A level of growth hormone deficiency is present in nearly all individuals with PWS, so growth hormone therapy has been widely used internationally as a treatment for PWS since the year 2000. The primary benefit of treatment is not the normalisation of height which occurs, but the significant changes to body composition (increased lean body mass and reduced fat mass), with parents observing dramatic changes in strength and activity levels. In conjunction with an appropriate diet and exercise, “GHT is a potent force for counteracting the clinical course of obesity in Prader-Willi syndrome.” (Bakker et al 2013.) Studies have also shown improvements in bone mineral density, motor development, cognitive skills and speech, plus improvements in mental health and quality of life for adults. Research has also observed that these benefits increase with earlier treatment. In 2012, consensus guidelines for GH therapy in PWS were produced by 43 international experts concluding that GH treatment should be considered for all patients with genetically confirmed PWS.

Somatropin (human growth hormone) was initially funded for PWS in New Zealand with restrictive access criteria which have gradually widened. Since January 2017, funded Somatropin can now be prescribed from 6 months old without a need for the collection of growth data. As benefits increase with earlier treatment, we recommend parents discuss growth hormone treatment with their endocrinologist as soon as possible, because of the time needed for the various referrals that need to take place prior to starting treatment. As a safety precaution, a sleep study should be undertaken and if OSA (obstructive sleep apnoea) is observed, a referral needs to be made to a respiratory physician or ENT for assessment and possible removal of tonsils and adenoids before starting GHT. (PHARMAC require a sleep study or overnight oximetry, but a sleep study is more thorough.) For children under 2 years, PHARMAC also require an upper airway assessment prior to starting treatment and at 6-12 weeks following treatment initiation. We would recommend a follow up sleep study for all patients after starting GH treatment. Before starting GHT, you will also need an appointment with a specialist nurse who demonstrates how to administer treatment. If safety checks and a nurse demonstration can be completed prior to 6 months, parents may wish to consider self-funding earlier treatment as the cost of growth hormone treatment has greatly reduced recently.

The brand of Somatropin currently used in New Zealand is Omnitrope. GHT is given daily before bedtime using an injection pen which is child and parent friendly. Endocrinologists continue to see children at three monthly intervals and will monitor growth, weight and regular blood test results. At the time of writing, special authority for funded GH treatment in New Zealand is renewed 12 monthly until a bone age of 14 years girls / 16 years boys is reached, providing growth criteria are met. The PWSA(NZ) continues to appeal to PHARMAC asking that changes are made to extend treatment time further and to remove the remaining growth criteria.

Analysis of data shows GHT is a safe treatment for PWS with minimal reported side effects. There has been concern of a possible association between GHT, sleep abnormalities and sudden death, however, recent studies show that with the development of respiratory muscle, GH therapy actually improves oxygenation and cardiovascular function during sleep in patients with PWS. (Sleep abnormalities are common and well documented in PWS, including central sleep apnoea which is common in infancy).

Lymphoid hyperplasia (increase in lymph node cells) may obstruct breathing and is related to high levels of IGF-I (Insulin-like Growth Factor-1 which the body produces in response to GHT), but research has shown that GH treatment does not change the prevalence or severity of obstructive sleep apnoea. As a result of this possible concern, the GH consensus guidelines recommend that for the paediatric age range, IGF-I levels should be maintained within the upper part of normal range. Prerequisites of GH treatment in New Zealand include there being no evidence of type II diabetes or uncontrolled obesity and tests for obstructive sleep disorder are performed prior to and during treatment. If obstructive sleep apnoea is observed, treatment is necessary before starting GHT, which means an adeno-tonsillectomy is usually required. During GH treatment, IGF-1 levels are closely monitored by endocrinologists. Studies have found that upper respiratory infections during the initiation phase of GH therapy can cause breathing problems in young children with PWS and whilst there is still some uncertainty about whether GH was responsible for worsening respiratory symptoms, some doctors advocate monitoring with several nights of pulse oximetry during upper respiratory infections or briefly pausing treatment.  In conclusion, close monitoring of IGF-1 levels, breathing and sleep abnormalities is recommended throughout GH treatment and especially during respiratory illness.

If you require more information about GHT for PWS, we recommend reading this clear and comprehensive book ‘Growth Hormone and Prader-Willi Syndrome’, published by PWSA USA.

There is an increasing body of research which demonstrates the benefits of continued Growth Hormone Therapy for maintaining an improvement in body composition and exercise capacity. Some of the largest studies being a multi-centre trial in the USA (Mogul et al, 2008), the Scandinavian study, 2012, and the latest compelling evidence from a study of 27 adults over 2 years in a double-blind, placebo-controlled, cross-over trial by Kuppens et al, 2016. There are also some studies which have revealed detrimental effects of stopping treatment, notably Butler et al, 2013; a study by Oto et al, 2014, which evaluated 14 patients and found that BMI significantly increased at 6, 12,18 and 24 months after cessation of GH therapy, and Koizumi et al, 2018, who noted significant, rapid increases in visceral adipose tissue and LDL cholesterol levels. In addition to body composition benefits, studies have also noted benefits for adults in the areas of cognition, behaviour, mental health and quality of life. Without GHT, symptoms of adult GH deficiency may develop, such as fatigue, depression and osteoporosis. These symptoms can also be exacerbated by a deficiency of sex hormones.