Do growth hormone (GH) serial sampling, insulin-like growth factor-I (IGF-I) or auxological measurements have an advantage over GH stimulation testing in predicting the linear growth response to GH therapy?

OBJECTIVE: To compare the relative utility of GH secretion via pharmacological stimulation, overnight serial sampling, IGF-I levels and auxological variables as predictors of change in height standard deviation score (ΔHt SDS) during GH treatment. DESIGN: A multicentre observational study. PATIENTS: Prepubertal children (n = 825)with idiopathic growth failure who were subsequently treated with GH were divided into two groups, based on their maximum GH response to pharmacological stimulation testing: (1) idiopathic GH deficiency (IGHD), defined by a maximum GH response < 10 μg/I (n = 300); and (2) idiopathic short stature (ISS), with a maximum GH response ≥ 10 μg/I (n = 525) (GH conversion factor: 3 IU = 1 mg). MEASUREMENTS: Overnight spontaneous GH secretion was measured in all patients. The following characteristics of spontaneous GH secretion were studied: maximum or peak GH, mean peak GH, number of GH peaks, pooled GH, mean GH, and approximate entropy of GH secretion. RESULTS: Although children with IGHD had lower indices of spontaneous GH secretion, there were no differences between IGHD and ISS groups in baseline Ht SDS, growth rate or IGF-I level. The dose and duration of GH therapy were similar. There was no statistically significant difference in the mean (± SD) change in Ht SDS (ΔHt SDS) in the two groups (IGHD 1.3 ± 0.9 and ISS 1.2 ± 0.8). Measures of spontaneous secretion, such as peak GH, mean of GH peaks, mean area under GH peaks, and mean GH, as well as IGF-I concentrations, were all statistically significantly correlated with ΔHt SDS in IGHD children (P < 0.0001). A significant correlation was also observed for pooled GH (P = 0.002) and approximate entropy (P = 0.01). Children with the most severe ISS (Ht SDS < -3.33) demonstrated a more disorganized pattern of GH secretion compared to children who were not as short (Ht SDS -2.33 to -1.64), as indicated by a higher approximate entropy (0.673 ± 0.193 vs. 0.607 ± 0.161, P < 0.004). This increased disorder in GH secretion was accompanied by lower IGF-I levels (104 ± 99 μg/I vs. 137 ± 74 μg/I, P< 0.001), even though pooled GH concentrations were indistinguishable between the two groups (2.2 ± 1.3 μg/I vs. 2.0 ± 1.0 μg/I). Children with IGHD demonstrated lower approximate entropy than did those with ISS (0.551 ± 0.235 vs. 0.631 ± 0.182, P < 0.0001). Duration of GH treatment, height deficit and genetic potential (midparental Ht SDS) were the most important variables influencing ΔHt SDS in children receiving GH therapy. Maximum stimulated GH, IGF-I and indices of spontaneous GH secretion also correlated with ΔHt SDS, but their relative importance varied among diagnostic groups. CONCLUSIONS: Patients with GH deficiency demonstrate a reduced capacity for GH secretion, while those with idiopathic short stature exhibit a more disorderly and less functional secretory pattern. Although effective in predicting a response to GH treatment in patients with severe GH deficiency, overnight serial sampling is less practical than other methods currently available. In addition, serial sampling was less useful as a predictor of growth response to exogenous GH in patients with idiopathic short stature.