Growth Hormone Deficiency and Systemic Metabolic Remodeling: Insights from Metabolomics and Lipidomics

Growth hormone (GH) deficiency (GHD) is a systemic endocrine-metabolic disorder affecting growth, body composition, substrate handling, and cardiometabolic health. Clinical evaluation relies primarily on GH stimulation testing and circulating insulin-like growth factor 1 (IGF-1), but these measures incompletely reflect downstream tissue-level consequences of impaired GH bioactivity. Metabolomic and lipidomic profiling provide systems-level approaches for characterizing these consequences. Evidence from experimental models and human studies implicates coordinated alterations in amino-acid turnover, mitochondrial and central energy metabolism, fatty-acid handling, and lipid remodeling, consistent with disrupted substrate exchange across GH-responsive tissues. These signatures are influenced by sex, developmental stage, adiposity, nutritional state, treatment exposure, and analytical platform, limiting the interpretation of individual metabolites as universal biomarkers. In this review, we integrate current metabolomic and lipidomic evidence with established GH biology, including temporal and sex-dependent signaling, tissue-specific metabolic actions, and responses to GH replacement. We further evaluate the potential of metabolic signatures for biological phenotyping, treatment-response assessment, and pharmacodynamic monitoring. Current evidence supports metabolomics and lipidomics as promising functional readouts of altered GH action, but not yet as validated diagnostic tools. Progress toward clinical translation will require standardized study designs, longitudinal sampling, sex- and development-aware analyses, harmonized analytical workflows, and independent validation in well-characterized cohorts.