Interdependence of lean body mass and total body water, but not quality of life measures, during low dose GH replacement in GH-deficient adults

Abstract

Lean body mass (LBM) and total body water (TBW) are reduced in GH-deficient (GHD) adults and alter with GH replacement. Whether these parameters are interdependent and whether alterations in their homeostasis contribute to the perceived quality of life (QOL) deficit in GHD remains unclear. In this study, IGF-I, body composition by whole-body dual-energy X-ray absorptiometry, TBW by deuterium dilution (D 2 O) and two validated QOL instruments -psychological general well-being schedule (PGWB, generic, 6 domains; lower score worse QOL) and assessment of GH deficiency in adults (AGHDA, disease orientated; higher score worse QOL) were studied at baseline and after 3 and 6 months of GH replacement in thirty GHD adults. Patients with diabetes insipidus, and cardiac and renal failure were excluded. Median age-adjusted IGF-I standard deviation score increased from 2 3.40 (26.40 to 2 1.60) to 2 0.2 (2 1.88 to 0.78) (P , 0.0001) at a median daily GH dose of 0.4 mg. During treatment, LBM increased from 47.4^10.7 kg at baseline to 49.5^10.8 kg at 6 months (P ¼ 0.0008), and fat mass decreased from 28.0^12.1 kg at baseline to 27.2^12.6 kg at 6 months (P ¼ 0.0004). A non-significant trend towards an increase in TBW was observed (mean 1.7 kg, P ¼ 0.08). The PGWB score increased from 62.9^20.6 to 73.7^21.7 (P ¼ 0.0006). The AGHDA score decreased from 13.7^7.3 to 8.75^7.75 (P ¼ 0.0002). At each time point, a linear correlation between LBM and TBW was demonstrated, defined by TBW ¼ (0.972 £ LBM)-10.6. However, only a weakly positive correlation existed between the percentage changes in these variables (R ¼ 0.40, P ¼ 0.04). No correlations were demonstrated between QOL measures and body composition. The change in LBM with physiological GH replacement correlates weakly with change in TBW, therefore factors other than TBW may also contribute to the LBM changes. Improved QOL with GH replacement is not explained by favourable changes in body composition.European Journal of Endocrinology 153 661-668

Models to predict changes in serum IGF1 and body composition in response to GH replacement therapy in GH-deficient adults

“…In our models, we clearly observed that a patient could be a GR in one parameter and a PR in the other, indicating a need for different prediction models for each studied outcome. This is in agreement with previous observations showing poor correlations between improvement in QoL and biochemical, metabolic or BC changes during adult GH replacement therapy (44)(45)(46)(47).…”

“…Impairment in QoL is, however, a prominent feature of adult GHD and often the main reason for initiating GH replacement (37). We did not include QoL as an end point because the patients' subjective perception concerning QoL was likely to be multifactorial in origin (44), and previous studies had found treatment response in QoL to be proportional to the baseline deviation from normality (45,46). In our models, we clearly observed that a patient could be a GR in one parameter and a PR in the other, indicating a need for different prediction models for each studied outcome.…”

Health-related quality of life and IGF-1 in GH-deficient adult patients on GH replacement therapy: analysis of the German KIMS data and the Study of Health in Pomerania

“…Moreover, studies investigating HRQoL and IGF-1 in patients with acromegaly confirmed our lack of association between IGF-1 levels and HRQoL assessment (27,28). We conclude that the improvement of HRQoL in GHD patients seems to be a complex mechanism that cannot be simply reflected by IGF-1 values or favourable changes in body composition for example (29). We do not know the specific reasons of these findings.…”

Heterogeneity in responsiveness of perceived quality of life to body composition changes between adult- and childhood-onset Japanese hypopituitary adults with GH deficiency during GH replacement

“…Fat mass is one of the most responsive external markers of the effects of GH in patients with GHD. Nevertheless, no relationship between changes in QoL and changes in fat mass, lean body mass, or IGF-I has been found in a variety of studies (11,18,19), except one which reported a significant correlation between body composition change as determined by bioelectrical impedance analysis and change in QoL score as measured with the disease-specific questionnaire, Quality of LifeAssessment of GHD in Adults (QoL-AGHDA) (20). Here, using DXA, we found significant associations between changes in general health and physical functioning subscales and fat mass change, with the trend being more consistent in AO than CO patients.…”