Body composition and quality of life in adults with growth hormone deficiency; effects of low-dose growth hormone replacement

OBJECTIVE Adult growth hormone deficiency (AGHD) is characterized by abnorm alities in body composition and a poor perceived quality of life (QoL). Wei ght-based high-dose growth hormone replacement (GHR) results in improvement s in body composition and QoL in AGHD. However, a high patient percentage r eported side-effects on high-dose GHR resulting in a high rate of patient w ithdrawal from growth hormone (GH) treatment. High-dose GH therapy also lea ds to supraphysiological serum insulin-like growth factor-I (IGF-I) concent rations that have been associated with breast and prostate cancer, raising major concerns over the use of such high-dose GH regimen in AGHD. The aim o f this study was to assess the effects of low-dose growth hormone replaceme nt (GHR) on body composition and QoL as early as 1 and 3 months. STUDY DESIGN A prospective, open treatment design study to determine the ea rly effects of low-dose GH administration on body composition and QoL. GH w as initiated at a daily dose of 0.4-0.5 IU, and titrated up to achieve and maintain IGF-I standard deviation score (IGF-I SDS) between the median and upper end of the age-related reference range. PATIENTS Forty-six, post-pituitary surgery, severe AGHD patients (22 women) , defined as peak GH response <9 mU/I to provocative testing. The mean age was 50.4years (range 26-72). Forty-three patients required additional pitui tary replacement hormones following pituitary surgery and were on optimal d oses at recruitment. MEASUREMENTS Body composition and QoL were assessed prior to GHR and subseq uently at 1 and 3 months after initiating GHR. Body mass index (BMI) and wa ist hip ratio (WHR) were calculated from measurements of height, weight, an d waist and hip circumference, respectively. Bioelectrical impedance analys is (BIA) was used to determine body fat and lean body mass. QoL was assesse d using the disease-specific 'QoL-assessment of growth hormone deficiency i n adults (QoL-AGHDA)' questionnaire. Serum IGF-I was measured at each visit to assess the adequacy of GHR. RESULTS IGF-I and IGF-I SDS increased significantly at 1 and 3 months (P < 0.001) after commencing GHR. The increase in IGF-I (P < 0.05) and IGF-I SDS (P < 0.01) was significant between 1 and 3 months in the absence of any si gnificant increase in GH dose (P = ns) during this period. Eighty-five per cent of patients achieved IGF-I SDS levels between median and upper end of the age-related reference range after 3 months of GHR, and no side-effects were reported during this period. There was a significant reduction in body fat percentage (BFP) from 36.1 +/- 9.1% at baseline to 34.9 +/- 9.3% (P < 0.01) at 1 month and 34.1 +/- 9.2% (P < 0.001) at 3 months. Body fat mass ( BFM) reduced from 32.8 +/- 13.6 kg at baseline to 31.9 +/- 13.9 kg at 1 mon th (P < 0.05) and 31.1 +/- 13.6 kg at 3 months (P < 0.001). These changes i n BFP and BFM occurred in the absence of any significant change in BMI and WHR (P = ns). Lean body mass (LBM) was 55.9 +/- 11.1 kg at baseline and inc reased to 57.1 +/- 11.3 kg after 1 month (P < 0.01) and to 57.6 +/- 11.5 kg (P < 0.001) after 3 months of GHR. Significant improvement was observed in the perceived QoL with the AGHD assessment scores reducing from 13.3 +/- 6 .4 to 11.5 +/- 6.6 within 1 month (P < 0.01) and 10.0 +/- 6.6 at 3 months ( P < 0.001). There was no significant correlation between improvement in QoL and changes in body fat percentage (r = 0.01 at 1 month and r = 0.12 at 3 months, P = ns) or IGF-I levels (r = 0.04 and r = 0.003, P = ns at 1 and 3 months, respectively). The improvement in body composition and QoL was sign ificant between 1 and 3 months. CONCLUSIONS Low-dose GHR improves body composition and QoL as early as 1 mo nth after commencement and the beneficial effects continue at 3 months. Mos t importantly, these changes occur in the absence of side-effects. We there fore suggest the use of low-dose GH therapy, maintaining IGF-I between the median and upper end of the age-related reference range, for the treatment of AGHD.