Growth Hormone Therapy

Growth hormone deficiency in PWS

(compiled by Linda Thornton)

It is possibly more appropriate in PWS to describe the lack of normal growth hormone production as growth hormone insufficiency, or growth failure.

There is considerable evidence that children with PWS have abnormalities in their GH and IGF-1 axis, even if their response to pharmacological stimulation of GH is "normal", implicating neurosecretory dysfunction in the phenotype of PWS. It has been suggested "that the response of GH secretion to nonpharmacological stimulation represents a more physiological investigation into proposed disturbances in secretory mechanism. Thus it has been found that in PWS the GH response to a dose of 1 ug/kg intravenous growth hormone releasing hormone (GHRH) was significantly less than that found in obese controls."

Growth hormone secretion has been shown to be abnormal in PWS and children with PWS are short in contrast to children with non-syndromal obesity. Their bone age is slightly retarded or normal. Studies of 315 patients with PWS show the weight of babies with PWS are below the normal average.

While during the first year the growth is nearly normal, short stature then becomes increasingly apparent. Between 3-13 years of age, the 50th percentile for height in PWS roughly equals the third percentile in healthy children indicating that growth in children with PWS slows down while they become obese, in contrast with healthy obese children. (Eiholzer et al, 2000)

Eiholzer contends that the "growth pattern in PWS considerably differs from that seen in non-syndromal obesity, bearing greater similarity to growth in GHD if some modification by overweight is taken into account." A further sign of extreme GH deficiency is also indicated in the typical presentation of short hands and feet, and the increased fat mass in PWS contrasted to nonsyndromal obesity (Eiholzer et al, 2000)

Growth Hormone Treatment in New Zealand

GH is now subsidised by PHARMAC under its own category, but patients must meet the following criteria:

ENTRY CRITERIA

In children with Prader-Willi Syndrome funding for growth hormone will be available where:

a diagnosis of PWS has been confirmed by genetic testing; and

growth velocity is <25th percentile for bone age over 12 months; and

growth velocity in patients under two years of age should be assessed over a minimum six month period from the age of 12 months, with at least three height or length measurements over this period demonstrating clear and consistent evidence of linear growth failure (growth velocity < 25th percentile); and

the bone age is <12 (girls) or <14 (boys); and

sleep studies have been performed and there is no obstructive sleep disorder requiring treatment, or if an obstructive sleep disorder is found, it has been adequately treated under the care of a sleep physician and/or ENT surgeon; and

there is no evidence of type II diabetes.

IGF-1 levels should be monitored to ensure the dose of growth hormone is not too high and, if IGF-1 levels are more than two standard deviations above the mean, the dose should be titrated down to bring IGF-1 levels closer to the normal range.

Patients approved for treatment with growth hormone should undergo a DEXA scan prior to starting treatment and on an annual basis during treatment to better analyse the effects of growth hormone and therefore provide evidence of its efficacy.

EXIT CRITERIA

Only one of the following criteria needs to be fulfilled to stop growth hormone therapy:

Growth velocity fails to increase by at least 2cm/yr following at least a six month trial of growth hormone in those who do not have complete growth hormone deficiency

A growth velocity in the second and sebsequent years of treatment in non growth hormone deficient patients that consistently falls below the 50th percentile for age for children with Prader-Willi Syndrome.

Bone age of >14 yrs (female) or >16 years (male) and the growth velocity <2cm/yr as calculated over six months.

An increase in bone age that exceeds the increase in height age in non-growth hormone deficient patients with very delayed bone ages.

BMI increases by 0.5 SDS or more in one year.

A malignancy that develops after growth hormone therapy was commenced.

A serious adverse reaction or complication that either the patient's specialist of New Zealand Growth Hormone Committee considers is likely to be attributable to growth hormone treatment.