Growth Hormone Treatment and Prader-Willi Syndrome
Since the commercial release of recombinant human growth hormone (GH) in 1985, therapeutic
use of this medication has been studied in a variety of medical conditions and genetic
syndromes. Based on current medical knowledge, the Scientific Advisory Board of the
Prader-Willi Syndrome Association (USA) has drafted and approved this policy statement to
guide health care providers in the use of GH treatment in patients with Prader-Willi
Current considerations regarding the use of GH treatment in PWS can be divided into the
- Treatment of GH deficiency in children with PWS.
- Treatment of GH deficiency in adults with PWS.
- Treatment of body composition abnormalities in patients with PWS.
CHILDHOOD GROWTH HORMONE DEFICIENCY
As of this date, the United States Food and Drug Administration has approved
routine therapeutic use of GH for only 2 indications:
- Growth hormone deficiency in children.
- Growth failure associated with chronic renal failure in children.
Recent studies indicate that GH deficiency occurs frequently in children with PWS and
that treatment with GH is efficacious in improving the growth rate of these affected
children.\1 The Scientific Advisory Board recommends that routine clinical use of GH
treatment only be used in cases of documented GH deficiency. Moreover, the Board
recognizes that routine provocative GH testing is not ideal in children with PWS because:
(1) the results may be falsely low due to obesity, (2) the test procedure is associated
with a relatively high risk for morbidity and mortality, (3) different GH assays give
widely discrepant results, (4) the diagnostic boundary for a normal/abnormal GH result is
largely arbitrary, (5) there is lack of agreement on ideal testing protocols, and (6) the
test procedure is costly and requires a several hour period in the outpatient clinic or
The Board agrees with the recent recommendations of an international panel of pediatric
endocrinologists \2 that the diagnosis of childhood GH deficiency be based on a
combination of auxological and biochemical criteria:
- Short stature.
- Abnormally low height velocity.
- Abnormally low serum levels of insulin-like growth factor-I (IGF-I) and/or IGF-binding
- Absence of other conditions which may account for 1-3.
- Radiographic documentation of open epiphyseal growth plates.
The pros and cons of GH treatment should be thoroughly discussed with the child's
parents or guardians before making a decision to treat. Treatment should commence using
standard dose guidelines (~0.3 mg/kg/wk divided as a daily subcutaneous injection) with
careful monitoring of clinical status at 3-4 month intervals.
Standard GH treatment includes dose adjustments based on weight. However, there is some
evidence that lean mass is a better indicator of GH requirements. Therefore, the Board
recommends that the GH dose in children with PWS and GH deficiency be adjusted based on
clinical growth response rather than on strict weight-based criteria.
Once started, GH treatment may be continued until natural epiphyseal closure or when
the child has reached an acceptable adult height. Clinical monitoring should include
accurate height and weight measurements, physical examination and, if feasible, estimation
of body composition.
Children with PWS may be at increased risk for spinal curvature abnormalities,
including scoliosis and kyphosis. There is no evidence that GH itself causes these
abnormalities. However, such abnormalities often become more apparent and may worsen
during rapid growth. Therefore, children with PWS, whether or not they are treated with
GH, should receive a careful back examination at regular intervals. Radiographic studies
and orthopedic consultation should be obtained if clinically indicated. The decision to
treat or continue GH treatment in a child with spinal curvature abnormalities should be
made in consultation with an experienced orthopedic surgeon and after full discussion with
the child's parents or guardians.
Children with PWS are prone to developing obesity and its associated complications,
including glucose intolerance and non-insulin-dependent diabetes mellitus. GH is a
glucocounter-regulatory hormone. Therefore, children with PWS and GH deficiency should be
carefully monitored for signs and symptoms of glucose intolerance during GH treatment,
particularly if they are massively obese (e.g. >200% of ideal body weight) or have a
family history of diabetes mellitus. Routine biochemical screening tests may include a
fasting blood glucose, urine glucose dipstick or a total glycated hemoglobin measured by
boronate-affinity chromatography. If glucose intolerance or diabetes mellitus occurs, the
GH treatment should be stopped. If treatment is restarted, the dose of GH should be
ADULT GROWTH HORMONE DEFICIENCY
Recent studies indicate that adults with GH deficiency may benefit from replacement
therapy. However, the occurrence of GH deficiency in adults with PWS has not been well
documented. Furthermore, the therapeutic use of GH in adults regardless of clinical
condition has not yet been approved by the U.S. Food and Drug Administration.
BODY COMPOSITION ABNORMALITIES
Treatment with GH has been shown to positively affect nitrogen balance, increase lean body
mass and reduce body fat in several conditions. Moreover, treatment with GH may preserve
lean body mass \3 during caloric restriction. However, these effects have not been well
documented in individuals with PWS. Furthermore, the therapeutic use of GH in body
composition disorders other than those associated with childhood GH deficiency or
childhood chronic renal failure has not been approved by the U.S. Food and Drug
- Lee, P. D. K.: Endocrine and metabolic aspects of Prader-Willi syndrome. In
Greenswag, L. R., Alexander, R. C. (editors): Management of Prader-Willi Syndrome, second
edition. Springer-Verlag, New York, for the Prader-Willi Syndrome Association, 1995, pp.
- Rosenfeld, R. G., et al: Diagnostic controversy: The diagnosis of childhood
growth hormone deficiency revisited, Journal of Clinical Endocrinology and Metabolism 80,
- Angulo, M., et al: Growth hormone secretion and effects of growth hormone therapy
on growth velocity and weight gain in children with Prader-Willi syndrome. Journal of
Pediatric Endocrinology and Metabolism 9, 393-400, 1996.
Prader-Willi Syndrome Association (USA)
Scientific Advisory Board