Tracking and Cumulative Lifetime Exposure to IGF-I in 6459 Healthy Individuals and in SGA Children Treated With GH

• Published in: The journal of clinical endocrinology and metabolism Vol. 108; no. 3; pp. 642 - 652
• Main Authors: Kjaer, Anna Sophie L, Jensen, Rikke Beck, Petersen, Jørgen H, Linneberg, Allan, Kårhus, Line Lund, Henriksen, Louise Scheutz, Johannsen, Trine Holm, Main, Katharina M, Hoffman, Andrew R, Juul, Anders
• Format: Journal Article
• Language: English
• Published: US Oxford University Press 01-03-2023
• Subjects: Child; Children; Cross-Sectional Studies; Epidemiology; Female; Fetal Growth Retardation; Human Growth Hormone - therapeutic use; Humans; Infant, Newborn; Infant, Small for Gestational Age; Insulin-Like Growth Factor Binding Protein 3; Insulin-like growth factor I; Insulin-Like Growth Factor I - metabolism; Insulin-like growth factors; Longitudinal studies; Male; Medical research; Medicine, Experimental; Protein binding; Denmark; short stature; IGF-I; IGFBP-3; SGA; GH treatment
• ISSN: 0021-972X; 1945-7197
• DOI: 10.1210/clinem/dgac605

Abstract
Context
Supraphysiological serum insulin-like growth factor-I (IGF-I) concentrations have been a matter of concern in children treated with GH because high IGF-I levels were associated with risk of later disease in former epidemiological studies.
Objective
To determine whether a single IGF-I measurement reliably reflects lifetime IGF-I exposure we evaluated intraindividual longitudinal tracking of IGF-I and IGF-binding protein-3 (IGFBP-3) levels and we estimated cumulative lifetime exposure to IGF-I in healthy and GH-treated individuals.
Methods
We included 6459 healthy participants (cross-sectional = 5326; longitudinal = 1133) aged 0-76 years (9963 serum samples) and 9 patients born small-for-gestational-age (SGA) with 238 serum samples during GH treatment. Intraindividual tracking of IGF-I and IGFBP-3 (SD score [SDS]) was determined by intraclass correlation coefficients (ICCs). Cumulative lifetime IGF-I exposure was estimated by area under the curve of the predicted SDS trajectory from 0 to 76 years.
Results
For IGF-I (SDS), ICCs were 0.50 (95% CI, 0.47-0.53) for male and 0.53 (0.50-0.56) for female participants. Lifetime IGF-I exposure was significantly higher in female (mean 12 723 ± 3691 SD) than in male participants (12 563 ± 3393); P = 0.02. In SGA children, treatment with GH increased the lifetime exposure to IGF-I from 9512 ± 1889 to 11 271 ± 1689, corresponding to an increase in lifetime IGF-I trajectory from −0.89 SD ± 0.57 to −0.35 SD ± 0.49.
Conclusion
Because IGF-I and IGFBP-3 levels track throughout life, a single measurement reliably reflects lifetime exposure. GH therapy increased the lifetime exposure to IGF-I only slightly and it remained below the average lifetime exposure in the reference population.