Long-term growth hormone benefits confirmed in Prader–Willi syndrome

By Eleanor McDermid
J Clin Endocrinol Metab 2017; Advance online publication
31 March 2017

medwireNews: Analysis of the KIGS database confirms the beneficial effects of recombinant human growth hormone (rhGH) on height and weight in children with Prader–Willi syndrome (PWS).

Nienke Bakker (Dutch Growth Research Foundation, Rotterdam) and colleagues studied two groups of PWS patients: 522 who received at least 3 years of rhGH treatment during prepubescence and 173 who were treated during adolescence until near adult height.

In the younger children, height standard deviation score (SDS) improved markedly, from –2.05 at treatment initiation, when they were aged an average of 4.4 years, to –0.31 after 3 years.

The adolescents began treatment at an average age of 8.2 years, and made good initial progress, with their average height SDS improving from –2.14 to –0.22 at the start of puberty. However, this then declined, despite continued treatment, resulting in a final height SDS of –1.19.

Nevertheless, this was a significant improvement from baseline and, the team says, equated to “acceptable” near-adult heights of 170.1 cm in boys and 155.8 cm in girls.

The researchers attribute the decreased treatment effect during puberty to the reduced pubertal growth spurt seen in PWS patients irrespective of treatment, due to delayed development after Tanner stage 3. Although data are lacking, they suggest that “by adequate sex hormone substitution some additional height gain could be expected.”

Treatment with rhGH had the anticipated effects on body mass index (BMI), with the average SDS remaining below +2.0, which Bakker and team say is “in contrast to the natural course of increasing obesity in children with PWS.”

However, they observe that the average weekly rhGH dose used was 0.22 mg/kg – well short of the recommended 1 mg/kg, suggesting that a higher dose might further improve BMI outcomes, and they note that earlier initiation of rhGH could stabilise BMI at a lower level.

“Moreover, early initiation of GH treatment has also shown its benefits in motor and mental development in young children with PWS,” they write in The Journal of Clinical Endocrinology & Metabolism.

Of the total 2332 PWS patients in the database, 545 had reported adverse events, including 174 serious adverse events. Scoliosis was by far the most frequent adverse event, and other known side effects of PWS, such as cryptorchidism, sleep apnoea and psychiatric disorders, were also common.

Twelve children died, of causes including gastric perforation, pneumonia and accident. The researchers say the reported annual death rate “seems low compared to the high annual mortality rate of 3% in untreated PWS patients.”

But they stress that “safety issues, such as diabetes, sleep-related breathing disorders, gastric problems and infections, should be closely monitored in children with PWS, with and without GH treatment.”

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