Endocrine Abstracts

Introduction: Even though fatigue is a common complaint in GH deficiency (GHD), its pathophysiology remains poorly understood. Fatigue can reflect central or peripheral disease processes. 31-Phosphorus magnetic resonance spectroscopy (³¹P-MRS) is a non-invasive technique used to measure skeletal muscle bioenergetics in vivo. Specifically, mitochondrial oxidative phosphorylation and proton efflux can be measured dynamically and in ‘real time’. The aim of this study was to examine the biology of fatigue in GHD using surrogates of central and peripheral fatigue i.e. with a self reported questionnaire and ³¹P-MRS respectively.

Methods: In this cross-sectional study, we compared skeletal muscle bioenergetics using ³¹P-MRS in three groups: untreated GHD, treated GHD and healthy controls (age and sex matched). Resting metabolites and parameters of oxidative phosphorylation-τ_1/2PCr and proton efflux were calculated during a validated exercise protocol. Blood was taken to ensure appropriate hormone replacement. Body composition was assessed using bio-impedance and a validated QoL questionnaire (AGHDA) completed. One-way ANOVA was used for comparisons (Minitab v16).

Results: Patient age and sex were comparable in the three groups (mean age 27.9, 29.8 and 31.0 years; P=0.53) but % body fat was greater in the GHD patients compared to controls (P=0.04). No significant differences in resting metabolite parameters (Pi, PCr and pH) were detected. Importantly, there was no significant difference in either τ_1/2 PCr (P=0.56) nor proton efflux (P=0.44) despite significant differences in perceptions of fatigue and AGHDA-QoL (P=0.002).

Conclusions: Untreated GHD adults do not express an abnormal ‘bioenergetic footprint’ compared to either treated GHD adults or healthy controls. This suggests that fatigue in GHD does not reflect abnormal mitochondrial oxidative phosphorylation nor delayed proton efflux. The perception of fatigue may, therefore, arise from dysregulation of the neuroendocrine system rather than abnormal muscle function; i.e. ‘central fatigue rather than peripheral fatigue’.