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IGF-1 Levels, Complex Formation, and IGF Bioactivity in Growth Hormone-Treated Children With Prader-Willi Syndrome
N E Bakker1, J van Doorn1, J S Renes1
1Dutch Growth Research Foundation (N.E.B., A.C.S.H.-K.), 3016 AH Rotterdam, The Netherlands; Department of Pediatrics (N.E.B., J.S.R., A.C.S.H.-K.), Subdivision of Endocrinology, Erasmus Medical Center/Sophia Children's Hospital, 3000 DR Rotterdam, The Netherlands; and Department of Clinical Chemistry and Haematology (J.v.D., G.H.D.), Laboratory of Endocrinology and Department of Medical Genetics, Section of Metabolic Diseases, University Medical Center Utrecht, 3508 GA Utrecht, The Netherlands.
In Prader-Willi syndrome (PWS) patients on growth hormone (GH) therapy, high IGF-1 levels are common but do not reflect bioactivity. IGF-1 levels are not a reliable indicator for GH dosing in PWS children.
Area of Science:
- Endocrinology
- Pediatrics
- Metabolic Disorders
Background:
- Children with Prader-Willi syndrome (PWS) often show high serum insulin-like growth factor 1 (IGF-1) levels during standard growth hormone (GH) treatment.
- Lowering GH dosage to manage high IGF-1 levels can negatively impact body composition in PWS children.
Purpose of the Study:
- To evaluate serum IGF-1, IGF binding protein 3 (IGFBP-3), and acid-labile subunit (ALS) levels in GH-treated PWS children.
- To assess IGF-1 complex formation and IGF bioactivity in this cohort.
- To determine the correlation between IGF-1 levels and IGF bioactivity in PWS.
Main Methods:
- Cross-sectional study of 40 GH-treated PWS children and 41 healthy controls from a Dutch PWS cohort.
- Measurement of serum IGF-1, IGFBP-3, and ALS levels.
- Assessment of IGF-1 complex formation and IGF bioactivity using IGF-1 receptor kinase activation assay.
Main Results:
- GH-treated PWS children had significantly higher serum IGF-1, IGFBP-3, and ALS levels compared to controls.
- Most serum IGF-1 in PWS children was sequestered in the 150-kDa ternary complex with IGFBP-3 and ALS.
- Higher IGF bioactivity was observed in younger GH-treated PWS children, but not in older ones. The proportion of IGF bioactivity was lower in PWS children than controls.
- Serum immunoreactive IGF-1 levels did not correlate with IGF bioactivity in GH-treated PWS children, unlike in healthy controls.
Conclusions:
- In GH-treated PWS children, serum IGF-1 is largely bound within the 150-kDa complex, limiting its bioactivity.
- IGF bioactivity varies significantly and is not consistently elevated in all GH-treated PWS children.
- Serum immunoreactive IGF-1 levels are an unreliable marker for guiding GH dosage in PWS due to a disrupted correlation with IGF bioactivity.
