pituitary involvement: insights from the HEROS study cohort.

Abstract

Purpose: Langerhans cell histiocytosis (LCH) is a rare disease involving multiple organs, including the endocrine system. This multicenter study aimed to characterize patients with hypothalamic- pituitary involvement in LCH.

Methods: The Hypopituitarism European NeuroEndocrine Association (ENEA) Rare Etiologies Observational Study (HEROS) platform invited ENEA members to include patients with rare pituitary diseases like LCH. Demographic data, presenting symptoms, hormonal profile, imaging tests, treatment, and prognosis were retrieved.

Results: Forty-eight patients (58% males) were included. Age at diagnosis was 22 ± 16.1 years, with 58% diagnosed as adults (> 18 years). The mean follow-up was 15.8 ± 10.6 years, 46% of the patients initially presented with bone lesions, 42% with lung involvement, and five were incidentally diagnosed. At diagnosis, 69% of the patients had arginine vasopressin deficiency (AVD), 42% had central hypogonadism, 25% hypothyroidism, and 12.5% hypocortisolism. Magnetic resonance imaging (MRI) was available in 41 patients, 73% of whom had pathology of the posterior pituitary/pituitary stalk. Visual disturbances were reported in only one patient. Diagnosis was histopathologically confirmed in all patients, mainly from extra-pituitary lesions. Transcranial biopsy was performed in five patients, and two underwent transsphenoidal intervention. During follow-up, 27% of the patients developed new AVD and five acquired new anterior pituitary hormone deficiency. There was no disease-related mortality during follow-up.

Conclusions: Patients with LCH and hypothalamic-pituitary involvement remained clinically stable during long-term follow-up. However, new hormonal deficits may develop years after diagnosis, with most patients ultimately experiencing AVD.