Monitoring serum insulin‐like growth factor‐I (IGF‐I), IGF binding protein‐3 (IGFBP‐3), IGF‐I/IGFBP‐3 molar ratio and leptin during growth hormone treatment for disordered growth

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Abstract
OBJECTIVE: Serum IGF‐I levels are monitored during GH replacement treatment in adults with GH deficiency (GHD) to guide GH dose adjustment and to minimize occurrence of GH‐related side‐effects. This is not routine practice in children treated with GH. The aim of this study was to evaluate changes in (1) serum IGF‐I, IGFBP‐3 and IGF‐I/IGFBP‐3 molar ratio, and (2) serum leptin, an indirect marker of GH response, during the first year of GH treatment in children with disordered growth.DESIGN: An observational prospective longitudinal study with serial measurements at five time points during the first year of GH treatment was carried out. Each patient served as his/her own control.PATIENTS: The study included 31 patients, grouped as (1) GHD (n = 20) and (2) non‐GHD (Turner syndrome n = 7; Noonan syndrome n = 4), who had not previously received GH treatment.MEASUREMENTS: Serum IGF‐I, IGFBP‐3 and leptin levels were measured before treatment and after 6 weeks, 3 months, 6 months and 12 months of GH treatment, with a mean dose of 0.5 IU/kg/wk in GHD and 0.7 IU/kg/wk in non‐GHD groups. IGF‐I, IGFBP‐3 and the calculated IGF‐I/IGFBP‐3 molar ratio were expressed as SD scores using reference values from the local population.RESULTS: In the GHD group, IGF‐I SDS before treatment was lower compared with the non‐GHD (−5.4 ± 2.5 vs. −1.8 ± 1.0; P < 0.001). IGF‐I (−1.8 SDS ± 2.2) and IGFBP‐3 (−1.1 SDS ± 0.6) levels and their molar ratios were highest at 6 weeks and remained relatively constant thereafter. In the non‐GHD group, IGF‐I levels increased throughout the year and were maximum at 12 months (0.3 SDS ± 1.4) while IGFBP‐3 (1.1 SDS ± 0.9) and IGF‐I/IGFBP‐3 molar ratio peaked at 6 months. In both groups, IGF‐I SDS and IGF‐I/IGFBP‐3 during treatment correlated with the dose of GH expressed as IU/m2/week (r‐values 0.77 to 0.89; P = 0.005) but not as IU/kg/week. Serum leptin levels decreased significantly during GH treatment in the GHD (median before treatment 4.0 μg/l; median after 12 months treatment 2.4 μg/l; P = 0.02) but not the non‐GHD (median before treatment 3.0 μg/l; median after 12 months treatment 2.6 μg/l). In the GHD group, serum leptin before treatment correlated with 12 month change in height SDS (r = 0.70, P = 0.02).CONCLUSIONS: The pattern of IGF‐I, IGFBP‐3 and their molar ratio during the first year of GH treatment differed between the GHD and non‐GHD groups. Calculation of GH dose by surface area may be preferable to calculating by body weight. As a GH dose‐dependent increase in serum IGF‐I and IGF‐I/IGFBP‐3 may be associated with adverse effects, serum IGF‐I and IGFBP‐3 should be monitored routinely during long‐term GH treatment. Serum leptin was the only variable that correlated with first year growth response in GHD.

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