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Title: The role of skeletal muscle energetics in the symptoms and metabolic characteristics of growth hormone deficiency and vitamin D deficiency :a functional MRS approach
Authors: Sinha, Akash
Issue Date: 2013
Publisher: Newcastle University
Abstract: Both growth hormone deficient (GHD) and vitamin D deficient adults complain of fatigue. Suboptimal skeletal muscle mitochondrial function has been implicated in several disorders where fatigue is a prominent feature. I examined in vivo dynamic skeletal muscle metabolism in GHD and vitamin D deficient adults using a non-invasive tool called phosphorus-31 magnetic resonance spectroscopy (31P MRS). 31P MRS can quantify abnormalities in metabolic work-cost relationship during exercise. In the first study, skeletal muscle metabolism was assessed in age, gender and physical activity matched untreated GHD adults, GH treated GHD adults and healthy volunteers. Fatigue perception was compared across the 3 groups using specific domains within a validated quality of life questionnaire (QoL-AGHDA). Whilst untreated GHD adults experienced more fatigue compared to treated GHD adults and normal volunteers, they did not demonstrate any perturbations in peripheral skeletal muscle metabolism as determined by 31P MRS: maximal mitochondrial oxidative function, anaerobic glycolysis and proton clearance. In the second study, the effect of cholecalciferol therapy on skeletal muscle mitochondrial function in vitamin D deficient adults who had presented to their local primary care team with fatigue was examined. 31P MRS assessments were undertaken in 12 symptomatic, severely vitamin D deficient subjects before and after treatment with cholecalciferol. Cholecalciferol therapy was found to augment skeletal muscle mitochondrial oxidative phosphorylation in these individuals. To summarise, I have examined dynamic skeletal muscle metabolism in two common endocrine disorders with contrasting results. There was no detectable perturbation in skeletal muscle metabolism in untreated GHD patients when compared to both matched GH replaced GHD patients and healthy controls. On the other hand, I have found that maximal mitochondrial function is improved and altered by vitamin D repletion in symptomatic vitamin D deficient adults, thereby suggesting a peripheral mechanism for fatigue in vitamin D deficiency. This is the first time that a link has been identified between vitamin D and the mitochondria in human skeletal muscle using 31P MRS.
Description: PhD Thesis
Appears in Collections:Institute of Genetic Medicine

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