Visceral adipose tissue increases shortly after the cessation of GH therapy in adults with Prader-Willi syndrome

Abstract

GH therapy in pediatric patients with Prader-Willi syndrome (PWS) improves body composition, but discontinuation of GH after achieving adult height has been implicated in its deterioration. Although there is evidence for the deleterious effects of visceral adipose tissue (VAT) rather than subcutaneous adipose tissue (SAT) on the development of obesity-related complications, the effects of GH discontinuation on fat distribution in adults with PWS has not been fully investigated. Therefore, we utilized dual-energy X-ray absorptiometry (DEXA) and abdominal computed tomography (CT) to compare the fat distribution between before and 6 months or 12 months after the cessation of GH therapy in 7 adult PWS patients. GH therapy was initiated at a mean age of 4.1 ± 1.4 years and discontinued at a mean age of 18.9 ± 1.8 years. Serum IGF-1 levels were decreased by discontinuation of GH therapy. Fat mass was significantly increased 6 and 12 months after GH cessation, whereas muscle mass and bone mineral density were unchanged during both study periods. Abdominal CT analysis revealed that elevations in fat mass were due to increases in VAT rather than SAT. Circulating low-density lipoprotein (LDL) cholesterol levels were significantly elevated 6 months after GH cessation. In conclusion, discontinuation of GH therapy caused rapid increases in visceral adipose tissue and LDL cholesterol levels. These findings indicate that continuation of GH therapy may be a therapeutic option to maintain body composition; however, further studies regarding the long-term benefits and adverse effects of GH therapy in adults with PWS are required.

Time for a general approval of growth hormone treatment in adults with Prader–Willi syndrome

“…The beneficial effect of GH on body composition has also been proven indirectly by the observation of impaired body composition after GH treatment was discontinued. Thus, 12 months of discontinuation of GH resulted in a 22% increase in body fat in young adults [12] and to an increase in visceral adipose tissue in adults from 25.2 ± 14.5 to 48.0 ± 26.1 cm 2 (p = 0.024) [13]. In line with these findings, motor skills were impaired 6 months after GH treatment was discontinued [14].…”

The use of growth hormone therapy in adults with Prader‐Willi syndrome: A systematic review

“…BMI was included in 16 of the 18 papers discussing body composition. In 2 papers, there was a statistically significant increase in BMI after discontinuation of GH treatment 33,40 . Koizumi et al (2018) looked at the effects of discontinuation of GH treatment on body composition of PWS patients, and determined that BMI increased and LBM decreased as a result of the change 40 .…”

“…Two studies 40,41 demonstrated improvements in cholesterol levels, with reduced LDL and increased HDL cholesterol, whilst two other studies did not 32,42 . Two studies reported increased cardiorespiratory exercise capacity 37,38 .…”

Early start of growth hormone is associated with positive effects on auxology and metabolism in Prader-Willi-syndrome

“…Therefore, it is imperative that future studies determine whether the observed effects persist into puberty and adulthood and whether the cessation at this point leads to a deterioration of metabolic parameters and body composition. Koizumi et al reported an increase in LDL and visceral body fat 6 months after cessation of GHT in adults with PWS [ 54 ]. Kuppens et al [ 55 ] also described increases in fat mass when GHT was discontinued in young adults and therefore suggested there were potential benefits in continuing GHT even after adult height is reached.…”