Identification of New Biomarkers of Low-Dose GH Replacement Therapy in GH-Deficient Patients

Abstract

GH secretion peaks at puberty and continues to be secreted in adulthood, albeit at a declining rate. Profound GH deficiency (GHD) in adults with pituitary disease is associated with symptoms that improve with GH substitution, but it is important to tailor the GH dose to avoid overtreatment. Measurement of serum IGF-I levels is an important clinical tool in this regard, but it is well recognized that some patients receiving GH treatment do not show an increase in IGF-I. The objective of the study was to identify novel serum biomarkers of GH treatment in adults with GHD. Eight patients with profound GHD as a consequence of a pituitary adenoma or its treatment were evaluated before and 3 months after GH replacement therapy (0.2-0.4 mg/d). Serum proteomic changes were studied using two-dimensional gel electrophoresis and mass spectrometry. Protein profiles were analyzed and compared in serum samples obtained before and after GH treatment. The levels of six serum protein spots were significantly altered after GH substitution. These proteins were identified as five isoforms of haptoglobin (decreased in posttreatment samples) and one isoform of apolipoprotein A-I (increased in posttreatment samples). Importantly, changes in the levels of the identified proteins were associated with decreases in fat mass and increases in lean mass in all patients. These results were independent of serum IGF-I levels. Evaluation of the identified proteins provides a novel alternative to traditional markers of GH status, such as serum IGF-I levels, to assess GH therapy in GH deficient adults.