Measures of submaximal aerobic performance evaluate and predict functionalresponse to growth hormone (GH) treatment in GH-deficient adults

The impact of GH on functional performance in GH-deficient adults is not we ll understood. To investigate the effects of GH on skeletal muscle, physica l, and functional capacity, we randomized 28 GH-deficient adults to receive 3 months of recombinant human GH [rhGH: somatotropin, 6.25 mu g/kg lean bo dy mass (LBM) for 1 month, 12.5 mu g/kg LBM thereafter ] in a double-blind placebo-controlled crossover trial. We measured muscle fiber type, size, an d insulin-like growth factor I messenger RNA, aerobic capacity [maximal oxy gen uptake (VO(2)max), ventilation threshold (VeT)], isokinetic strength, o xygen-cost-of-walking at normal and fast speeds, and fatigue determined by the profile of mood states questionnaire. As expected, GH treatment decreas ed body fat, increased LBM, increased muscle fiber size, and increased musc le insulin-like growth factor-I messenger RNA 5-fold; however, muscle stren gth remained unchanged. At baseline, VeT occurred at a high percentage of m aximal VO(2)max (73.3% +/- 2.6) because of low VO(2)max (1.74 +/- 0.1 L/min or 20.7 +/- 1.3 mL/kg.m). Walking required high oxygen consumptions repres enting 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 V O(2)max. Functionally, rhGH treatment decreased the oxygen cost of walking, relative to VeT, at normal (14% decrease, P = 0.019) and fast (21% decreas e, P = 0.004) SPW speeds. A 3-variable model (baseline fast SPW speed, VeT/ VO(2)max, and VeT) accounted for 39% of the variance of change in self-repo rted fatigue. These data indicate that GH-deficient adults require a high f raction of VeT for daily activities, explaining the perception of increased fatigue and impaired physical performance. The actions of rhGH on muscle f iber size translate into physiological improvement in submaximal aerobic ca pacity and result in functional improvement in walking ability but do not n ecessarily alter strength. Thus, measures of effort-independent submaximal aerobic performance provide novel objective determinants of functional impa irment and fatigue and can he used to evaluate and predict response to GH t reatment.