High-Performance Liquid Chromatography–Mass Spectrometry–based Metabolic Profiling of Adult Growth Hormone Deficiency

Abstract

Context: Patients with adult growth hormone deficiency (AGHD) are at increased risk of metabolic syndrome. Metabolic profiles in AGHD patients have been insufficiently evaluated. Objective: This work aims to explore serum metabolite profiles by metabolomics analysis and assess potential metabolites associated with recombinant human growth hormone (rhGH) treatment. Methods: Thirty-one AGHD patients and 31 healthy controls were enrolled. Untargeted ultra-performance liquid chromatography–coupled mass spectroscopy was conducted in all patients and controls at baseline and during 12 months of rhGH treatment in 11 AGHD patients. Data were processed by principal component analysis, variable importance in projection scoring, orthogonal partial least squares–discriminant analysis, and MetaboAnalyst 5.0. We further explored the associations between metabolites and clinical parameters. Results: Metabolomics indicated a distinct metabolic pattern between AGHD patients and healthy controls. The perturbed pathways mainly include the biosynthesis of unsaturated fatty acids, sphingolipid metabolism, glycerophospholipid metabolism, fatty acid elongation, degradation, and biosynthesis. rhGH treatment increased the levels of specific glycerophospholipids compounds and reduced fatty acid ester compounds. Significant correlations existed between the 40 identified metabolites and insulin-like growth factor-1 SD score (IGF-1 SDS), body composition, and glucose and lipid metabolism plasma markers. During rhGH treatment, there was a statistically significant negative correlation between deoxycholic acid glycine conjugate and waist-to-hip ratio, while a statistically significant positive correlation existed between decanoylcarnitine and serum low-density lipoprotein levels. Conclusion: AGHD patients have unique metabolomic profiles. rhGH treatment alters the serum levels of several fatty acid compounds/amino acids, which may contribute to the improvement of metabolic status in AGHD patients.