Growth hormone treatment for two years is safe and effective in adults with Prader-Willi syndrome
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.
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ABSTRACT: AimGrowth hormone (GH) treatment is a relatively new concept in adults and the knowledge of its long-term effects is limited. We studied ten men with Prader-Willi Syndrome (PWS) after more than five years of GH treatment.Methods Study participants underwent a detailed physical examination, including blood tests. Five had received GH since childhood and five had started GH as adults.ResultsThe total duration of GH treatment was 16±4 years in the childhood PWS group and 15±1 years in the adulthood PWS group. Their respective mean ages were 27±4 years and 44±4 years, mean heights were 178±11 cm and 156±5 cm and mean body mass indexes were 32.4±10.3 kg/m2 and 28.9±4.6 kg/m2. There were no differences in body composition between the groups and all lipids and insulin-like growth factor 1 were normal or close to normal. Four had well-controlled type 2 diabetes. The GH doses in the childhood and adulthood groups were 0.4mg and 0.3mg respectively.Conclusion Men with PWS who received GH treatment displayed positive effects on body composition independent of when the GH treatment had started. Only patients who gained weight developed diabetes. The duration of GH treatment should balance the benefits and observed side effects.This article is protected by copyright. All rights reserved.Acta Paediatrica 12/2014; DOI:10.1111/apa.12898 · 1.97 Impact Factor
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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 & Metabolism 06/2014; 99(9):jc20142059. DOI:10.1210/jc.2014-2059 · 6.31 Impact Factor
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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; 164(3). DOI:10.1002/ajmg.a.36355 · 2.30 Impact Factor