Endocrine Abstracts

Context: GH deficient (GHD) adults can experience fatigue which resolves with GH replacement. The precise basis of this is unclear. Suboptimal mitochondrial function has been demonstrated in several conditions in which fatigue is a prominent symptom. Phosphorus-31 magnetic resonance spectroscopy (31P-MRS) can measure maximal mitochondrial oxidative phosphorylation, an important parameter of mitochondrial function. We have adapted this technique to enable non-invasive measurement of muscle mitochondrial oxidative phosphorylation in vivo during dynamic muscle activity.

Objective: To characterise and compare in vivo skeletal muscle metabolism in age, gender and physical activity matched untreated GHD adults, treated GHD adults and healthy volunteers. We also compared the perception of fatigue using specific domains within Qol-AGHDA across the three groups.

Design: Twenty two untreated GHD adults, 23 treated GHD adults and 20 healthy volunteers were recruited at a tertiary University centre. All patients underwent assessment of muscle mitochondrial function (τ_1/2 PCr) using ³¹P-MRS. Fasting biochemical analyses and anthropometric measurements were obtained. All patients completed questionnaires on quality of life (QoL-AGHDA) and physical activity assessment (IPAQ).

Results: There was no difference in maximal mitochondrial function (P=0.53) and proton handling (P=0.30) of skeletal muscle between untreated GHD, treated GHD and healthy volunteers. There was no association between τ_1/2 PCr and serum IGF1 (r=−0.13, P=0.32). Untreated GHD adults complained of significantly increased fatigue and impaired QoL when compared to treated GHD adults and healthy controls (P=0.009, P=0.002). Untreated GHD patients had significantly lower IGF1 than both treated GHD and healthy volunteers (P<0.001).

Conclusions: Whilst untreated GHD adults experience fatigue compared to treated GHD adults and normal volunteers, they do not demonstrate persistent abnormalities in maximal mitochondrial oxidative function, anaerobic glycolysis nor proton clearance as assessed by 31P-MRS. This suggests a likely central component in the pathophysiology of fatigue in GH deficiency.

Declaration of funding: The 1st year of the study was funded by Pfizer Inc and the 2nd year by Merc Serono Inc. However, they were not involved in the design, conduct or analysis of the study.