Iron status of children with short stature during accelerated growth due to growth hormone treatment.

We determined the influence of human growth hormone (hGH) treatment on blood soluble transferrin receptor (sTfR) in 35 children with short stature. Whereas the serum concentration of ferritin decreased from 29.6 micrograms/l to 19.7 micrograms/l, and that of transferrin increased from 2.9 g/l to 3.2 g/l during 6 months (p < 0.001), only a minimum rise in the sTfR concentration was observed (7.12 +/- 0.20 mg/l vs 7.51 +/- 0.19 mg/l, p = 0.025). The prevalence of anaemia or microcytosis did not increase. Most of the changes in serum ferritin and transferrin concentrations occurred during the first week. The study demonstrates that rapid body growth per se does not affect the sTfR concentration, but it may affect the serum transferrin and ferritin concentrations. Alternatively, GH may have a specific effect on serum ferritin and transferrin concentrations.

Collagen formation and degradation increase during growth hormone therapy in children.

A comprehensive set of serum markers of collagen turnover and growth was investigated in a longitudinal study of short children during growth induced by growth hormone (hGH) treatment. The study comprised 18 prepubertal children with short stature who had no other current illness or continuous medication. The growth rates and endogenous GH secretions covered a continuum from subnormal to normal. Before treatment, the concentrations of carboxyterminal propeptide of type I procollagen (PICP), reflecting type I collagen formation, of carboxyterminal telopeptide of type I collagen (ICTP), a degradation product of type I collagen, of amino-terminal propeptide of type III procollagen (PIIINP), a marker for type III collagen formation, of alkaline phosphatase (AP), and of insulin-like growth factor binding protein-3 (IGFBP-3) were within the lower limits of normal. The median IGF-I concentration was lower than the reference. One week after the start of treatment, the serum concentrations of ICTP, PIIINP, and osteocalcin (OC), and the increments in ICTP, PIIINP, and IGF binding protein-3 (IGFBP-3) correlated with the subsequent height velocity. During the 12-month treatment, all markers were higher than those of age-matched references, but only the three collagen markers paralleled the changes in height velocity. In molar concentrations, ICTP increased less than PICP. Throughout the study period, the serum level of ICTP correlated with that of PIIINP, but not with that of PICP. The findings suggest that during hGH treatment, linear body growth is closely associated with collagen formation and degradation.

Hemoglobin level is linked to growth hormone-dependent proteins in short children.

Erythropoiesis was investigated in 32 children wih short stature and in eight children with skeletal dysplasia by studying blood hemoglobin in relation to growth and to serum concentrations of insulin-like growth factor I (IGF-I), IGF binding protein-3 (IGFBP-3), and erythropoietin (EPO) before, during, and after 12 months of recombinant human growth hormone (GH) treatment. Blood hemoglobin concentration was positively correlated with relative body height and with serum IGF-I and IGFBP-3 levels (P = .001 to .02), but not with the concentrations of EPO. The normal age-dependency of hemoglobin was lacking. Hemoglobin levels and their responses to GH treatment were similar in the patients with GH deficiency and those with normal GH secretion. Treatment with GH accelerated growth and elevated the concentrations of hemoglobin, IGF-I, and IGFBP-3. In the eight patients with skeletal dysplasia, body mass increased similarly, but gain in height was less than in the other patients, and the increase in hemoglobin was markedly pronounced. In this group, the correlations between hemoglobin, IGF-I, and IGFBP-3 were extremely close (r = 0.80 to 0.85, P = .031 to .008). These findings are in accord with earlier observations from in vitro and animal studies, and suggest that the GH-IGF axis is involved in the physiologic elevation of hemoglobin levels during childhood.

Growth delay after liver transplantation in childhood: studies of underlying mechanisms.

After liver transplantation in children, growth is often impaired, but the underlying mechanisms are unknown. Glucocorticoids used for immunosuppression are believed to be partly responsible. After renal transplantation in children, reduced growth hormone (GH) secretion and increased serum insulin-like growth factor-binding protein-3 (IGFBP-3) levels have been reported. We attempted to find endocrine factors predicting growth in 18 prepubertal children followed for more than 1 y (mean 2.4 y) after liver transplantation. Spontaneous and stimulated GH secretion, serum IGF-I, IGFBP-3 concentrations, and endogenous cortisol production were measured. GH secretion was reduced in only two patients. Serum IGF-I concentration was normal, but serum IGFBP-3 was elevated or 1 SD above the mean for age in 62% of the patients. Endogenous cortisol production was reduced in most patients during the first year and improved later in only a few. Growth velocity after transplantation did not correlate with GH secretion, serum IGF-I or IGFBP-3 concentration, or with methylprednisolone dose, but correlated positively with serum basal (rs = 0.44, p < 0.05) and stimulated (rs = 0.53, p < 0.005) cortisol concentration. In conclusion, after liver transplantation 1) the normal pulsatile character of nocturnal GH secretion is sustained, and the GH response to stimulation is reduced in only a few patients; 2) serum IGF-I concentrations are normal; 3) serum IGFBP-3 concentrations are elevated or in the upper part of the normal range in most patients; and 4) endogenous cortisol production is reduced in most patients and correlates positively with growth velocity.

Increases in hemoglobin concentration and iron needs in response to growth hormone treatment.

We studied 36 children with short stature during the initial 6 months of recombinant human growth hormone treatment and found an elevation in the mean concentration of hemoglobin (p < 0.001). The elevation was highest in the eight patients with bone dysplasia (p < 0.001). The mean concentration of serum ferritin decreased (p < 0.01) and that of serum transferrin increased (p < 0.001). The prevalence of iron deficiency increased from 6 patients (17%) with initial deficiency to 20 (56%) patients after therapy, indicating that iron supplementation should be considered in children treated with recombinant human growth hormone.