Predictive diagnostic study on the short-term metabolic effects of recombinant human Growth Hormone treatment in growth hormone deficiency and small for gestational age children.

Short stature is a frequently seen problem for the paediatric endocrinologist.
As the most common endocrine cause the diagnosis growth hormone deficiency
(GHD) is stated. To diagnose GHD is troublesome, because of the paucity of
biological endpoints. Momentarily, GHD is confirmed in children by means of
growth hormone provocation tests, but the outcome of these endocrine tests is
not discriminative and does not adequately predict the effect of therapy on
growth. Besides its growth-promoting effect, growth hormone (GH) also
influences metabolism. The changes in metabolism might be useful as a predictor
of the growth effect.
There seems to be an association between the disturbance of the growth hormone
axis and several features of the metabolic syndrome (MS). The MS is
characterized as a cluster of metabolic abnormalities that strongly increase
the risk of cardiovascular disease and type II diabetes mellitus in adulthood.
It is known that both GH and insulin-like growth factor-I (IGF-I) reduces these
cardiovascular risk factors and has beneficial effects on body composition by
reducing fat mass and increasing muscle mass (1). Beside the GHD children also
children born small for gestational age (SGA) seem to benefit from rhGH
treatment.

The primary objective of this study is to assess the relation between the short
term metabolic changes after start of rhGH therapy and the long term change in
height SDS after one year of treatment. Secondly, we want to assess the effects
of GH on metabolic risk parameters which are typical parameters for the
metabolic syndrome in adults.

The study design is a predictive diagnostic study monitoring the metabolic
effects and efficacy of rhGH in GHD and SGA subjects. Total body water (TBW),
total energy expenditure (TEE), basal metabolic rate (BMR) and physical
activity level (PAL) measurements are performed over a 2-wk period using the
doubly labeled water (DLW) method before and during GH treatment. Markers of
metabolic risk factors will be determined during routine blood controls.
Baseline characteristics of growth patterns, blood pressure, BMI and waist
circumference are collected every three months during routine controls.
Furthermore, the measurements will be linked with the anthropometric parameters
of each individual assembling a prognostic growth profile, therefore the
children will be followed during one year of treatment to evaluate the change
in height standard deviation score (SDS).

All subjects receive recombinant human (rh)GH in accordance with international
guidelines.

Before the start of the study, subjects will be screened for underlying growth
pathology accordingly the Dutch Growth Research Foundation guidelines ,
including growth hormone test. When enrolled in the study, rhGH treatment will
be started. All visits are linked with the routine visit controls accordingly
to the guidelines, except the visit before start GH treatment and the six week
visit. Throughout these visits, routine blood controls are used for determining
metabolic risk markers, no extra blood controls are used. The total amount of
extra drawn blood would be maximum 10 ml. The risks of rhGH treatment are given
in the prescribing information, further are those of the doubly labeled water
(DLW) and Ventilated Hood (VH) method, which are none.