Pediatric growth disorders treated with growth hormone (GH), including GH deficiency (GHD) and non-GHD conditions
Key Mechanisms
IGF-I and IGF-II regulate growth via IGF-binding proteins; bioactive IGF-I reflects IGF-I receptor activation and biological activity
Target Population
Children and adolescents receiving GH therapy for GHD and non-GHD conditions such as SGA, Turner syndrome, Prader-Willi syndrome, Noonan syndrome, and SHOX haploinsufficiency
Care Setting
Pediatric endocrinology clinics and specialized centers monitoring GH therapy
Key Highlights
Bioactive IGF-I increases with age and correlates positively with total IGF-I and IGF-I/IGFBP-3 molar ratio in healthy children.
In GH-treated children, bioactive IGF-I levels are generally within reference ranges, even when total IGF-I is supranormal.
Monitoring bioactive IGF-I may optimize GH dosing, especially in non-GHD subgroups where total IGF-I may not reflect efficacy.
Guideline-Based Recommendations
Diagnosis
Use pediatric, sex-specific reference ranges for bioactive IGF-I to interpret serum levels.
Assess Tanner stage and growth parameters alongside biochemical markers.
Management
Monitor serum total IGF-I levels to maintain values below the upper limit of the reference range during GH therapy.
Consider bioactive IGF-I measurement to guide GH dosing in specific patient subgroups, particularly non-GHD conditions.
Use total IGF-I as a safety parameter to avoid sustained supranormal levels.
Monitoring & Follow-up
Regularly measure serum total IGF-I and bioactive IGF-I during GH treatment.
Evaluate IGF-I/IGFBP-3 molar ratio and IGFBP-3 levels as complementary markers.
Monitor growth response in conjunction with biochemical markers.
Risks
Sustained elevated total IGF-I levels raise concerns about potential long-term risks including cancer, though current evidence is limited and mostly from adult cohorts.
Long-term surveillance studies in pediatric GH therapy are lacking; current data do not show increased mortality or cancer risk.
Patient & Prescribing Data
Children with GH deficiency and non-GHD short stature conditions undergoing recombinant human GH therapy
Total IGF-I levels may not reliably indicate efficacy in non-GHD conditions; bioactive IGF-I measurement can provide additional guidance for dose optimization and safety.
Clinical Best Practices
Establish and use sex-specific pediatric reference ranges for bioactive IGF-I.
Interpret total IGF-I and bioactive IGF-I levels together to assess GH therapy response.
Avoid relying solely on total IGF-I levels for dosing decisions in non-GHD patients.
by Lea Vilmann, Jakob Albrethsen, Jørgen Holm Petersen, Stine Agergaard Holmboe, Peter Christiansen, Katharina Maria Main, Line Cleemann, Kristian Horsman Hansen, Jan Frystyk, Casper P Hagen, Anders Juul
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