Sequential measurements of IGF-I serum concentrations in adolescents with Laron syndrome treated with recombinant human IGF-I (rhIGF-I).

Abstract

Background Recombinant human insulin-like growth factor 1 (rhIGF-I) has been approved as an orphan drug for the treatment of growth failure in children and adolescents with severe primary IGF-I deficiency (SPIGFD) with little pharmacokinetic data available. Therefore, sequential measurements of serum IGF-I, glucose, potassium, insulin and cortisol were performed in patients treated with rhIGF-I to evaluate their significance in safety and efficacy. Methods Repetitive blood samples were taken after meals before and 30, 60, 120, 180 and 360 min after rhIGF-I injections in two male patients with Laron syndrome at times of dose adjustments. Results Maximal IGF-I concentrations were observed 2 h after injections (495 ng/mL) and concentrations were still higher 6 h after injections than at baseline (303 ng/mL vs. 137 ng/mL). Thirteen percent of all and 33% of maximum IGF-I concentrations were greater than +2 standard deviation score (SDS) calculated for bone age (BA) (IGF-I SDS BA) rather than chronological age (CA) as BA was significantly delayed to CA by 3.2 years (p=0.0007). Height velocities correlated with individual maximum IGF-I SDS BA (ρ=0.735; p<0.0001). Serum insulin, cortisol and glucose did not correlate with IGF-I concentrations, but serum potassium showed a negative correlation (ρ=-0.364; p<0.0001) with IGF-I concentrations. Conclusions Sequential measurements of serum IGF-I, glucose and potassium in patients with Laron syndrome may aid in optimizing and individualizing rhIGF-I treatment. IGF-I concentrations should be referenced according to BA which better reflects the biological age. The inverse correlation of IGF-I and serum potassium concentrations after injections of rhIGF-I has not been reported before and warrants further consideration.

• Authors: Thomas Breil, Carolin Kneppo, Markus Bettendorf, German IGF-I Deficiency Study Group, Hermann L Müller, Klaus Kapelari, Dirk Schnabel, Joachim Woelfle
• Journal: Journal of pediatric endocrinology & metabolism : JPEM (J Pediatr Endocrinol Metab) Vol. 31 Issue 8 Pg. 895-902 (Aug 28 2018) ISSN: 2191-0251 [Electronic] Germany
• PMID: 29995632 (Publication Type: Journal Article)

Chemical References

• Biomarkers
• Blood Glucose
• IGF1 protein, human
• Insulin
• Recombinant Proteins
• Insulin-Like Growth Factor I

Topics

• Adolescent
• Adult
• Biomarkers (blood)
• Blood Glucose (analysis)
• Child
• Follow-Up Studies
• Growth Disorders (blood, drug therapy, pathology)
• Hearing Loss, Sensorineural (blood, drug therapy, pathology)
• Humans
• Insulin (blood)
• Insulin-Like Growth Factor I (administration & dosage, analysis, deficiency)
• Laron Syndrome (blood, drug therapy, pathology)
• Male
• Prognosis
• Recombinant Proteins (administration & dosage)
• Young Adult