Abstract / Summary
Abstract Growth hormone replacement therapy (GHRT) is commonly used to treat growth hormone deficiency (GHD) after craniopharyngioma (CP) surgery, but its metabolic consequences in pediatric patients remain incompletely characterized. This study aimed to investigate serum metabolomic alterations associated with GHRT in pediatric patients with postoperative childhood-onset CP. We conducted an untargeted serum metabolomics study in 60 pediatric patients with childhood-onset CP following surgery, including 32 patients receiving GHRT and 28 patients not receiving GHRT. Clinical data and biochemical parameters were collected. Serum metabolites were profiled using ultra-high-performance liquid chromatography–tandem mass spectrometry (UHPLC-MS/MS). Differential metabolite identification, pathway enrichment analysis, and correlation analyses were conducted to characterize GHRT-associated metabolic signatures and their relationships with clinical indicators. Patients receiving GHRT had higher insulin-like growth factor 1 (IGF-1) levels, whereas conventional lipid parameters did not differ significantly between groups. HOMA-IR was higher and QUICKI was lower in the GHRT group. Using stringent criteria of VIP > 1, BH-FDR q < 0.05, and |log₂FC| > 2, 10 key positive-ion metabolites were identified, including phosphatidylcholine, triglycerides, sphingomyelins (SMs), and 3,5-diiodo-L-thyronine (T2). Nine lipid-related metabolites were higher and T2 was lower in the GHRT group. These associations remained significant after adjustment for chronological age and postoperative interval and in sensitivity analyses additionally accounting for sex-steroid replacement. GHRT exposure in children and adolescents with postoperative childhood-onset CP was associated with distinct serum metabolomic signatures, predominantly involving phosphatidylcholine, triglycerides, and SMs. These findings represent exploratory associations and require confirmation in longitudinal studies before treatment-related or clinical implications can be established.