Constructing an Insulin-Like Growth Factor-based Prediction Model
Constructing an Insulin-Like Growth Factor-based Prediction Model
Serum insulin-like growth factor-I (IGF-I) measurements have been shown to correlate well
 with growth hormone action and effect, and recent data show that serum IGF-I may be related
 to safety and efficacy of growth hormone (GH) treatment in patients. Some studies indicate
 that high IGF-I levels are associated with increased cancer risk, and low IGF-I levels are
 associated with increased risk for cardiovascular disease. Studies in children also show that
 the serum IGF-I level is correlated with the change in height score achieved (that is, the
 higher the IGF-I level, the greater the gain in height). Pediatric endocrinologists have
 therefore begun to use serum IGF-I levels, in addition to growth rate and weight gain, to
 adjust the GH dose in treated children.

 Although monitoring of serum IGF-I levels is becoming standard of care in patients begin
 treated with GH, there are few guidelines regarding the actual logistics of adjusting GH
 dose. As serum IGF-I level has been linked to both safety and efficacy of GH treatment, the
 ideal practice would be to maintain serum IGF-I levels within a certain target range. The
 overall goal of our study is to construct a mathematical model which predicts the change in
 GH dose necessary to achieve a desired change in IGF-I level.

 Hypotheses to be tested by our study include the following: IGF-I measurement has a role in
 optimization of GH therapy; GH dose change to achieve IGF-I changes are predictable; and
 gender and puberty affect the relationship between dose change and target IGF-I changes.
The first phase of our study, previously approved by the UCLA IRB in August 2004, involved a
 retrospective chart review and collection of preexisting data. We analyzed charts of patients
 who underwent non-weight-based GH dose adjustments preceded and followed by a serum IGF-I
 level. Data collected included patient's age, gender, height, weight, linear height velocity,
 pubertal status, GH dose, IGF-I levels, disease condition (i.e., growth hormone deficiency,
 idiopathic short stature, small-for-gestational age) and recording of any adverse effects.
 Based on this data collected, we performed statistical analysis of the relationship between
 GH dose change and change in IGF-I level achieved, and have found that in prepubertal
 children, there is a significant relationship between the GH dose change and change in
 corresponding IGF-I level. We have subsequently constructed a mathematical prediction model
 that allows us to determine the GH dose change necessary to achieve a desired IGF-I level,
 and in this second phase of our study, we plan to apply this mathematical prediction model
 prospectively for guiding GH dose adjustments in prepubertal children being treated with GH
 therapy.

 Children being treated with GH are typically followed in the outpatient Endocrinology clinic
 every 3-4 months, and our practitioners have routinely been obtaining serum IGF-I levels (via
 venipuncture in the outpatient laboratory) for monitoring purposes. Validation of our GH dose
 change/IGF-I change prediction model will require assessment of sequential serum IGF-I level
 measurements immediately preceding a GH dose change, and again within 1-4 months following
 the GH dose change. We plan to continue our retrospective and ongoing analysis of patients
 who have paired values of GH dose adjustments preceded and followed by a serum IGF-I level,
 in order that we may continue to fine-tune our prediction model for optimizing GH dose
 adjustments.
Inclusion Criteria:

 -  Prepubertal patients,

 -  Male/female,

 -  Ages 3-14 yrs,

 -  Being treated with growth hormone for the conditions of growth hormone deficiency,
 idiopathic short stature, and small-for-gestational age with failure to catch up to
 the normal growth curve by age 2 years.

 Exclusion Criteria:

 -  Patients being treated with growth hormone for other conditions such as Turner
 syndrome, chronic renal failure, or Prader-Willi syndrome