Steroid-induced adrenal insufficiency in children with nephrotic syndrome: a systematic review

Idiopathic nephrotic syndrome (NS) is the most common glomerular disease in children. While corticosteroids remain the first-line treatment for inducing remission, their prolonged or frequent use can suppress the hypothalamic-pituitary-adrenal (HPA) axis, potentially leading to adrenal insufficiency (AI). However, the true burden of this complication remains poorly understood and inconsistently reported. This study aimed to systematically evaluate the prevalence, diagnostic methods, risk factors, and clinical implications of steroid-induced AI in children with NS.

A systematic search of Medline was conducted up to October 3, 2025, and the references of relevant publications were also hand-searched for eligible studies. We looked for studies that assessed adrenal function or AI in pediatric patients with NS treated with corticosteroids. Only English-language studies were included; case reports, abstracts, and reviews were excluded. In total, 13 studies involving 516 pediatric patients met the inclusion criteria. The review was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA 2020) guidelines and was registered in the PROSPERO database (CRD420251082353, June 27, 2025). Due to methodological heterogeneity, a narrative synthesis was performed.

The reported prevalence of AI ranged from 5.9 to 92.9%, largely influenced by the diagnostic test used and the timing of assessment. Seven different testing methods were identified, with the 2-h ACTH stimulation test demonstrating the highest diagnostic yield. Definitions of AI and cortisol cutoff values varied considerably across studies. AI was more commonly observed in children with frequently relapsing or steroid-dependent NS, as well as in those with prolonged or repeated exposure to corticosteroids. Associations with age were inconsistent. AI was also linked to an increased risk of relapse, particularly during infections. Children with suppressed adrenal function may be at risk of adrenal crisis if not administered stress-dose corticosteroids during periods of physiological stress.

Included studies were mostly small, single-center, and methodologically heterogeneous. There was a lack of consensus on diagnostic criteria and limited long-term follow-up data. Steroid-induced AI is a common and potentially under-recognized complication in children with idiopathic NS, especially in high-risk groups. Due to inconsistent diagnostic practices, the actual prevalence of AI is unclear. There is a critical need for further research, standardized testing protocols, and clinical guidelines. Clinicians may consider screening for AI in children with high cumulative steroid exposure and consider cortisol replacement accordingly.