Histology of Skeletal Muscle in Adults with GH Deficiency: Comparison with Normal Muscle and Response to GH Treatment

Abstract

The histology of needle biopsy specimens of skeletal muscle from the vastus lateralis was quantitatively assessed in a group of adults with growth hormone (GH) deficiency, most of whom had hypopituitarism treated with conventional pituitary hormone replacement. The mean age of the 21 patients (16 males and 5 females) was 39 ± 2 (SEM). Comparisons were made with age-and sex-matched controls following six months double-blind, placebo-controlled treatment with recombinant human GH (rhGH) in the GH-deficient patients. Before treatment, needle muscle biopsies from patients with GH deficiency showed mean type I and II fibre areas of 5,153 ± 273 and 4,828 ± 312 µm² respectively, which did not differ from the controls (4,482 ± 306 and 4,699 ± 310 µm²). Percentages of type I fibres were similar in the two groups (47.2 ± 2.5% in GH deficiency and 45.3 ± 2.2% in controls). No difference in the variability of type I or II fibre areas was demonstrated between the groups. Correlations between the relative contribution to total fibre area by type I fibres (mean fibre area × percent) and maximal oxygen uptake (p = 0.006), and between type II fibres and quadriceps force (p = 0.035) were noted in GH-deficient adults before treatment. Following rhGH treatment, no change was noted in mean fibre areas, variability of fibre areas, or percentage of either fibre type. We conclude that in adults with GH deficiency: (a) no consistent histological evidence of myopathy was seen; (b) qualitatively, the muscle fibres function similarly to normal, and (c) rhGH treatment does not result in any detectable change in fibre areas or proportion.

Action of GH on skeletal muscle function: molecular and metabolic mechanisms

“…Studies of GH replacement up to 6 months have reported no significant change in muscle fibre composition in adults with GHD (Whitehead et al 1989, Cuneo et al 1992, Daugaard et al 1999. One of these studies reported an increase in muscle size and improvement in endurance capacity, but observed no change in the number of type I or II fibres (Cuneo et al 1992). It is unclear from this study whether the relationship between the improvement in endurance and in type I fibre size is associative or causal.…”

“…Most studies on adult subjects with GHD have reported no significant difference in fibretype distribution from matched normal subjects (Whitehead et al 1989, Cuneo et al 1992, Bottinelli et al 1997. A time-dependent relationship between the duration of GHD and fibre-type composition is unlikely from a comparison of findings between patients with childhood-onset and adult-onset GHD (Whitehead et al 1989, Cuneo et al 1992, Bottinelli et al 1997.…”

“…Daugaard et al (1999) found no relationship between IGF1 levels and MHC composition, suggesting that the severity of GHD does not influence MHC composition. Studies of GH replacement up to 6 months have reported no significant change in muscle fibre composition in adults with GHD (Whitehead et al 1989, Cuneo et al 1992, Daugaard et al 1999. One of these studies reported an increase in muscle size and improvement in endurance capacity, but observed no change in the number of type I or II fibres (Cuneo et al 1992).…”

The role of growth hormone in the regulation of the anaerobic energy system and physical function

“…Most studies in adult subjects with GHD have reported no significant difference in fibre type distribution from matched normal subjects (89)(90)(91). A time-dependent relationship between the duration of GHD and fibre type composition is unlikely from a comparison of findings between patients with childhood-onset and adult-onset GHD (89)(90)(91).…”

“…Daugaard et al found no relationship between IGFI levels and MHC composition, suggesting that the severity of GHD does not influence MHC composition (92). Studies of GH replacement up to 6 months have reported no significant change in muscle fibre composition in adults with GHD (90)(91)(92). One of these studies reported an increase in muscle size and improvement in endurance capacity, but observed no change in the number of type I or II fibres (90).…”