Constancy of somatomedin response to growth hormone treatment of hypopituitary dwarfism, and lack of correlation with growth rate

The correlation between acute and chronic somatomedin (SM) response to hGH treatment of hypopituitary dwarfism and the value of SM levels in predicting growth rates were investigated in 20 children with GH deficiency. Plasma samples for SM determinations were obtained before treatment, 12-14 h after each of 4 daily injections of hGH (0.1 U/kg) and after 6 months of hGH (0.1 U/kg 3 times per week). Mean plasma SM-C levels by placental membrane radioreceptor assay rose from 0.39 ± 0.05 U/ml (mean ± SEM) on day 1 to 1.18 ± 0.14 U/ml on day 5 and measured 0.95 ± 0.12 U/ml at 6 months. By RIA, mean plasma SM-C levels rose from 0.19 ± 0.03 U/ml on day 1 to 0.82 ± 0.11 U/ml on day 5 and measured 0.79 ± 0.11 U/ml at 6 months. However, individual SM responses to acute and chronic hGH treatment were highly variable, with 7 children raising SM-C levels above 1 U/ml (RIA) by day 5, while 3 children maintained SM levels less than 0.1 U/ml. The latter 3 had persistently low SM levels at 6 months (≤0.20 U/ml), despite good interval growth. In all, the acute SM response to hGH was highly predictive of SM levels during chronic hGH therapy: day 5 vs. 6-month SM-C, r = 0.80, P < 0.001. Although the mean annual growth rate increased significantly with hGH treatment (3.6 ± 0.1 cm/yr before treatment and 6.7 ± 0.6 cm/yr during the first year of hGH), no correlation was observed between growth rate and baseline, acute or chronic SM levels. This study demonstrates that 1) the acute SM-C response to hGH accurately predicts chronic SM-C levels; 2) SM-C responses to hGH therapy remain constant despite duration of treatment and changes in growth rate; 3) the SM-C response to hGH is, at least in part, age dependent; and 4) neither baseline nor hGH-stimulated SM-C levels correlate with growth response in hypopituitary dwarfs.