Abstract
The impact of GH on functional performance in GH-deficient adults is not well understood. To investigate the effects of GH on skeletal muscle, physical, and functional capacity, we randomized 28 GH-deficient adults to receive 3 months of recombinant human GH [rhGH: somatotropin, 6.25 μg/kg lean body mass (LBM) for 1 month, 12.5 μg/kg LBM thereafter] in a double-blind placebo-controlled crossover trial. We measured muscle fiber type, size, and insulin-like growth factor I messenger RNA, aerobic capacity [maximal oxygen uptake (VO2max), ventilation threshold (VeT)], isokinetic strength, oxygen-cost-of-walking at normal and fast speeds, and fatigue determined by the profile of mood states questionnaire. As expected, GH treatment decreased body fat, increased LBM, increased muscle fiber size, and increased muscle insulin-like growth factor-I messenger RNA 5-fold; however, muscle strength remained unchanged. At baseline, VeT occurred at a high percentage of maximal VO2max (73.3% ± 2.6) because of low VO2max (1.74 ± 0.1 L/min or 20.7 ± 1.3 mL/kg·min). Walking required high oxygen consumptions representing from 83 ± 4% of VeT at normal speeds to 120 ± 5% of VeT at fast speeds. After rhGH, there was a significant (P = 0.03) increase in VeT (18%), compared with placebo. This was paralleled by a nonsignificant rise in VO2max. Functionally, rhGH treatment decreased the oxygen cost of walking, relative to VeT, at normal (14% decrease, P = 0.019) and fast (21% decrease, P = 0.004) SPW speeds. A 3-variable model (baseline fast SPW speed, VeT/VO2max, and VeT) accounted for 39% of the variance of change in self-reported fatigue. These data indicate that GH-deficient adults require a high fraction of VeT for daily activities, explaining the perception of increased fatigue and impaired physical performance. The actions of rhGH on muscle fiber size translate into physiological improvement in submaximal aerobic capacity and result in functional improvement in walking ability but do not necessarily alter strength. Thus, measures of effort-independent submaximal aerobic performance provide novel objective determinants of functional impairment and fatigue and can be used to evaluate and predict response to GH treatment.