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Objective: The aim of this study was to follow auxological parameters and their relationship to serum growth hormone-binding protein (GHBP) and leptin levels in children with acute lymphoblastic leukemia (ALL). Design and methods: In total, 26 prepubertal children with ALL were studied. We report these data at the time of the clinical diagnosis (n 26) and at 6 (n 21), 12 (n 21), 18 (n 21), 24 (n 20), 30 (n 16) and 36 months (n 16) after beginning treatment. Results: Serum GHBP levels decreased during the ®rst 18 months and returned to normal when therapy was withdrawn. Height SDS increased at 24 months after diagnosis. Weight and the upper arm circumference had increased 6 months after chemotherapy withdrawal, whereas tricipital and subscapular skinfolds had increased both at 6 months after diagnosis and 6 months after therapy had stopped. Therefore, the tendency to become overweight is both an early and a late side-effect of anti-leukemia therapy. A signi®cant positive correlation was found between serum leptin levels and every nutritional anthropometric parameter, with body mass index having the best relationship. However, serum GHBP levels were only correlated with BMI at the end of the study. No correlation was found between leptin and GHBP. Conclusions: In children with ALL, linear growth is compromised during the acute phase of their illness and therapy; this is probably secondary to a state of partial and transient GH insensitivity. These patients tend to become obese after therapy withdrawal, with leptin being an excellent nutritional marker.

Insulin-like growth factor (IGF)-binding protein-2 (IGFBP-2) is altered in different diseases and might be used as an indication of its severity. The aims of our study were to investigate: (1) the developmental pattern of the serum IGFBP-2 concentration at birth and during childhood and adolescence; (2) whether the serum IGFBP-2 level could be a marker for the diagnosis and evolution of diseases where the growth hormone (GH)-IGF axis is altered, and (3) whether this binding protein shows a relationship with IGF-I, its free fraction, IGFBP-1 and -3. We report reference values for 55 normal full-term newborns and 221 normal children who were divided into 5 groups according to their Tanner stage. Serum levels were higher in newborns when compared with Tanner stages I–V (p < 0.001, ANOVA), with no further changes throughout development. Furthermore, we studied IGFBP-2 levels in 24 children with congenital GH deficiency (GHD), 26 with acute lymphoblastic leukemia (ALL), 75 obese children, and 60 girls with anorexia nervosa (AN) at diagnosis and during a follow-up period. IGFBP-2 at diagnosis was increased in GHD, ALL and AN, and decreased in obesity (p < 0.05, ANOVA). During the follow-up, IGFBP-2 concentrations tended to normalize. IGFBP-2 correlated positively with IGFBP-1 and negatively with IGF-I and IGFBP-3 in normal subjects and at diagnosis of the pathologies studied. Although IGFBP-2 functions are not well understood, these results suggest a possible role for this protein in diseases where the GH-IGF axis is altered.

Insulin-like growth factors (IGFs) circulate in plasma as part of a 150-kD complex that also contains IGF-binding protein-3 (IGFBP-3), a protein that binds IGF-I and IGF-II with high affinity, and an acid-labile subunit (ALS) that does not directly bind IGFs. Because the ALS assay methods currently being used are relatively new, there is a need for updated normative reference data. We report the normative data in 17 preterm infants (10 males and 7 females), 30 normal full-term newborns (15 males and 15 females) and 150 normal children who where divided into 5 groups according to their Tanner stage (15 males and 15 females per group). Serum levels of total and free ALS were significantly lower in premature infants than in full-term newborns, but all newborns had significantly lower levels than Tanner stage-I children (p < 0.001, ANOVA). A significant increase was seen between Tanner stages I–III in both sexes (p < 0.001, ANOVA). No differences were found between sexes at any developmental age studied. Significant correlations (p < 0.001) were seen between total and free ALS concentrations and IGF-I (r = 0.50 and 0.60, respectively), free IGF-I (r = 0.37 and 0.36), IGF-II (r = 0.37 and 0.27), IGFBP-1 (r = –0.48 and –0.49), IGFBP-2 (r = –0.44 and –0.51) and IGFBP-3 (r = 0.67 and 0.59) at all Tanner stages. However, no correlation was found with IGFBP-1, -2 or -3 levels at birth. This study shows normal values in a population of preterm infants and healthy Spanish newborns and subjects of both sexes at all stages of pubertal development and indicate the different relationships between the components of the IGF system during intra- and extrauterine life.

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