Reduced fibroblast growth factor 21 and β-Klotho secretion in untreated congenital isolated GH deficiency

Increasing evidence suggests that the FGF-Klotho endocrine system and the somatotropic system (pituitary and extra-pituitary GH) may have important metabolic and immune relationships, thus contributing to the pathophysiology of aging-related disorders, including diabetes, atherosclerosis, and cancer. The status of these interactions in isolated GH deficiency (IGHD) is unknown. The objective of this study was to assess the response of both FGF21 and β-Klotho levels to a standard meal in a homogeneous group of adults with congenital untreated IGHD due to a homozygous mutation in the GHRH receptor gene.

In a cross-sectional study, we measured the levels of FGF21 and β-Klotho, before and 30, 60, 120, and 180 min after a standardized test meal in 20 (11 males) IGHD and 20 (11 males) age-matched controls. Areas under the curves (AUC) of FGF21 and β-Klotho were calculated.

Baseline levels of FGF21 were similar, but baseline levels of β-Klotho were lower in IGHD subjects. The IGHD individuals exhibited lower AUC for FGF21 and β-Klotho levels than control subjects. There was a positive correlation between IGF1 and β-Klotho levels in the pooled groups. No correlation was found between IGF1 and FGF21 levels.

Subjects with lifetime, untreated IGHD exhibit reduced FGF21 and β-Klotho levels response to a mixed meal. This difference may have consequences on metabolism and aging.