Effects of recombinant human growth hormone (rhGH) on impairment and functional capacity in adults with growth hormone deficiency (GHD).
Published: 2005
Language: eng
Number of pages: 263
Description: The availability of recombinant human growth hormone (rhGH) has provided a treatment for adults with GH deficiency (GHD). However, the functional impact of rhGH therapy in adults with GHD is unknown. To investigate the effects of rhGH on physical impairments, functional disabilities, and quality of life we randomized 28 adults (18--68 yrs) with GHD to receive 3 months of rhGH (somatropin, 12.5 mug/kgLBM) or placebo in a double-blind, placebo-controlled cross-over trial. Impairment was examined at the tissue level as muscle fiber type, size and insulin-like growth factor-I mRNA (IGF-I mRNA), and at the whole body level as circulating concentrations of IGF-I and IGFBP1&3, muscular (strength and local muscular endurance) and aerobic (maximal oxygen uptake: VO2max and ventilation threshold: VeT) performance. Functional ability was assessed using both actual performance (self-paced walking speed), and self-report measures of health status, mood states and level of habitual physical activity.We demonstrate that alterations in the GH/IGF-I axis have profound effects on adults with untreated GHD resulting in multiple impairments. The functional impact of these impairments manifests as reduced physical, social and emotional function, resulting in poorer health-related quality of life than normal healthy controls. Adults with untreated GHD require a higher fraction of VeT for daily activities, suggesting that it is diminished aerobic capacity and not reduced muscle strength that influences their increased perception of fatigue and poorer health. Treatment with rhGH decreased body fat and increased lean body mass, muscle fiber size, and muscle IGF-I mRNA (5-fold), however muscle strength remained unchanged. VeT increased significantly with a parallel but non-significant rise in VO2max following rhGH but not placebo. Functionally, this translates into a decreased fraction of VeT required for activities of daily living, which may decrease the sense of fatigue experienced by rhGH-treated adults with GHD. Baseline walking speed, VeT/VO2max and VeT accounted for 39% of the variance of change in self-reported fatigue following rhGH. These data support the hypothesis that fatigue and VeT are intimately linked. In conclusion, measures of submaximal aerobic performance should be used as objective markers of functional impairment and fatigue to evaluate and predict response to rhGH therapy in adults with GHD.
Notes: Source: Dissertation Abstracts International, Volume: 66-10, Section: B, page: 5318.

Thesis (Ph.D.)--University of Toronto, 2005.

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