Metabolomics: a tool for the diagnosis of GH deficiency and for monitoring GH replacement?

Abstract

The diagnostic value of insulin-like growth factor 1 (IGF1) for GH deficiency (GHD) in adults is not optimal. Molecular profiling could be used for biomarker discovery. The aim of this pilot study was to compare the serum metabolome between GHD patients and healthy controls, and identification of potential markers for diagnosis and/or for individual GH dosing. A total of ten patients with GHD, median age of 55 years and BMI of 27 kg/m2, were compared with ten healthy age- and gender-matched controls. The serum metabolic profiles were generated using gas chromatography-coupled mass spectroscopy on fasting samples taken in the morning from the controls and at baseline and during 6 months of GH replacement in the patients with GHD. The difference in low-molecular weight compounds (LMC) distinguished the healthy controls from GHD patients. Among 285 measured metabolites, 13 were identified as being most important in differentiating GHD patients from controls. Of these, 11 could not be structurally annotated but many were classified as lipids. The difference in the LMC pattern persisted despite normalisation of IGF1 following GH replacement. GH replacement increased the levels of specific fatty acid compounds and decreased the levels of certain amino acids. No metabolite changed in response to GH treatment, to the same extent as IGF1. The measurement of 285 metabolites resulted in a unique pattern in GHD, but changes in the metabolite patterns during GH treatment were limited. The utility of metabolomics to find new markers in GHD and GH replacement remains to be further elucidated.

Growth Hormone Deficiency in Prepubertal Children: Predictive Markers of Cardiovascular Disease

“…At present, only two studies have identified specific metabolic profiles in patients with GHD: one performed as a single-case study in a female adolescent with severe GHD and the second report in adults with GHD compared to healthy controls [58,59]. …”

“…The metabolome analysis has identified clear differences between the groups, mostly within the lipid class. During r-hGH replacement, major changes in amino and fatty acids occurred [59]. …”

“…Eleven of them were classified as lipids, including phospholipids, and 2 were identified as cysteine and glyceric acid. r-hGH replacement increased the levels of specific fatty acid compounds and decreased the levels of certain amino acids [59]. …”

“…Overall, these results highlight the importance of metabolomics and of proteomics in the identification of serum biomarkers of GH action in children with GHD and in defining the response to r-hGH treatment [59]. …”

A role for metabolomics in the antidoping toolbox?

“…Metabolomics has proven to be a highly suitable tool for studying the metabolism of living matter, including humans 41 . It has already been demonstrated to be suitable for studying the effects of hormone treatment on hormone deficient patients to evaluate their general metabolism and to understand whether there are adverse effects in the short or long term use of such substances 42,43 . Similarly, metabolomics might be employed to detect altered metabolism in athletes as a screening strategy in antidoping programs, pointing to those athletes who may have abnormal values for several metabolites due to plausible doping administration.…”