Article

Growth hormone treatment for two years is safe and effective in adults with Prader-Willi syndrome.

Centre for Rare Diseases, Department of Paediatrics, Aarhus University Hospital Skejby, DK-8200 Aarhus N, Denmark.
Growth hormone & IGF research: official journal of the Growth Hormone Research Society and the International IGF Research Society (Impact Factor: 2.35). 06/2011; 21(4):185-90. DOI: 10.1016/j.ghir.2011.05.002
Source: PubMed

ABSTRACT Prader-Willi syndrome (PWS) shares similarities with the growth hormone (GH) deficiency syndrome in regards to reduced lean body mass and increased fat mass and several short-term trials with GH treatment have demonstrated beneficial effects on body composition. The aim of the present study was to evaluate the effects and safety of two years of GH therapy in adults with PWS.
Forty-three adults (24 women) with genetically verified PWS were included. Blood samples, body composition as measured by computed tomography (CT) and dual-energy x-ray absorptiometry (DXA) were performed at baseline and during two years of continued GH treatment.
Thirty-nine patients completed treatment for two years. The GH dosage averaged 0.61 mg/day (range 0.2-1.6). Based upon CT, body composition improved at two years; thigh muscle volume increased 6.7 mL (3.7 to 9.7; P<0.001) whereas abdominal subcutaneous fat volume decreased by 53.3 mL (13.8 to 92.9; P=0.01). By DXA, lean body mass improved 2.8 kg (1.9 to 3.6; P<0.001), whereas fat mass decreased by 3.0 kg (1.1 to 4.8; P=0.003). Lung function as evaluated by peak expiratory flow increased 12% (p<0.001) - indicating improved muscle function. Adverse effects were few. Fifteen out of 39 patients had diabetes (DM; n=4) or impaired glucose tolerance (IGT; n=11) prior to GH treatment. Among the 11 patients with IGT, three reverted to normal glucose tolerance, while three progressed to overt DM at two years of GH treatment.
The known beneficial effects of GH treatment upon body composition in PWS are maintained during two years continuous treatment. With appropriate control, GH is a safe treatment option in adults with PWS.

0 Bookmarks
 · 
112 Views
  • [Show abstract] [Hide abstract]
    ABSTRACT: Context Visceral adipose tissue (VAT) is established as a risk factor for type 2 diabetes and cardiovascular disease, but the radiation exposure and cost of computed tomography (CT) measurements limits its daily clinical use. Objective The main aim of this study was to compare the degree of agreement between VAT measurements by a new dual-energy X-ray absorptiometry (DXA) application and one of the standard methods - CT, in a population of patients with Prader-Willi syndrome (PWS) before and after growth hormone (GH) treatment. Furthermore, we tested if VAT estimations by these two methods are equivalent in assessing metabolic risk in this population. Design and Patients Data from the Norwegian population of a multicenter study in adults with genetically proven PWS was used. Subjects with complete anthropometry, biochemical and imagistic measurements at all study visits (baseline, and after 12 and 24 months of GH treatment) (n=14, men 6) were included. VAT was quantified both using CT scans (GE Lightspeed 16 Pro) of the abdomen at L2-L3 level and a total body DXA scan (GE Healthcare Lunar Prodigy). Results VAT DXA was strongly associated with VAT CT at baseline (r=0.97) and after 12 (r=0.90) and 24 months (r=0.89) of GH treatment (all P<0.001). We found moderate to strong positive correlations between VAT by both methods, and blood pressure, weight, BMI, waist circumference, glucose metabolism and other fat depots (arms, legs, android, trunk, total body), but no association with age, gender, blood lipids and IGF-I. Adiponectin was negatively associated with the amount of VAT. At baseline, the highest correlation with HOMA-IR was found for VAT DXA (r=0.76, P=0.001), and VAT CT (r=0.75, P=0.002) respectively. Conclusion VAT can be accurately estimated by DXA, in patients with PWS, and might contribute to the assessment of the metabolic risk.
    Journal of Clinical Endocrinology &amp Metabolism 06/2014; · 6.31 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Long-term treatment with growth hormone (GH) in patients with Prader-Willi syndrome (PWS) improves not only height velocity, height standard deviation score, and final height, but also the degree of obesity and body composition abnormalities. Anecdotally, PWS patients tend to suffer from severe obesity and its complications after cessation of GH therapy. However, there have been no studies to investigate changes in body mass index (BMI) and adipose tissue distribution after cessation of GH therapy in young PWS patients. Therefore, we investigated changes in the BMI-standard deviation score (SDS) and adipose tissue distribution after cessation of GH therapy in PWS patients. We evaluated 14 PWS patients. BMI-SDS was calculated at 0, 6, 12, 18, and 24 months before and after cessation of GH treatment. We also evaluated subcutaneous adipose tissue (SAT) (cm(2) ) and visceral adipose tissue (VAT) (cm(2) ) area in 8 of the 14 study patients with single slice abdominal computed tomography at the level of the umbilicus. The BMI-SDS significantly increased at 6, 12, 18, and 24 months after cessation of GH therapy (P = 0.039, P = 0.008, P = 0.003, P = 0.003, respectively). There was a tendency toward increases in VAT at 12 and 24 months after cessation of GH therapy, but the increases did not reach statistical significance (P = 0.062, P = 0.125, respectively). Therefore, cessation of GH therapy in PWS patients worsened BMI. To maintain good body composition and prevent complications of obesity, long-term use of GH in adult PWS patients may be advisable. © 2014 Wiley Periodicals, Inc.
    American Journal of Medical Genetics Part A 01/2014; · 2.30 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: To investigate glucose homeostasis in relation to body mass index (BMI) in adults with PWS before and after GH therapy. We prospectively investigated the effects of a 12-month GH treatment on body composition and glucose homeostasis in relation to BMI in 39 adults, mean (±SD) age=28.6 (6.5) years with genetically verified PWS. We compared the results for different BMI categories (<25kg/m(2); 25-30kg/m(2); >30kg/m(2)) and performed a regression analysis to detect predictors for homeostasis model of assessment-insulin resistance (HOMA-IR). The baseline HOMA-IR was higher, with BMI of >30kg/m(2). Our main findings were as follows: i) GH treatment (mean final dose, 0.6 (0.25) mg) was associated with small increases in fasting p-glucose, 2-h p-glucose by oral glucose load tolerance test, HOMA-IR and lean mass, and a reduction in fat mass. ii) Whereas the baseline HOMA-IR was associated with increased BMI (>30kg/m(2)), we found no differences in HOMA-IR among the BMI categories after 12months of GH. iii) Stepwise linear regression identified the triglyceride level as the strongest predictor of HOMA-IR at baseline, whereas an increase in VAT was the strongest predictor of the increase in HOMA-IR after therapy. GH treatment for 12months in adults with PWS resulted in an increase in HOMA-IR, irrespective of BMI, confirming that control of HbA1c is essential during GH treatment in PWS.
    Growth hormone & IGF research: official journal of the Growth Hormone Research Society and the International IGF Research Society 12/2013; · 2.35 Impact Factor