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

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.

Effects of Growth Hormone on Growth, Insulin Resistance and Related Hormones (Ghrelin, Leptin and Adiponectin) in Turner Syndrome

“…Short-term changes in serum leptin levels have been found to show correlation with height response [16, 17]. However, in our study, although IGF-I increased and leptin decreased on GH therapy, there were no correlations between changes in leptin and IGF-I and change in height.…”

“…In the study by Tillmann et al [17] leptin levels decreased in GH-deficient children on GH therapy and not in non-GH-deficient children. In the study by Kriström et al [16] the marked decrease in leptin levels on GH therapy was evident in the first 3 months in GH-deficient and non-GH-deficient children.…”

“…Leptin levels are known to correlate with adipose tissue mass [15]. Short-term changes in serum leptin levels have provided a metabolic marker for the growth response to GH treatment in both GH-deficient and non-GH-deficient patients [16, 17]. On the other hand, serum levels of adiponectin are low in obesity and correlate with insulin sensitivity, i.e.…”

Auxological and hormonal prognostic factors of growth hormone (GH) therapy effectiveness in children with GH deficiency, available before treatment

“…According to Kriström et al [26] 58% of the variation in the 1 st year growth response to GH therapy might be explained by serum levels of IGF-I and IGFBP-3 before treatment, and their increase during GH therapy. Conversely, Tillmann et al [27], as well as Lanes and Jakubowicz [28] did not confirm any relationship between HV during GH therapy and IGF-I and IGFBP-3 concentrations. In 2005, Ranke et al [29] reported a negative correlation between HV in the initial phase of GH treatment and IGF-I SDS before GH therapy, however with no correlation between HV during the therapy and the increase of IGF-I secretion.…”

Serum IGF-I and IGFBP-3 Levels of Turkish Children during Childhood and Adolescence: Establishment of Reference Ranges with Emphasis on Puberty

“…The determination of IGF-I and IGFBP-3 serum levels has been widely used as screening parameters in the evaluation of growth disorders. In addition to diagnosis of GH deficiency or GH excess, serum levels of IGF-I and IGFBP-3 are used for monitoring the therapy in both conditions [11,12,13,14]. …”