Incidence of Adrenal Insufficiency in Patients With High-Risk Neuroblastoma: A Single-Institution Analysis

Background: Neuroblastoma is the most common extracranial solid tumor in children, with about half of cases classified as high risk. Treatment varies by risk level, with high-risk patients undergoing aggressive multimodal therapy. While long-term survival has improved, survivors face significant risks of late treatment effects, including adrenal insufficiency. This study investigates the incidence of adrenal insufficiency among neuroblastoma patients of varying disease risk.

Procedure: This retrospective cohort study at a single tertiary children's hospital reviewed records from 1998 to 2021, identifying 370 neuroblastoma patients, with 137 having complete risk stratification. The primary outcome was the incidence of adrenal insufficiency, diagnosed via clinical evaluation, and compared by risk group.

Results: Among 137 patients with neuroblastoma, nine (12.0%) high-risk and three (4.9%) non-high-risk patients were diagnosed with adrenal insufficiency. The cumulative incidence of adrenal insufficiency at 3 years after neuroblastoma diagnosis was 9.9% in high-risk and 3.5% in non-high-risk patients. Among high-risk neuroblastoma patients with adrenal insufficiency, median time to adrenal insufficiency diagnosis was 10.2 months from neuroblastoma diagnosis, with cases more commonly occurring in patients with adrenal primary tumors (p = 0.0234). There were no other significant differences in demographic or clinical characteristics between high-risk patients with and without adrenal insufficiency.

Conclusions: Adrenal insufficiency occurs more commonly in children with high-risk neuroblastoma than in non-high-risk cases, particularly those with adrenal primary tumors. These findings underscore the need for vigilant monitoring and screening for adrenal insufficiency during and after treatment. Future research should include larger, multi-institutional cohorts to better understand risk factors and optimize screening protocols.