OBJECTIVE: Serum IGF-I levels are monitored during
GH replacement treatment in adults with GH defi-
ciency (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 g/l; median after 12 months treatment 2.4 g/l; P = 0.02) but not the non-GHD (median before treatment 3.0 g/l; median after 12 months treatment 2.6 g/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 longterm
GH treatment. Serum leptin was the only variable
that correlated with first year growth response in
GHD
