ESPE2022 Poster Category 1 GH and IGFs (27 abstracts)
Background and Objectives: In recent years, a growing number of studies investigated the profile of serum metabolomics in health and disease. These studies have led to the discovery of novel biological biomarkers and causative agents for a variety of medical conditions. Here, we focused on profiling serum metabolites of children diagnosed with growth hormone deficiency (GHD).
Methods: We conducted a prospective study and collected serum samples from children aged 3-18 years arriving to a glucagon or arginine growth hormone stimulation test (GHST). Children with genetic syndromes or chromosomal abnormalities, systemic illness or end-stage renal disease were excluded from participation. An inadequate response to GHST was defined as peak serum GH concentration of 7.5 ng/ml or less. GHD diagnosis was made after two separate stimulation tests demonstrating inadequate GH response. We performed metabolic profiling analysis using liquid chromatography-mass spectrometry (LC-MS) that measured the levels of 951 circulating metabolites (including 280 polar metabolites and 671 lipids) in the serum samples. We compared the levels of these metabolites between cases and controls, and estimated the P-values using the two-sided Mann–Whitney U test. False Discovery Rate (FDR) was employed at the rate of 0.1.
Results: Serum samples of 68 children who were recruited to the study between November 2017 and March 2021 were analyzed. Mean age was 8.43 ± 3.68 years (median 8.22 years, IQR [5.19- 11.62]), 45 (66.2%) were boys. Twenty-five (36.8%) children were diagnosed as having GHD and 43 (63.2%) children served as controls. There were no significant differences between the groups in age, sex, tanner stage, height and weight measurements at test initiation and the type of GHST preformed. Overall, 20 polar metabolites and 76 lipids were significantly different between the groups (P<0.05). Metabolites measured higher in children with GHD included Myo-Inositol, Creatine, N, N-Dimethylglycine and Pantothenate and metabolites with higher levels in the control group included Heptanoic acid and N-Octanoylglycine. However, following FDR correction, only one lipid metabolite, phosphatidylserine (PS) (40:3), which was higher in children with GHD, remained significant.
Conclusion: Unique metabolic profiles in children with GHD offer an opportunity for development of novel diagnostic tests and identification of altered biological pathways. We found 96 plasma metabolites which were significantly different in children diagnosed with GHD compared to controls. Additional and larger scale studies are needed to identify the potential utility of the serum metabolic profiles as a diagnostic tool for GHD.
15 Sep 2022 - 17 Sep 2022